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A Treatment Study Protocol for Participants 0-45 Years With Acute Lymphoblastic Leukaemia

Primary Purpose

Leukemia, Acute Lymphoblastic

Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Omitted Doxorubicin
Omitted Vincristine+Dexamethasone pulses
Inotuzumab Ozogamicin+Standard Maintenance Therapy
Imatinib
6-tioguanine+Standard Maintenance Therapy
Blinatumomab
Sponsored by
Mats Heyman
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia, Acute Lymphoblastic focused on measuring Leukemia, Acute Leukemia, ALL, ALLTogether, Leukaemia, Inotuzumab ozogamicin, Besponsa, ALLTogether1, Blinatumomab, Blincyto, 6-tioguanine, 6-thioguanine

Eligibility Criteria

0 Years - 45 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients newly diagnosed with T-lymphoblastic (T-cell) or B-lymphoblastic precursor (BCP) leukaemia (ALL) according to the WHO-classification of Tumours of Haematopoetic and Lymphoid Tissues (Revised 4th edition 2017) and with a diagnosis confirmed by an accredited laboratory at a participating paediatric oncology or adult haematology centre.
  • Age ≥ 0 days and < 46 years (one day before 46th birthday) at the time of diagnosis with the exception of infants with KMT2A-rearranged (KMT2A-r) BCP ALL.
  • Informed consent signed by the patient and/or parents/legal guardians according to country-specific age-related guidelines (http://www.ema.europa.eu/docs/en_GB/document_library/Other/2015/12/WC500199234.pdf ).
  • The ALL diagnosis should be confirmed by an accredited laboratory at a participating paediatric oncology or adult haematology centre.
  • The patient should be diagnosed and treated at a participating paediatric oncology or adult haematology centre in the participating countries.
  • The patient should be a resident in one of the participating countries on a permanent basis or should intend to settle in a participating country, for instance by an application for asylum. Patients who are visiting the country as tourists should not be included. However, returning expatriots with primary diagnosis abroad may be included if no treatment has been administered and the diagnostic procedures are repeated at a participating centre.
  • All women of childbearing potential (WOCBP) have to have a negative pregnancy test within 2 weeks prior to the start of treatment.
  • For each intervention/randomisation an additional set of inclusion-criteria is provided.

Exclusion Criteria:

  • Age < 365 days and KMT2A-rearranged (KMT2A-r) BCP-ALL (documented precence of a KMT2A-split by FISH and/or a KMT2A fusion transcript).
  • Age >45 years at diagnosis.
  • Patients with a previous malignant diagnosis (ALL as a second malignant neoplasm - SMN).
  • Relapse of ALL.
  • Patients with mature B-ALL (as defined by Surface Ig positivity or documented presence of one of the t(8;14), t(2;8), t(8;22) translocations and breakpoint as in B-ALL).
  • Patients with Ph-positive ALL (documented presence of t(9;22)(q34;q11) and/or of the BCR/ABL fusion transcript). These patients will be transferred to an adequate trial for t(9;22) if available.
  • ALL prone syndromes (e.g. Li-Fraumeni syndrome, germline ETV6 mutation), except for Down syndrome. Exploration for such ALL prone syndromes is not mandatory.
  • Treatment with systemic corticosteroids (>10mg/m2/day) for more than one week and/or other chemotherapeutic agents in a 4-week interval prior to diagnosis (pre-treatment).
  • Pre-existing contraindications to any treatment according to the ALLTogether protocol (constitutional or acquired disease prior to the diagnosis of ALL preventing adequate treatment).
  • Any other disease or condition, as determined by the investigator, which could interfere with the participation in the study according to the study protocol, or with the ability of the patients to cooperate and comply with the study procedures.
  • Women of childbearing potential who are pregnant at the time of diagnosis.
  • Women of childbearing potential and fertile men who are sexually active and are unwilling to use adequate contraception during therapy. Efficient birth control is required.
  • Female patients, who are breast-feeding.
  • Essential data missing from the registration of characteristics at diagnosis (in consultation with the protocol chair).
  • For each intervention/randomisation an additional set of exclusion-criteria is provided.

Sites / Locations

  • L'hôpital Universitaire des enfants Reine Fabiola (Huderf)Recruiting
  • Cliniques Universitaires Saint-Luc (UCL)Recruiting
  • University Hospital AntwerpRecruiting
  • University Hospital GhentRecruiting
  • University Hospital Leuven, Dept of PaediatricsRecruiting
  • CHC MontLégia, Boulevard Patience et Beaujonc 2Recruiting
  • CHR de la CitadelleRecruiting
  • Aalborg University Hospital, Dept of PaediatricsRecruiting
  • Aarhus University HospitalRecruiting
  • Aarhus University Hospital, Child and Adolescent HealthRecruiting
  • Rigshospitalet, Dept of HaematologyRecruiting
  • Rigshospitalet, Dept of PaediatricsRecruiting
  • Odense University Hospital, Dept of PaediatricsRecruiting
  • North Estonia Medical Centre, Dept of HaematologyRecruiting
  • Tallinn Children´s Hospital, Dept of PaediatricsRecruiting
  • Tartu University HospitalRecruiting
  • Helsinki University Hospital, Dept of HaematologyRecruiting
  • Helsinki University Hospital, Dept of PaediatricsRecruiting
  • Kuopio University Hospital, Dept of HaematologyRecruiting
  • Kuopio University Hospital, Dept of PaediatricsRecruiting
  • Oulu University Hospital, Dept of Haematology, Dept of MedicineRecruiting
  • Oulu University Hospital, Dept of PaediatricsRecruiting
  • Tampere University Hospital, Dept of HaematologyRecruiting
  • Tampere University Hospital, Dept of PaediatricsRecruiting
  • Turku University Hospital, Clinical Haematology and Stem Cell Transplantation UnitRecruiting
  • Turku University Hospital, Dept of PaediatricsRecruiting
  • CHU Amiens Groupe Hospitalier SudRecruiting
  • CHU AngersRecruiting
  • CHRU BesançonRecruiting
  • CHU Bordeaux - Groupe Hospitalier PellegrinRecruiting
  • CHRU Brest - MorvanRecruiting
  • Centre Hospitalier Universitaire CaenRecruiting
  • CHU Clermont-FerrandRecruiting
  • CHU Dijon Hôpital François MitterrandRecruiting
  • CHU de Grenoble site Nord - Hôpital Albert MichallonRecruiting
  • CHRU de Lille - Hôpital Jeanne de FlandreRecruiting
  • Hôpital de la mère et de l'enfantRecruiting
  • CHU de Lyon HCL - GH Est-Institut d'hématologie et d'oncologie pédiatrique IHOPRecruiting
  • CHU de Marseille - Hôpital de la TimoneRecruiting
  • CHU de Montpellier - Hôpital Arnaud de VilleneuveRecruiting
  • CHU Nantes-Hôpital enfant-adolescentRecruiting
  • CHU Nice - Hôpital l'Archet 2Recruiting
  • CHU Paris Saint LouisRecruiting
  • CHU Paris Armand TrousseauRecruiting
  • CHU Paris - Hôpital Robert DebréRecruiting
  • CHU PoitiersRecruiting
  • CHU Reims-American HospitalRecruiting
  • CHU Rennes - Hôpital sudRecruiting
  • CHU RouenRecruiting
  • CHU De La Réunion - Site Nord (Hôpital Félix GUYON)
  • CHU Saint Etienne Hôpital NordRecruiting
  • CHU Strasbourg -Hôpital de HautepierreRecruiting
  • CHU ToulouseRecruiting
  • CHRU Tours- Hôpital ClochevilleRecruiting
  • CHU de Nancy - Hôpital de Brabois EnfantRecruiting
  • Evangelisches Klinikum BethelRecruiting
  • Universitätsklinikum BonnRecruiting
  • Klinikum Bremen MitteRecruiting
  • Universitätsklinikum Hamburg-EppendorfRecruiting
  • HELIOS Klinikum KrefeldRecruiting
  • Universitätsmedizin MainzRecruiting
  • Landspitali University Hospital, Children's HospitalRecruiting
  • Our Lady's Children's Hospital
  • Children's Hospital, Affiliate of Vilnius University Hospital Santaros KlinikosRecruiting
  • Vilnius University Hospital Santaros Klinikos
  • University Medical Center Utrecht, Dept of Hematology
  • Princess Máxima Center for Pediatric OncologyRecruiting
  • University Medical Center UtrechtRecruiting
  • Haukeland University Hospital, Dept of HaematologyRecruiting
  • Haukeland University Hospital, Dept of PaediatricsRecruiting
  • Oslo University Hospital, Dept of HaematologyRecruiting
  • Oslo University Hospital, Dept of paediatric haemato- and oncologyRecruiting
  • Stavanger University Hospital, Dept of HaematologyRecruiting
  • University Hospital North Norway, Dept of HaematologyRecruiting
  • University Hospital of North Norway, Dept of PaediatricsRecruiting
  • St. Olavs University Hospital, Dept of PaediatricsRecruiting
  • St. Olavs University Hospital, Dept of HaematologyRecruiting
  • Centro Hospitalar e Universitário de Coimbra, EPE - Hospital Pediátrico de Coimbra
  • Instituto Português de Oncologia de Lisboa Francisco Gentil, EPERecruiting
  • Instituto Português de Oncologia do Porto Francisco Gentil, EPE
  • Sahlgrenska University Hospital, Section for Haematology and coagulationRecruiting
  • Sahlgrenska University Hospital, Dept of Paediatric Haematology and OncologyRecruiting
  • Linköping University Hospital, Dept of HaematologyRecruiting
  • Linköping University Hospital, Dept of PaediatricsRecruiting
  • Skåne University Hospital, Dept of HaematologyRecruiting
  • Skåne University Hospital, Dept of PaediatricsRecruiting
  • Karolinska University Hospital, Dept of Paediatric Oncology and HaematologyRecruiting
  • Karolinska University Hospital, Patient area HaematologyRecruiting
  • Norrland University Hospital, Dept of HaematologyRecruiting
  • Norrland University Hospital, Dept of PaediatricsRecruiting
  • Uppsala University Hospital, Dept of HaematologyRecruiting
  • Uppsala University Hospital, Dept of Paediatric Haematology and OncologyRecruiting
  • Örebro University Hospital, Section for HaematologyRecruiting
  • Aberdeen Royal Infirmary, Aberdeen
  • Royal Aberdeen Children's Hospital, Aberdeen
  • Royal Belfast Hospital for Sick Children, Belfast
  • Belfast City Hospital, Belfast
  • The Queen Elizabeth Hospital, BirminghamRecruiting
  • Birmingham Children's Hospital, BirminghamRecruiting
  • Bristol Royal Hospital for Children / Bristol Haematology and Oncology CentreRecruiting
  • Addenbrooke's Hospital, CambridgeRecruiting
  • Noah's Ark Children's Hospital for Wales, Cardiff
  • University Hospital of Wales, Cardiff
  • Ninewells Hospital, Dundee
  • Western General Hospital, Edinburgh
  • Royal Hospital for Children and Young People, EdinburghRecruiting
  • Beatson West of Scotland Cancer Centre, Glasgow
  • Royal Hospital for Children, GlasgowRecruiting
  • Leeds General Infirmary, LeedsRecruiting
  • Leeds St James University HospitalRecruiting
  • Leicester Royal Infirmary, LeicesterRecruiting
  • Alder Hey Children's Hospital, LiverpoolRecruiting
  • The Clatterbridge Cancer Centre NHS Foundation TrustRecruiting
  • University College London Hospital, LondonRecruiting
  • Great Ormond Street Hospital for Children, LondonRecruiting
  • King's College Hospital
  • St. Bartholomews HospitalRecruiting
  • Royal Manchester Children's Hospital, Manchester
  • The Christie NHS Foundation Trust (PTC)Recruiting
  • Royal Victoria Infirmary, NewcastleRecruiting
  • Freeman Hospital, Newcastle
  • Nottingham City Hospital, Nottingham
  • Nottingham Queen's Medical CentreRecruiting
  • Churchill Hospital, Oxford
  • John Radcliffe Hospital, OxfordRecruiting
  • Derriford HospitalRecruiting
  • Royal Hallamshire Hospital, Sheffield
  • Sheffield Children's Hospital, SheffieldRecruiting
  • Southampton General Hospital, SouthamptonRecruiting
  • Royal Stoke University Hospital, Stoke
  • Royal Marsden Hospital, SuttonRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm Type

No Intervention

Experimental

No Intervention

Experimental

No Intervention

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

R1 - SR standard arm

R1 - SR experimental arm

R2 - IR-low standard arm

R2 - IR-low experimental arm A

R3 - IR-high standard arm

R3-InO - IR-high experimental arm

ABL-class fusions intervention

R3-TEAM - IR-high experimental arm

ALLTogether1 DS Blinatumomab intervention

R2 - IR-low experimental arm B

Arm Description

Standard risk arm receiving standard treatment (Delayed Intensification including Doxorubicin).

Standard risk arm, receiving Delayed Intensification without Doxorubicin IV 3 x 30 mg/m2/dose.

Standard treatment with Delayed Intensification including Doxorubicin and Maintenance including Vincristine+Dexamethasone pulses.

Standard treatment with omission of Doxorubicin IV 3 x 30 mg/m2/dose in the Delayed Intensification phase.

Intermediate risk high arm receiving Standard Maintenance Therapy.

Inotuzumab IV 0,5 mg/m2, given on days 253, 260, 267 and on days 274, 281, 288 before start of Standard Maintenance Therapy.

Imatinib p.o. 340 mg/m2 given daily from day 15 or 30 (depending on age) to the end of therapy (week 106) in addition to Standard IR-high chemotherapy.

6-tioguanine p.o, 2,5-12,5 mg/m2, given daily in addition to Standard Maintenance Therapy.

Blinatumomab IV, 5 mcg/m2/day up to 28 mcg/day (detailed dosing in protocol) continous infusion. Two 28 day courses with a two week treatment free interval in between. Blinatumomab courses replace Consolidation 1 and Consolidation 2 in the standard protocol adapted for Down syndrome patients.

Standard treatment with omission of monthly pulses of Vincristine IV 1,5 mg/m2/dose and 5 days of Dexamethasone p.o. 6 mg/m2/day in the Maintenance Phase.

Outcomes

Primary Outcome Measures

Event-free survival (EFS) for the whole protocol
The primary endpoint for the whole protocol (compared with the legacy protocols of the participating study-groups forming the consortium) is event-free survival (EFS) - as defined in the protocol.
Event-free survival (EFS) for the TKI intervention
The primary endpoint for the TKI intervention is event-free survival (EFS) - as defined in the protocol, from the start of TKI until event or end of follow-up
Disease-free survival (DFS) R1 + R2
The primary endpoint for Randomisation 1 and 2 is disease-free survival (DFS) - as defined in the protocol counting from the time of randomisation
Disease-free survival (DFS) R3
The primary endpoint for Randomisation 3 and the ABL-class fusion intervention is disease-free survival (DFS) - as defined in the protocol counting from the time of randomisation (R3) and the start of TKI-therapy (ABL-class fusion intervention).
MRD response after 1 cycle of Blinatumomab
Fraction of patients with undetectable MRD ("Complete MRD response") at the end of one cycle of Blinatumomab (+/- 1 week)

Secondary Outcome Measures

Overall survival (OS) for the whole protocol
Overall survival defined as time from diagnosis to death or end of follow-up for surviving patients.
Overall survival (OS) for R1 + R2
Overall survival defined as time from randomisation to death or end of follow-up for surviving patients.
Overall survival (OS) for R3
Overall survival defined as time from randomisation to death or end of follow-up for surviving patients.
Overall survival (OS) for R3-TEAM associated with DNA-TG
Overall survival as defined above in relation to DNA-TG.
Overall survival (OS) for TKI
Overall survival defined as time from start of TKI to death or end of follow-up for surviving patients
Overall survival (OS) for ALLTogether1 DS
Overall survival defined as time from start of Blinatumomab to death or end of follow-up for surviving patients
Induction death
Fraction of patients who die as well as cumulative incidence of death before achieved complete remission (CR) within the time-frame described in the protocol
Resistant disease
Fraction of patients as well as cumulative incidence of resistant disease as described in the protocol. Induction death as competing risk.
Cumulative incidence of relapse for the whole protocol
Time from achieved complete remission until relapse as defined in the protocol or end of follow-up. Second malignancy, death in complete remission as competing events.
Cumulative incidence of relapse for R1 + R2
Time from randomisation until relapse as defined in the protocol or end of follow-up. Second malignancy, death in complete remission as competing events.
Cumulative incidence relapse for R3
Time from randomisation until relapse as defined in the protocol or end of follow-up. Second malignancy, death in complete remission as competing events.
Cumulative incidence relapse for R3-TEAM in association with DNA-TG
Cumulative incidence of relapse as defined for R3 in association with DNA-TG for R3-TEAM. Second malignancy, death in complete remission as competing events.
Cumulative incidence CD22 negative relapse for R3
Time from randomisation until relapse without expression of CD22 as defined in the protocol or end of follow-up. Second malignancy, death in complete remission and relapse with CD22 expression as competing events.
Cumulative incidence relapse for TKI
Time from start of TKI until relapse as defined in the protocol or end of follow-up. Second malignancy, death in complete remission as competing events.
Cumulative incidence relapse for ALLTogether1 DS
Time from start of Blinatumomab until relapse as defined in the protocol or end of follow-up. Second malignancy, death in complete remission as competing events.
Cumulative incidence of CD19 negative relapse for ALLTogether1 DS
Time from start of Blinatumomab until CD19 negative relapse as defined in the protocol or end of follow-up. Second malignancy, death in complete remission and CD19 positive relapse as competing events.
Cumulative incidence of second malignant neoplasm (SMN) for the whole protocol
Time from achieved complete remission until diagnosis of second malignant neoplasm as defined in the protocol or end of follow-up. Relapse and death in complete remission as competing events.
Cumulative incidence of second malignancy for R1+R2
Time from randomisation until diagnosis of second malignant neoplasm as defined in the protocol or end of follow-up. Relapse and death in complete remission as competing events.
Cumulative incidence of second malignancy for R3
Time from randomisation until diagnosis of second malignant neoplasm as defined in the protocol or end of follow-up. Relapse and death in complete remission as competing events.
Cumulative incidence of second malignancy for R3-TEAM in association with DNA-TG
Cumulative incidence of second malignancy as defined above for R3 in association with DNA-TG for R3-TEAM. Relapse and death in complete remission as competing events.
Cumulative incidence of second malignancy for TKI
Time from start of TKI until diagnosis of second malignant neoplasm as defined in the protocol or end of follow-up. Relapse and death in complete remission as competing events.
Cumulative incidence of second malignancy for ALLTogether1 DS
Time from start of Blinatumomab until diagnosis of second malignant neoplasm as defined in the protocol or end of follow-up. Relapse and death in complete remission as competing events.
Cumulative incidence of death in complete remission for the whole protocol
Time from achieved complete remission until death in complete remission as defined in the protocol or end of follow-up. Relapse and second malignant neoplasm as competing events.
Cumulative incidence of death in complete remission for R1+R2
Time from randomisation until death in complete remission as defined in the protocol or end of follow-up. Relapse and second malignant neoplasm as competing events.
Cumulative incidence of death in complete remission for R3
Time from randomisation until death in complete remission as defined in the protocol or end of follow-up. Relapse and second malignant neoplasm as competing events.
Cumulative incidence of death in complete remission for TKI
Time from start of TKI until death in complete remission as defined in the protocol or end of follow-up. Relapse and second malignant neoplasm as competing events.
Cumulative incidence of death in complete remission for ALLTogether1 DS
Time from start of Blinatumomab until death in complete remission as defined in the protocol or end of follow-up. Relapse and second malignant neoplasm as competing events.
Cumulative incidence of treatment-related mortality for the whole protocol
Time from diagnosis until death during induction, death in complete remission or death from second malignant neoplasm (if not related to SMN-treatment).
Cumulative incidence of treatment-related mortality R1+R2
Time from randomisation until death in complete remission or death from second malignant neoplasm (if not related to SMN-treatment).
Cumulative incidence of treatment-related mortality R3
Time from randomisation until death in complete remission or death from second malignant neoplasm (if not related to SMN-treatment).
Cumulative incidence of treatment-related mortality TKI
Time from start of TKI until death in complete remission or death from second malignant neoplasm (if not related to SMN-treatment).
Leukaemia specific mortality for the whole protocol
Time from diagnosis until death after resistant disease or relapse - as defined in the protocol.
Leukaemia specific mortality for R1+R2
Time from randomisation until death after relapse - as defined in the protocol.
Leukaemia specific mortality for R3
Time from randomisation until death after relapse - as defined in the protocol.
Leukaemia specific mortality for TKI
Time from start of TKI until death after relapse - as defined in the protocol.
Incidence of Adverse Events of Special Interest (AESIs) per treatment-phase in the whole protocol and TKI intervention
Cumulative incidence of 19 AESIs as defined in the protocol
Incidence of Adverse Events of Special Interest (AESIs) extra assessment (R1+R2)
Cumulative incidence of 4 additional AESIs as defined in the protocol
Incidence of Adverse Events of Special Interest (AESIs) extra assessment (R3)
Cumulative incidence of 3 additional AESIs as defined in the protocol
Incidence of Serious Adverse Events (SAEs) and Adverse Events (AEs) related to R3
Cumulative incidence of SAEs and AEs (with limitations) as defined in the protocol
Quantitative measures of toxicity R1+R2
Days: in hospital, with iv antibiotics, with iv analgesics, with iv nutritional support
Metabolic consequences of steroid exposure (R2)
Measurements of BMI
Association of Disease-free survival (DFS) with DNA-TG for R3-TEAM
Disease-free survival (DFS) - as defined above associated with DNA-TG.
Cumulative incidence of Sinusoidal Obstruction Syndrome (SOS) and Nodular Regenerative Hyperplasia (NRH) for R3-TEAM
Time from randomisation until diagnosis of SOS or NRH as defined in the protocol or end of follow-up.
Cumulative incidence of Osteonecrosis for R3-TEAM
Time from randomisation until diagnosis of osteonecrosis as defined in the protocol or end of follow-up.
Event-free survival (EFS) for ALLTogether1 DS
Event-free survival as defined in the protocol, from the start of Blinatumomab until death from any cause, relapse, second malignancy, protocol therapy failure (MRD>1% after 2 cycles blinatumomab and Augmented BFM consolidation) or end of follow-up.
Incidence of Blinatumomab refractory disease for ALLTogether1 DS
Incidence of progressive disease under Blinatumomab treatment or MRD ≥1% at the end of the 2nd cycle of Blinatumomab.
Incidence of Protocol Therapy Failure for ALLTogether1 DS
Incidence of patients who have MRD ≥1 % post 2 cycles of Blinatumomab followed by Augmented BFM consolidation, corresponding to original protocol day 99, or unchanged/increasing MRD during Augmented BFM consolidation corresponding to original protocol day 57.

Full Information

First Posted
March 5, 2020
Last Updated
August 31, 2023
Sponsor
Mats Heyman
Collaborators
The Swedish Research Council, The Swedish Childhood Cancer Foundation, Pfizer, Servier, NordForsk, Aamu Pediatric Cancer Foundation, German Society for Pediatric Oncology and Hematology GPOH gGmbH, Clinical Trial Center North (CTC North GmbH & Co. KG), Belgium Health Care Knowledge Centre, Karolinska Institutet, Cancer Research UK, Fundação Rui Osório de Castro, Acreditar - Associação de Pais e Amigos das Crianças com Cancro, Grupo Português De Leucemias Pediátricas, Amgen, Nova Laboratories Limited, Danish Child Cancer Foundation, Danish Cancer Society, The Novo Nordic Foundation, Assistance Publique - Hôpitaux de Paris, Direction Générale de l'Offre de Soins
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1. Study Identification

Unique Protocol Identification Number
NCT04307576
Brief Title
A Treatment Study Protocol for Participants 0-45 Years With Acute Lymphoblastic Leukaemia
Official Title
ALLTogether1 - A Treatment Study Protocol of the ALLTogether Consortium for Children and Young Adults (0-45 Years of Age) With Newly Diagnosed Acute Lymphoblastic Leukaemia (ALL)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 13, 2020 (Actual)
Primary Completion Date
June 30, 2027 (Anticipated)
Study Completion Date
June 30, 2032 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Mats Heyman
Collaborators
The Swedish Research Council, The Swedish Childhood Cancer Foundation, Pfizer, Servier, NordForsk, Aamu Pediatric Cancer Foundation, German Society for Pediatric Oncology and Hematology GPOH gGmbH, Clinical Trial Center North (CTC North GmbH & Co. KG), Belgium Health Care Knowledge Centre, Karolinska Institutet, Cancer Research UK, Fundação Rui Osório de Castro, Acreditar - Associação de Pais e Amigos das Crianças com Cancro, Grupo Português De Leucemias Pediátricas, Amgen, Nova Laboratories Limited, Danish Child Cancer Foundation, Danish Cancer Society, The Novo Nordic Foundation, Assistance Publique - Hôpitaux de Paris, Direction Générale de l'Offre de Soins

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
ALLTogether collects the experience of previously successful treatment of infants, children and young adults, with ALL from a number of well-renowned study groups into a new master protocol, which is both a comprehensive system for stratification and treatment of ALL in this age-group as well as the basis for several randomised and interventional trials included in the study-design.
Detailed Description
ALLTogether is a European clinical treatment study for acute lymphoblastic leukaemia (ALL) in infants, children and young adults. The aims are to improve survival and quality of survival. In young people, ALL has excellent outcome with an overall survival of about 92% in children and 75% in young adults. Infants with BCP-ALL and KMT2A-rearrangements have a worse outcome and are treated according to separate protocols, but infants with KMT2A-germline and T-cell ALL have acceptable outcome on standard ALL therapy. However, patients still die of disease - from relapse because of under-treatment and a large fraction of patients are also over-treated: All patients risk treatment-related death and some suffer long-term side-effects or secondary cancer. To show improvement with such good survival, large populations are needed. Study groups from Sweden, Norway, Iceland, Denmark, Finland, Estonia and Lithuania (NOPHO), the UK (UKALL), the Netherlands (DCOG), Germany (COALL), Belgium (BSPHO), Portugal (SHOP), Ireland (PHOAI), and France (SFCE), have designed a common treatment protocol. The study has a complex clinical trial design with sub-protocols (the randomisations / intervention) connected to a master protocol. The master protocol consists of well established therapy-elements and in its design typical for current ALL therapy. The master protocol therapy is in the study design considered as standard of care (SOC) therapy for infants, children and young adults with ALL. The study structure is defined by a master protocol onto which randomised and interventional sub-protocols as well as sub-studies may be added, run and stop in a modular fashion. The randomisations / intervention may identify therapy that is less toxic, but equally efficacious for sub-groups of patients and innovative therapy that may reduce relapses and death from ALL. In the master protocol, improved risk-stratification is likely to increase survival and reduce unnecessary toxicity and the introduction of therapeutic drug monitoring (TDM) of Asparaginase activity will make the use of Asparaginase more rational and efficient and may thus improve overall outcomes. The investigators hypothesise that patients stratified to the standard-risk group are over-treated. Therefore, it will be tested if the treatment can be safely reduced. In the R1 randomisation, patients will be randomised to receiving the Delayed Intensification (DI) phase of therapy with or without the anthracycline Doxorubicin. A similar hypothesis of over-treatment will also be tested in patients stratified to the intermediate risk-low group. In the R2 randomisation patients will be randomly assigned to either removal of Doxorubicin during the DI phase or removal of Vincristine and Dexamethasone pulses during the maintenance phase or to the control group, which will be treated with Doxorubicin in DI as well as Vincristine and Dexamethasone pulses during maintenance. Patients will only be randomised once. Randomisation R1 and R2 are only considered for children since adults have worse outcome and very poor survival after relapse, but the risk-stratification is likely to reduce the number of high-risk cases also in the adult-group. Patients stratified as intermediate risk-high (IR-high) are identified as having an increased risk of relapse and thus a less favourable prognosis than the standard- and intermediate risk-low groups, but a more favourable prognosis than the high risk patients. The majority of all relapses in childhood ALL is expected to occur in the IR-high group. Following a relapse, only approximately 40% of the children can be successfully treated again and for adults the corresponding figure is less than 20 %, so preventing relapses is very important. New treatment options that improves the antileukaemic efficacy and which have an improved safety profile are urgently needed. For IR-high patients Randomisation 3 (R3) is available. In R3 patients will be randomised to receive either: the addition of two cycles of Inotuzumab ozogamicin (InO) - Besponsa®, before start of the maintenance phase. After these cycles, the patients randomised to the InO arm will receive maintenance for the same duration as in the control arm. the addition of low dose 6-tioguanine (6TG) as an addition to the standard maintenance therapy. standard maintenance therapy Patients with ABL-class fusions in their leukaemic clone will, as a non-randomised experimental intervention, be treated with an addition of a tyrosine-kinase inhibitor during the induction phase (for patients <25 years) and from the consolidation phase (patients ≥25 years). This intervention may shift therapy for previously resistant cases to lower intensity treatment with the associated reduced morbidity and may also reduce the number of relapses in analogy with the results in Ph+ ALL. The reason for not performing a randomised comparison is the rarity of the aberration and also the diversity of ABL-class fusions, reducing statistical power for any comparison further. For this reason, the results of this intervention may be pooled with other study-groups trying similar approaches. A new intervention is introduced for Down syndrome patients with CD19 positive ALL: ALLTogether1 DS (NRI2). For Down syndrome-ALL patients who have end of Induction MRD detectable but <25% two conventional chemotherapy consolidation blocks will be replaced with two blocks of Blinatumomab. For high-risk B-lineage patients, CAR-T therapy can be an alternative to high-risk blocks and stem-cell transplant, but in this case the intervention (CAR-T infusion) will be performed outside the ALLTogether1 study. However, the stratification-system in ALLTogether1 will define the population with a potential CAR-T indication. ALLTogether1 also includes five sub-studies: Efficacy and pharmacokinetics of Imatinib in ABL-class fusion positive ALL Target population: All ABL-class patients enrolled in the ALLTogether study. Biomaterials to be collected at diagnosis, during TKI treatment, follow-up and relapse. Aims To determine the efficacy and dosing target of imatinib in the treatment of ABL-class leukemia To find the best discriminative biomarkers for TKI response in ABL-class ALL To determine the frequency of intrinsic (at diagnosis) and acquired TKI resistance (due to treatment), including backtracking of mutations using imatinib PK/PD findings during treatment To find causes of TKI resistance in ABL-class patients To describe the pharmacokinetics of Imatinib in TKI-treated patients Objectives To determine the percent of ABL-class patients who need to switch from IR-high to HR because of high MRD levels To determine the effect of imatinib exposure on clinical outcome, including pharmacokinetic measurements of imatinib To determine the molecular response to imatinib by monitoring fusion gene levels and mutational spectrum at diagnosis and during follow up To determine whether the molecular response parameters reflect the Ig/TCR MRD or flow-MRD response or are a better predictor of therapy failure than Ig/TCR or flow-based MRD monitoring To determine the phosphorylation status of ABL-class proteins and presence of TKI-resistance associated mutations in ABL genes prior to imatinib treatment and the emergence of such mutations during treatment with imatinib To determine the presence of mutations in regulatory /other genes before and during imatinib treatment and functionally address the importance of these mutations in TKI resistance To determine whether the efficacy of TKIs depends on the type of fusion gene To describe inter- and intraindividual variations in imatinib PK (=trough levels) during therapy of ABL-class ALL To describe associations between PK of imatinib and end-of-induction MRD (<25 yrs only) and end-of-consolidation MRD (all patients) To describe associations between imatinib PK and relapse rates (overall, bone-marrow and CNS), event-free survival as well as overall survival; To describe associations between imatinib PK and toxicities (including e.g. height z-scores at diagnosis and end of therapy, pancreatitis, treatment delays) with focus on those toxicities that are routinely monitored in ALLTogether. Biomarkers to Reform Approaches to therapy-Induced Neurotoxicity (BRAIN) Target population: All patients registered on ALLTogether1 aged ≥ 4 years at end of therapy (Arm A) and all patients registered on ALLTogether1 aged 4-21 years at start of therapy (Arm B) and without: Pre-existing neurodevelopmental delay (e.g Trisomy 21) prior to diagnosis of ALL Significant visual or motor impairment preventing use of a touch screen ipad All centres are invited to enrol to arm A (Main BRAIN) of the study. Arm B (Longitudinal BRAIN) will be carried out in selected centres. Aims To implement universal screening of all children for adverse neurocognitive outcomes at the end of treatment using a validated user-friendly computer software programme (CogState) and compare neurocognitive outcomes by treatment allocation (Arm A). To identify risk factors for adverse outcomes including whether acute neurotoxic events are associated with poor performance on cognitive tests at end of therapy compared to patients without acute neurotoxicity (Arm A). To examine changes in neurocognitive performance over time and the risk/protective factors associated with differences in outcome, such as demographic, clinical, and physical/psychosocial factors (Arm B). Primary end-point a. Proportion of children with a z-score <1.5 on detection and/or identification CogState tasks in each treatment arm at the end of ALL therapy. A z-score < 1.5 correlates with moderate cognitive impairment at a level that may require additional support. Secondary and exploratory end-points Association between CogState scores at end of treatment and overt neurotoxic episodes as recorded on the trial adverse event database. Association between Cogstate scores and clinical and demographic variables - age, sex, ethnicity, CNS status. Proportion of children with scores <1.5SD for one card learning (learning), one back (working memory) and Groton's maze (executive function) on different treatment arms. Association between CogState scores and patient reported outcome measures/Quality of life measurements collected as part of the main ALLTogether1 trial. Changes in neurocognitive scores over time, including CogState and BRIEF-2/BRIEF-A scores. Association between neurocognitive scores over time and interactions with demographic variables (age, sex), clinical variables (treatment arm, neurotoxicity), social-emotional and physical functioning (SDQ, PedsQL 4.0 Generic; PedsQL 3.0 Fatigue), and family factors (MEES; PedsQL FIM) Association between asparaginase activity levels and outcome Target population: All patients included in the ALLTogether1 protocol are eligible for participation. Primary aim To study the association between asparaginase activity levels and outcome (MRD, relapse, survival) Secondary aims To evaluate the association between asparaginase activity levels and toxicities, such as pancreatitis, infections and deep venous thrombosis (DVT) To evaluate the association between asparaginase activity levels and hepatotoxicity in a subset of patients CSF-Flow Target population: All patients included in the ALLTogether1 protocol are eligible for participation Aims To use cerebrospinal fluid (CSF) flow cytometry (FCM) to improve the accuracy of diagnostic tests for CNS leukaemia compared to conventional CSF cytology. An associated objective will be to develop a recommended protocol for CSF flow cytometry with external quality assessment to ensure uniformity of measurement across the ALLTogether consortium. To investigate whether negative FCM identifies a group of children at very low risk of CNS relapse, suitable for testing de-escalation of CNS-directed therapy in future trials. To investigate whether positive FCM can identify children at increased risk of CNS relapse and whether patients with persistent positivity (FCM positive at day 15 onwards) might benefit from studies testing escalated CNS-directed therapy or a switch to more intensive treatment arms. To collect matching CSF supernatant for studies comparing CSF FCM with soluble biomarkers (e.g. metabolic, cell-free DNA, proteomic and microRNA). Maintenance therapy pharmacokinetics/-dynamics study Target population: All patients included in the ALLTogether1 protocol are eligible for participation. For IR-high patients participating in the randomised InO- and TEAM sub-protocols, the monitoring of 6-mercaptopurine (6MP)/Methotrexate (MTX) metabolites at three months intervals is mandatory. Aims and specific objectives To map pharmacokinetics of 6MP and MTX during maintenance therapy in all patients in the ALLTogether protocol. To associate metabolite profiles with TPMT and NUDT15 variants, as routinely analysed in ALLTogether. To explore the association of event-free survival with DNA-TG and other 6MP/MTX metabolites. To explore the association between risk of second cancers with DNA-TG and other 6MP/MTX metabolites. To explore the association of risk of invasive infections with DNA-TG and other 6MP/MTX metabolites. To explore the association of risk of osteonecrosis with DNA-TG and other 6MP/MTX metabolites. To explore the association of sinusoidal obstruction syndrome with DNA-TG and other 6MP/MTX metabolites.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Acute Lymphoblastic
Keywords
Leukemia, Acute Leukemia, ALL, ALLTogether, Leukaemia, Inotuzumab ozogamicin, Besponsa, ALLTogether1, Blinatumomab, Blincyto, 6-tioguanine, 6-thioguanine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Sequential Assignment
Model Description
Master protocol with risk-stratification. The risk-stratified groups will proceed to non-randomised or randomised interventions in single arm (TKI) and (Blinatumomab) and parallel (R1/R2/R3) models respectively.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
6430 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
R1 - SR standard arm
Arm Type
No Intervention
Arm Description
Standard risk arm receiving standard treatment (Delayed Intensification including Doxorubicin).
Arm Title
R1 - SR experimental arm
Arm Type
Experimental
Arm Description
Standard risk arm, receiving Delayed Intensification without Doxorubicin IV 3 x 30 mg/m2/dose.
Arm Title
R2 - IR-low standard arm
Arm Type
No Intervention
Arm Description
Standard treatment with Delayed Intensification including Doxorubicin and Maintenance including Vincristine+Dexamethasone pulses.
Arm Title
R2 - IR-low experimental arm A
Arm Type
Experimental
Arm Description
Standard treatment with omission of Doxorubicin IV 3 x 30 mg/m2/dose in the Delayed Intensification phase.
Arm Title
R3 - IR-high standard arm
Arm Type
No Intervention
Arm Description
Intermediate risk high arm receiving Standard Maintenance Therapy.
Arm Title
R3-InO - IR-high experimental arm
Arm Type
Experimental
Arm Description
Inotuzumab IV 0,5 mg/m2, given on days 253, 260, 267 and on days 274, 281, 288 before start of Standard Maintenance Therapy.
Arm Title
ABL-class fusions intervention
Arm Type
Experimental
Arm Description
Imatinib p.o. 340 mg/m2 given daily from day 15 or 30 (depending on age) to the end of therapy (week 106) in addition to Standard IR-high chemotherapy.
Arm Title
R3-TEAM - IR-high experimental arm
Arm Type
Experimental
Arm Description
6-tioguanine p.o, 2,5-12,5 mg/m2, given daily in addition to Standard Maintenance Therapy.
Arm Title
ALLTogether1 DS Blinatumomab intervention
Arm Type
Experimental
Arm Description
Blinatumomab IV, 5 mcg/m2/day up to 28 mcg/day (detailed dosing in protocol) continous infusion. Two 28 day courses with a two week treatment free interval in between. Blinatumomab courses replace Consolidation 1 and Consolidation 2 in the standard protocol adapted for Down syndrome patients.
Arm Title
R2 - IR-low experimental arm B
Arm Type
Experimental
Arm Description
Standard treatment with omission of monthly pulses of Vincristine IV 1,5 mg/m2/dose and 5 days of Dexamethasone p.o. 6 mg/m2/day in the Maintenance Phase.
Intervention Type
Drug
Intervention Name(s)
Omitted Doxorubicin
Intervention Description
Omission of IV Doxorubicin
Intervention Type
Drug
Intervention Name(s)
Omitted Vincristine+Dexamethasone pulses
Intervention Description
Omission of Vincristine+Dexamethasone pulses
Intervention Type
Drug
Intervention Name(s)
Inotuzumab Ozogamicin+Standard Maintenance Therapy
Other Intervention Name(s)
Besponsa+Maintenance Therapy
Intervention Description
Addition of IV Inotuzumab ozogamicin before Maintenance Therapy
Intervention Type
Drug
Intervention Name(s)
Imatinib
Intervention Description
p.o. Imatinib
Intervention Type
Drug
Intervention Name(s)
6-tioguanine+Standard Maintenance Therapy
Intervention Description
Addition of p.o. 6-tioguanine to Standard Maintenance Therapy
Intervention Type
Drug
Intervention Name(s)
Blinatumomab
Other Intervention Name(s)
Blincyto
Intervention Description
IV Blinatumomab
Primary Outcome Measure Information:
Title
Event-free survival (EFS) for the whole protocol
Description
The primary endpoint for the whole protocol (compared with the legacy protocols of the participating study-groups forming the consortium) is event-free survival (EFS) - as defined in the protocol.
Time Frame
5 year estimates from the time of diagnosis will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up.
Title
Event-free survival (EFS) for the TKI intervention
Description
The primary endpoint for the TKI intervention is event-free survival (EFS) - as defined in the protocol, from the start of TKI until event or end of follow-up
Time Frame
From the start of TKI (day 15 or day 30), 5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up for all interventions except Inotuzumab-randomisation (minimum 2-year follow-up).
Title
Disease-free survival (DFS) R1 + R2
Description
The primary endpoint for Randomisation 1 and 2 is disease-free survival (DFS) - as defined in the protocol counting from the time of randomisation
Time Frame
5 and 8 year estimates from the time of randomisation will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up.
Title
Disease-free survival (DFS) R3
Description
The primary endpoint for Randomisation 3 and the ABL-class fusion intervention is disease-free survival (DFS) - as defined in the protocol counting from the time of randomisation (R3) and the start of TKI-therapy (ABL-class fusion intervention).
Time Frame
5 year estimates from the time of randomisation will be measured but adequate follow-up for these estimates will be ensured: at least 2-year follow-up
Title
MRD response after 1 cycle of Blinatumomab
Description
Fraction of patients with undetectable MRD ("Complete MRD response") at the end of one cycle of Blinatumomab (+/- 1 week)
Time Frame
End of first Blinatumomab infusion +/- 1 week
Secondary Outcome Measure Information:
Title
Overall survival (OS) for the whole protocol
Description
Overall survival defined as time from diagnosis to death or end of follow-up for surviving patients.
Time Frame
5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up.
Title
Overall survival (OS) for R1 + R2
Description
Overall survival defined as time from randomisation to death or end of follow-up for surviving patients.
Time Frame
5 and 8 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up.
Title
Overall survival (OS) for R3
Description
Overall survival defined as time from randomisation to death or end of follow-up for surviving patients.
Time Frame
5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 2 years follow-up
Title
Overall survival (OS) for R3-TEAM associated with DNA-TG
Description
Overall survival as defined above in relation to DNA-TG.
Time Frame
5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 2 years follow-up
Title
Overall survival (OS) for TKI
Description
Overall survival defined as time from start of TKI to death or end of follow-up for surviving patients
Time Frame
5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up (TKI).
Title
Overall survival (OS) for ALLTogether1 DS
Description
Overall survival defined as time from start of Blinatumomab to death or end of follow-up for surviving patients
Time Frame
5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up.
Title
Induction death
Description
Fraction of patients who die as well as cumulative incidence of death before achieved complete remission (CR) within the time-frame described in the protocol
Time Frame
From diagnosis until death before remission (at the earliest, day 29) or in case of no CR day 29, completion of induction and consolidation 1 (protocol day 99 - Down) and in addition 3 high-risk blocks (protocol day 134 - all other patients)
Title
Resistant disease
Description
Fraction of patients as well as cumulative incidence of resistant disease as described in the protocol. Induction death as competing risk.
Time Frame
From diagnosis until achieved complete remission (at the earliest, day 29) or in case of no CR day 29, assessment after induction and consolidation 1 (protocol day 99-Down patients) and in addition 3 high-risk blocks (protocol day 134-all other patients)
Title
Cumulative incidence of relapse for the whole protocol
Description
Time from achieved complete remission until relapse as defined in the protocol or end of follow-up. Second malignancy, death in complete remission as competing events.
Time Frame
5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up.
Title
Cumulative incidence of relapse for R1 + R2
Description
Time from randomisation until relapse as defined in the protocol or end of follow-up. Second malignancy, death in complete remission as competing events.
Time Frame
5 and 8 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up.
Title
Cumulative incidence relapse for R3
Description
Time from randomisation until relapse as defined in the protocol or end of follow-up. Second malignancy, death in complete remission as competing events.
Time Frame
5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 2 years follow-up
Title
Cumulative incidence relapse for R3-TEAM in association with DNA-TG
Description
Cumulative incidence of relapse as defined for R3 in association with DNA-TG for R3-TEAM. Second malignancy, death in complete remission as competing events.
Time Frame
5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 2 years follow-up
Title
Cumulative incidence CD22 negative relapse for R3
Description
Time from randomisation until relapse without expression of CD22 as defined in the protocol or end of follow-up. Second malignancy, death in complete remission and relapse with CD22 expression as competing events.
Time Frame
5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 2 years follow-up
Title
Cumulative incidence relapse for TKI
Description
Time from start of TKI until relapse as defined in the protocol or end of follow-up. Second malignancy, death in complete remission as competing events.
Time Frame
5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up
Title
Cumulative incidence relapse for ALLTogether1 DS
Description
Time from start of Blinatumomab until relapse as defined in the protocol or end of follow-up. Second malignancy, death in complete remission as competing events.
Time Frame
5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up
Title
Cumulative incidence of CD19 negative relapse for ALLTogether1 DS
Description
Time from start of Blinatumomab until CD19 negative relapse as defined in the protocol or end of follow-up. Second malignancy, death in complete remission and CD19 positive relapse as competing events.
Time Frame
5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up
Title
Cumulative incidence of second malignant neoplasm (SMN) for the whole protocol
Description
Time from achieved complete remission until diagnosis of second malignant neoplasm as defined in the protocol or end of follow-up. Relapse and death in complete remission as competing events.
Time Frame
5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up.
Title
Cumulative incidence of second malignancy for R1+R2
Description
Time from randomisation until diagnosis of second malignant neoplasm as defined in the protocol or end of follow-up. Relapse and death in complete remission as competing events.
Time Frame
5 and 8 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up.
Title
Cumulative incidence of second malignancy for R3
Description
Time from randomisation until diagnosis of second malignant neoplasm as defined in the protocol or end of follow-up. Relapse and death in complete remission as competing events.
Time Frame
5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 2 years follow-up.
Title
Cumulative incidence of second malignancy for R3-TEAM in association with DNA-TG
Description
Cumulative incidence of second malignancy as defined above for R3 in association with DNA-TG for R3-TEAM. Relapse and death in complete remission as competing events.
Time Frame
5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 2 years follow-up.
Title
Cumulative incidence of second malignancy for TKI
Description
Time from start of TKI until diagnosis of second malignant neoplasm as defined in the protocol or end of follow-up. Relapse and death in complete remission as competing events.
Time Frame
5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up.
Title
Cumulative incidence of second malignancy for ALLTogether1 DS
Description
Time from start of Blinatumomab until diagnosis of second malignant neoplasm as defined in the protocol or end of follow-up. Relapse and death in complete remission as competing events.
Time Frame
5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up.
Title
Cumulative incidence of death in complete remission for the whole protocol
Description
Time from achieved complete remission until death in complete remission as defined in the protocol or end of follow-up. Relapse and second malignant neoplasm as competing events.
Time Frame
5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up.
Title
Cumulative incidence of death in complete remission for R1+R2
Description
Time from randomisation until death in complete remission as defined in the protocol or end of follow-up. Relapse and second malignant neoplasm as competing events.
Time Frame
5 and 8 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 2 years follow-up.
Title
Cumulative incidence of death in complete remission for R3
Description
Time from randomisation until death in complete remission as defined in the protocol or end of follow-up. Relapse and second malignant neoplasm as competing events.
Time Frame
5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 2 years follow-up
Title
Cumulative incidence of death in complete remission for TKI
Description
Time from start of TKI until death in complete remission as defined in the protocol or end of follow-up. Relapse and second malignant neoplasm as competing events.
Time Frame
5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up
Title
Cumulative incidence of death in complete remission for ALLTogether1 DS
Description
Time from start of Blinatumomab until death in complete remission as defined in the protocol or end of follow-up. Relapse and second malignant neoplasm as competing events.
Time Frame
5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up
Title
Cumulative incidence of treatment-related mortality for the whole protocol
Description
Time from diagnosis until death during induction, death in complete remission or death from second malignant neoplasm (if not related to SMN-treatment).
Time Frame
5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up.
Title
Cumulative incidence of treatment-related mortality R1+R2
Description
Time from randomisation until death in complete remission or death from second malignant neoplasm (if not related to SMN-treatment).
Time Frame
5 and 8 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 2 years follow-up.
Title
Cumulative incidence of treatment-related mortality R3
Description
Time from randomisation until death in complete remission or death from second malignant neoplasm (if not related to SMN-treatment).
Time Frame
5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 2 years follow-up
Title
Cumulative incidence of treatment-related mortality TKI
Description
Time from start of TKI until death in complete remission or death from second malignant neoplasm (if not related to SMN-treatment).
Time Frame
5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up
Title
Leukaemia specific mortality for the whole protocol
Description
Time from diagnosis until death after resistant disease or relapse - as defined in the protocol.
Time Frame
5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up.
Title
Leukaemia specific mortality for R1+R2
Description
Time from randomisation until death after relapse - as defined in the protocol.
Time Frame
5 and 8 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up.
Title
Leukaemia specific mortality for R3
Description
Time from randomisation until death after relapse - as defined in the protocol.
Time Frame
5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 2 years follow-up
Title
Leukaemia specific mortality for TKI
Description
Time from start of TKI until death after relapse - as defined in the protocol.
Time Frame
5 year estimates will be measured but adequate follow-up for these estimates will be ensured: at least 5 years follow-up
Title
Incidence of Adverse Events of Special Interest (AESIs) per treatment-phase in the whole protocol and TKI intervention
Description
Cumulative incidence of 19 AESIs as defined in the protocol
Time Frame
From time of diagnosis after each treatment-phase (one extra in the middle of maintenance) and annually until 5 years from discontinuation of therapy.
Title
Incidence of Adverse Events of Special Interest (AESIs) extra assessment (R1+R2)
Description
Cumulative incidence of 4 additional AESIs as defined in the protocol
Time Frame
Cumulative incidence of AESIs estimated 3 months after start of maintenance (R1+R2) and at the end of maintenance (R2)
Title
Incidence of Adverse Events of Special Interest (AESIs) extra assessment (R3)
Description
Cumulative incidence of 3 additional AESIs as defined in the protocol
Time Frame
Cumulative incidence of AESIs estimated at the end of maintenance.
Title
Incidence of Serious Adverse Events (SAEs) and Adverse Events (AEs) related to R3
Description
Cumulative incidence of SAEs and AEs (with limitations) as defined in the protocol
Time Frame
From time of randomisation until the end of maintenance therapy (approximately 77 weeks from randomisation)
Title
Quantitative measures of toxicity R1+R2
Description
Days: in hospital, with iv antibiotics, with iv analgesics, with iv nutritional support
Time Frame
From time of randomisation, assessment after delayed intensification and 6 weeks after start of maintenance
Title
Metabolic consequences of steroid exposure (R2)
Description
Measurements of BMI
Time Frame
At the end of therapy (approximately 94 weeks from randomisation) and 5 years after discontinuation of treatment
Title
Association of Disease-free survival (DFS) with DNA-TG for R3-TEAM
Description
Disease-free survival (DFS) - as defined above associated with DNA-TG.
Time Frame
5 year estimates from the time of randomisation will be measured but adequate follow-up for these estimates will be ensured: at least 2-year follow-up
Title
Cumulative incidence of Sinusoidal Obstruction Syndrome (SOS) and Nodular Regenerative Hyperplasia (NRH) for R3-TEAM
Description
Time from randomisation until diagnosis of SOS or NRH as defined in the protocol or end of follow-up.
Time Frame
Cumulative incidence of SOS/NRH estimated at the end of follow-up.
Title
Cumulative incidence of Osteonecrosis for R3-TEAM
Description
Time from randomisation until diagnosis of osteonecrosis as defined in the protocol or end of follow-up.
Time Frame
Cumulative incidence of osteonecrosis estimated at the end of follow-up.
Title
Event-free survival (EFS) for ALLTogether1 DS
Description
Event-free survival as defined in the protocol, from the start of Blinatumomab until death from any cause, relapse, second malignancy, protocol therapy failure (MRD>1% after 2 cycles blinatumomab and Augmented BFM consolidation) or end of follow-up.
Time Frame
From the start of Blinatumomab, 5 year estimate will be measured but adequate follow-up for this estimate will be ensured: at least 5 years follow-up.
Title
Incidence of Blinatumomab refractory disease for ALLTogether1 DS
Description
Incidence of progressive disease under Blinatumomab treatment or MRD ≥1% at the end of the 2nd cycle of Blinatumomab.
Time Frame
From the start of Blinatumomab until end of 2nd cycle of Blinatumomab (each cycle is 4 weeks followed by a 2-week treatment free period)
Title
Incidence of Protocol Therapy Failure for ALLTogether1 DS
Description
Incidence of patients who have MRD ≥1 % post 2 cycles of Blinatumomab followed by Augmented BFM consolidation, corresponding to original protocol day 99, or unchanged/increasing MRD during Augmented BFM consolidation corresponding to original protocol day 57.
Time Frame
From the start of Blinatumomab until the end of Consolidation 1 (85-140 days: 15-70 days of Blinatumomab therapy + 70 days of Consolidation 1)
Other Pre-specified Outcome Measures:
Title
6-mercaptopurine and Methotrexate metabolite pharmacokinetics (i.e. Ery-TGN/MeMP/MTXpg) for R3-TEAM
Description
Measurements of metabolites Ery-TGN/MeMP/MTXpg during Maintenance therapy.
Time Frame
From start of Maintenance therapy until the end of Maintenance therapy (protocol week 38 until protocol week 108)
Title
Abnormal liver function parameters (including hypoglycemia) for R3-TEAM
Description
Liver function parameters including hypoglycemia during Maintenance therapy
Time Frame
From start of Maintenance therapy until the end of Maintenance therapy (protocol week 38 until protocol week 108)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
0 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients newly diagnosed with T-lymphoblastic (T-cell) or B-lymphoblastic precursor (BCP) leukaemia (ALL) according to the WHO-classification of Tumours of Haematopoetic and Lymphoid Tissues (Revised 4th edition 2017) and with a diagnosis confirmed by an accredited laboratory at a participating paediatric oncology or adult haematology centre. Age 0 - < 46 years (one day before 46th birthday) at the time of diagnosis with the exception of infants with KMT2A-rearranged (KMT2A-r) BCP ALL. Patients with surface immunoglobulin negative (sIG-) BCP-ALL and an IG::MYC rearrangement, unless they have a concurrent BCL2/6 rearrangement. T-ALL patients with MYC translocations. Informed consent signed by the patient and/or parents/legal guardians according to country-specific age-related guidelines. The ALL diagnosis should be confirmed by an accredited laboratory at a participating paediatric oncology or adult haematology centre. The patient should be diagnosed and treated at a participating paediatric oncology or adult haematology centre in the participating countries. The patient should be a resident in one of the participating countries on a permanent basis or should intend to settle in a participating country, for instance by an application for asylum. Patients who are visiting the country as tourists should not be included. However, returning expatriots with primary diagnosis abroad may be included if no treatment has been administered and the diagnostic procedures are repeated at a participating centre. All women of childbearing potential (WOCBP) have to have a negative pregnancy test within 2 weeks prior to the start of treatment. For each intervention/randomisation an additional set of inclusion-criteria is provided. Exclusion Criteria: Age < 365 days and KMT2A-rearranged (KMT2A-r) BCP-ALL (documented presence of a KMT2A-split by FISH and/or a KMT2A fusion transcript). Age >45 years at diagnosis. Patients with a previous malignant diagnosis (ALL as a second malignant neoplasm - SMN). Relapse of ALL. Patients with mature B-ALL (as defined by surface IG positivity) or any patients with IG::MYC and a concurrent BCL2/6 rearrangement. Patients with Ph-positive ALL (documented presence of t(9;22)(q34;q11) and/or of the BCR::ABL fusion transcript). These patients will be transferred to an appropriate trial for t(9;22) if available. Previously known ALL prone syndromes (e.g. Li-Fraumeni syndrome, germline ETV6 mutation), except for Down syndrome. Exploration for such ALL prone syndromes is not mandatory and patients in whom genetic work-up reveals a new germ-line mutation (index-cases) will remain in the study. Treatment with systemic corticosteroids (>10mg/m2/day) for more than one week and/or other chemotherapeutic agents in a 4-week interval prior to diagnosis (pre-treatment). Pre-existing contraindications to any treatment according to the ALLTogether protocol (constitutional or acquired disease prior to the diagnosis of ALL preventing adequate treatment). Any other disease or condition, as determined by the investigator, which could interfere with the participation in the study according to the study protocol, or with the ability of the patients to cooperate and comply with the study procedures. Women of childbearing potential who are pregnant at the time of diagnosis. Women of childbearing potential and fertile men who are sexually active and are unwilling to use adequate contraception during therapy. Efficient birth control is required. Female patients, who are breast-feeding. Essential data missing from the registration of characteristics at diagnosis (in consultation with the protocol chair). For each intervention/randomisation an additional set of exclusion-criteria is provided.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Global Clinical Trial Manager ALLTogether1
Phone
+46 8 524 800 00
Email
karin.flood@ki.se
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mats Heyman, MD, PhD
Organizational Affiliation
Karolinska University Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
L'hôpital Universitaire des enfants Reine Fabiola (Huderf)
City
Brussels
ZIP/Postal Code
1020
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Laurence Dedeken, M.D.
Facility Name
Cliniques Universitaires Saint-Luc (UCL)
City
Brussels
ZIP/Postal Code
1200
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maelle Deville, M.D.
Facility Name
University Hospital Antwerp
City
Edegem
ZIP/Postal Code
2650
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Koen Norga, M.D.
Facility Name
University Hospital Ghent
City
Ghent
ZIP/Postal Code
9000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Veerle Mondelaers, M.D.
Facility Name
University Hospital Leuven, Dept of Paediatrics
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Heidi Segers, M.D.
Facility Name
CHC MontLégia, Boulevard Patience et Beaujonc 2
City
Liège
ZIP/Postal Code
4000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christophe Chantrain, M.D.
Facility Name
CHR de la Citadelle
City
Liège
ZIP/Postal Code
4000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marie-Françoise Dresse, M.D.
Facility Name
Aalborg University Hospital, Dept of Paediatrics
City
Aalborg
ZIP/Postal Code
9000
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ruta Tuckuviene, M.D.
Facility Name
Aarhus University Hospital
City
Aarhus
ZIP/Postal Code
8000
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ingolf Mølle, M.D.
Facility Name
Aarhus University Hospital, Child and Adolescent Health
City
Aarhus
ZIP/Postal Code
8200
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Birgitte Klug Albertsen, M.D.
Facility Name
Rigshospitalet, Dept of Haematology
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ulrik Malthe Overgaard, M.D.
Facility Name
Rigshospitalet, Dept of Paediatrics
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bodil Als-Nielsen, M.D.
Facility Name
Odense University Hospital, Dept of Paediatrics
City
Odense
ZIP/Postal Code
5000
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peder Skov Wehner, M.D.
Facility Name
North Estonia Medical Centre, Dept of Haematology
City
Tallinn
ZIP/Postal Code
13419
Country
Estonia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Katrin Palk, M.D.
Facility Name
Tallinn Children´s Hospital, Dept of Paediatrics
City
Tallinn
ZIP/Postal Code
13419
Country
Estonia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kristi Lepik, M.D.
Facility Name
Tartu University Hospital
City
Tartu
ZIP/Postal Code
50406
Country
Estonia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mari Punab, M.D.
Facility Name
Helsinki University Hospital, Dept of Haematology
City
Helsinki
ZIP/Postal Code
00029
Country
Finland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ulla Wartiovaara-Kautto, M.D.
Facility Name
Helsinki University Hospital, Dept of Paediatrics
City
Helsinki
ZIP/Postal Code
00029
Country
Finland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antti Kyrönlahti, M.D.
Facility Name
Kuopio University Hospital, Dept of Haematology
City
Kuopio
ZIP/Postal Code
70029
Country
Finland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marja Pyörälä, M.D.
Facility Name
Kuopio University Hospital, Dept of Paediatrics
City
Kuopio
ZIP/Postal Code
70029
Country
Finland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kaisa Vepsäläinen, M.D.
Facility Name
Oulu University Hospital, Dept of Haematology, Dept of Medicine
City
Oulu
ZIP/Postal Code
90029
Country
Finland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Timo Siitonen, M.D.
Facility Name
Oulu University Hospital, Dept of Paediatrics
City
Oulu
ZIP/Postal Code
90029
Country
Finland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Riitta Niinimäki, M.D.
Facility Name
Tampere University Hospital, Dept of Haematology
City
Tampere
ZIP/Postal Code
33521
Country
Finland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Johanna Rimpiläinen, M.D.
Facility Name
Tampere University Hospital, Dept of Paediatrics
City
Tampere
ZIP/Postal Code
33521
Country
Finland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Olli Lohi, M.D.
Facility Name
Turku University Hospital, Clinical Haematology and Stem Cell Transplantation Unit
City
Turku
ZIP/Postal Code
20520
Country
Finland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pia Ettala, M.D.
Facility Name
Turku University Hospital, Dept of Paediatrics
City
Turku
ZIP/Postal Code
20520
Country
Finland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Päivi Lähteenmäki, M.D.
Facility Name
CHU Amiens Groupe Hospitalier Sud
City
Amiens Cedex 1
ZIP/Postal Code
80054
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Camille Leglise, M.D.
Facility Name
CHU Angers
City
Angers Cedex 9
ZIP/Postal Code
49033
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mylène Duplan, M.D.
Facility Name
CHRU Besançon
City
Besancon Cedex 03
ZIP/Postal Code
25030
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pauline Simon, M.D.
Facility Name
CHU Bordeaux - Groupe Hospitalier Pellegrin
City
Bordeaux Cedex
ZIP/Postal Code
33076
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stéphane Ducassou, M.D.
Facility Name
CHRU Brest - Morvan
City
Brest Cedex
ZIP/Postal Code
29609
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Liana Carausu, M.D.
Facility Name
Centre Hospitalier Universitaire Caen
City
Caen Cedex 9
ZIP/Postal Code
14033
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Damien Bodet, M.D.
Facility Name
CHU Clermont-Ferrand
City
Clermont-ferrand
ZIP/Postal Code
63000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Justyna Kanold, M.D.
Facility Name
CHU Dijon Hôpital François Mitterrand
City
Dijon
ZIP/Postal Code
21000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Claire Desplantes, M.D.
Facility Name
CHU de Grenoble site Nord - Hôpital Albert Michallon
City
Grenoble Cedex 9
ZIP/Postal Code
38043
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Corine Armari Alla
Facility Name
CHRU de Lille - Hôpital Jeanne de Flandre
City
Lille Cedex
ZIP/Postal Code
59037
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wadih Abou Chahla, M.D.
Facility Name
Hôpital de la mère et de l'enfant
City
Limoges
ZIP/Postal Code
87042
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christophe Piguet, M.D.
Facility Name
CHU de Lyon HCL - GH Est-Institut d'hématologie et d'oncologie pédiatrique IHOP
City
Lyon Cedex 08
ZIP/Postal Code
69373
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carine Halfon-Domenech, M.D.
Facility Name
CHU de Marseille - Hôpital de la Timone
City
Marseille Cedex 5
ZIP/Postal Code
13385
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Paul Saultier, M.D.
Facility Name
CHU de Montpellier - Hôpital Arnaud de Villeneuve
City
Montpellier Cedex 5
ZIP/Postal Code
34295
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stéphanie Haouy, M.D.
Facility Name
CHU Nantes-Hôpital enfant-adolescent
City
Nantes Cedex 01
ZIP/Postal Code
44093
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Caroline Thomas, M.D.
Facility Name
CHU Nice - Hôpital l'Archet 2
City
Nice
ZIP/Postal Code
6200
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pierre-Simon Rohrlich, M.D.
Facility Name
CHU Paris Saint Louis
City
Paris
ZIP/Postal Code
75010
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nicolas Boissel, M.D.
Facility Name
CHU Paris Armand Trousseau
City
Paris
ZIP/Postal Code
75012
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Arnaud Petit, M.D.
Facility Name
CHU Paris - Hôpital Robert Debré
City
Paris
ZIP/Postal Code
75019
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marion Strullu, M.D.
Facility Name
CHU Poitiers
City
Poitiers Cedex 6
ZIP/Postal Code
86021
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Frédéric Millot
Facility Name
CHU Reims-American Hospital
City
Reims
ZIP/Postal Code
51100
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Claire Pluchart, M.D.
Facility Name
CHU Rennes - Hôpital sud
City
Rennes Cedex 2
ZIP/Postal Code
35203
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Virginie Gandemer, M.D.
Facility Name
CHU Rouen
City
Rouen Cedex
ZIP/Postal Code
76031
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pascale Schneider, M.D.
Facility Name
CHU De La Réunion - Site Nord (Hôpital Félix GUYON)
City
Saint-Denis
ZIP/Postal Code
97400
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yves Reguerre, M.D.
Facility Name
CHU Saint Etienne Hôpital Nord
City
Saint-Étienne
ZIP/Postal Code
42055
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sandrine Thouvenin-Doulet, M.D.
Facility Name
CHU Strasbourg -Hôpital de Hautepierre
City
Strasbourg Cedex
ZIP/Postal Code
67098
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Catherine Paillard, M.D.
Facility Name
CHU Toulouse
City
TOULOUSE Cedex 9
ZIP/Postal Code
31059
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marlène Pasquet, M.D.
Facility Name
CHRU Tours- Hôpital Clocheville
City
Tours
ZIP/Postal Code
37000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Julien Lejeune, M.D.
Facility Name
CHU de Nancy - Hôpital de Brabois Enfant
City
Vandoeuvre-les-nancy cedex
ZIP/Postal Code
54511
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cécile Pochon, M.D.
Facility Name
Evangelisches Klinikum Bethel
City
Bielefeld
ZIP/Postal Code
33617
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Norbert Jorch, M.D.
Facility Name
Universitätsklinikum Bonn
City
Bonn
ZIP/Postal Code
53113
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ina Hainmann
Facility Name
Klinikum Bremen Mitte
City
Bremen
ZIP/Postal Code
28177
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Arnulf Pekrun, M.D.
Facility Name
Universitätsklinikum Hamburg-Eppendorf
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gabriele Escherich, M.D.
Facility Name
HELIOS Klinikum Krefeld
City
Krefeld
ZIP/Postal Code
47805
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thomas Imschweiler, M.D.
Facility Name
Universitätsmedizin Mainz
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jörg Faber, M.D.
Facility Name
Landspitali University Hospital, Children's Hospital
City
Reykjavík
ZIP/Postal Code
101
Country
Iceland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ólafur G. Jónsson, M.D.
Facility Name
Our Lady's Children's Hospital
City
Dublin
Country
Ireland
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Owen Smith, M.D.
Facility Name
Children's Hospital, Affiliate of Vilnius University Hospital Santaros Klinikos
City
Vilnius
ZIP/Postal Code
08661
Country
Lithuania
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Goda Vaitkeviciene, M.D.
Facility Name
Vilnius University Hospital Santaros Klinikos
City
Vilnius
ZIP/Postal Code
08661
Country
Lithuania
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Laimonas Griskevicius, M.D.
Facility Name
University Medical Center Utrecht, Dept of Hematology
City
Utrecht
ZIP/Postal Code
3584 CX
Country
Netherlands
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lotte van der Wagen
Facility Name
Princess Máxima Center for Pediatric Oncology
City
Utrecht
ZIP/Postal Code
3584
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Inge van der Sluis, M.D.
Facility Name
University Medical Center Utrecht
City
Utrecht
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lotte van der Wagen, M.D.
Facility Name
Haukeland University Hospital, Dept of Haematology
City
Bergen
ZIP/Postal Code
5021
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nessar Ahmad Azrakhsh, M.D.
Facility Name
Haukeland University Hospital, Dept of Paediatrics
City
Bergen
ZIP/Postal Code
5021
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anita Andrejeva, M.D.
Facility Name
Oslo University Hospital, Dept of Haematology
City
Oslo
ZIP/Postal Code
0372
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hilde Skuterud Wik, M.D.
Facility Name
Oslo University Hospital, Dept of paediatric haemato- and oncology
City
Oslo
ZIP/Postal Code
0424
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Inga Maria Johannsdottir, M.D.
Facility Name
Stavanger University Hospital, Dept of Haematology
City
Stavanger
ZIP/Postal Code
4011
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Waleed Majeed Mohammed, M.D.
Facility Name
University Hospital North Norway, Dept of Haematology
City
Tromsø
ZIP/Postal Code
9019
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lars Horvei, M.D.
Facility Name
University Hospital of North Norway, Dept of Paediatrics
City
Tromsø
ZIP/Postal Code
9038
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Simon Kranz, M.D.
Facility Name
St. Olavs University Hospital, Dept of Paediatrics
City
Trondheim
ZIP/Postal Code
7006
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bendik Lund, M.D.
Facility Name
St. Olavs University Hospital, Dept of Haematology
City
Trondheim
ZIP/Postal Code
7030
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Petter Quist-Paulsen, M.D.
Facility Name
Centro Hospitalar e Universitário de Coimbra, EPE - Hospital Pediátrico de Coimbra
City
Coimbra
ZIP/Postal Code
3000-602
Country
Portugal
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Manuel Brito, M.D.
Facility Name
Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE
City
Lisboa
ZIP/Postal Code
1099-023
Country
Portugal
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joaquin Duarte, M.D.
Facility Name
Instituto Português de Oncologia do Porto Francisco Gentil, EPE
City
Porto
ZIP/Postal Code
4200-072
Country
Portugal
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vitor Costa, M.D.
Facility Name
Sahlgrenska University Hospital, Section for Haematology and coagulation
City
Gothenburg
ZIP/Postal Code
41345
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stella Wei, M.D.
Facility Name
Sahlgrenska University Hospital, Dept of Paediatric Haematology and Oncology
City
Gothenburg
ZIP/Postal Code
41685
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jonas Abrahamsson, M.D.
Facility Name
Linköping University Hospital, Dept of Haematology
City
Linköping
ZIP/Postal Code
58185
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thomas Erger, M.D.
Facility Name
Linköping University Hospital, Dept of Paediatrics
City
Linköping
ZIP/Postal Code
58185
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hartmut Vogt, M.D.
Facility Name
Skåne University Hospital, Dept of Haematology
City
Lund
ZIP/Postal Code
22185
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Beata Tomaszewska-Toporska, M.D.
Facility Name
Skåne University Hospital, Dept of Paediatrics
City
Lund
ZIP/Postal Code
22185
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anders Castor, M.D.
Facility Name
Karolinska University Hospital, Dept of Paediatric Oncology and Haematology
City
Stockholm
ZIP/Postal Code
17176
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Johan Malmros, M.D.
Facility Name
Karolinska University Hospital, Patient area Haematology
City
Stockholm
ZIP/Postal Code
17176
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joel Joelsson, M.D.
Facility Name
Norrland University Hospital, Dept of Haematology
City
Umeå
ZIP/Postal Code
90185
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antonio Izarra, M.D.
Facility Name
Norrland University Hospital, Dept of Paediatrics
City
Umeå
ZIP/Postal Code
90185
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ulrika Norén Nyström, M.D.
Facility Name
Uppsala University Hospital, Dept of Haematology
City
Uppsala
ZIP/Postal Code
75185
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Helene Hallböök, M.D.
Facility Name
Uppsala University Hospital, Dept of Paediatric Haematology and Oncology
City
Uppsala
ZIP/Postal Code
75185
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Arja Harila-Saari, M.D.
Facility Name
Örebro University Hospital, Section for Haematology
City
Örebro
ZIP/Postal Code
70185
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Piotr Kozlowski, M.D.
Facility Name
Aberdeen Royal Infirmary, Aberdeen
City
Aberdeen
ZIP/Postal Code
AB25 2ZN
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gordon Taylor, M.D.
Facility Name
Royal Aberdeen Children's Hospital, Aberdeen
City
Aberdeen
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gordon Taylor, M.D.
Facility Name
Royal Belfast Hospital for Sick Children, Belfast
City
Belfast
ZIP/Postal Code
BT12 6BA
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christine Macartney, M.D.
Facility Name
Belfast City Hospital, Belfast
City
Belfast
ZIP/Postal Code
BT9 7AB
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Damian Finnegan, M.D.
Facility Name
The Queen Elizabeth Hospital, Birmingham
City
Birmingham
ZIP/Postal Code
B15 2TH
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lindsay George, M.D.
Facility Name
Birmingham Children's Hospital, Birmingham
City
Birmingham
ZIP/Postal Code
B4 6NH
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jayashree Motwani, M.D.
Facility Name
Bristol Royal Hospital for Children / Bristol Haematology and Oncology Centre
City
Bristol
ZIP/Postal Code
BS2 8BJ
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
John Moppett, M.D.
First Name & Middle Initial & Last Name & Degree
Katharine Hodby, M.D.
Facility Name
Addenbrooke's Hospital, Cambridge
City
Cambridge
ZIP/Postal Code
CB2 0QQ
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael Gattens, M.D.
Facility Name
Noah's Ark Children's Hospital for Wales, Cardiff
City
Cardiff
ZIP/Postal Code
CF14 4XW
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Indu Thakur, M.D.
Facility Name
University Hospital of Wales, Cardiff
City
Cardiff
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Clare Rowntree, M.D.
Facility Name
Ninewells Hospital, Dundee
City
Dundee
ZIP/Postal Code
DD1 9SY
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sudir Tauro, M.D.
Facility Name
Western General Hospital, Edinburgh
City
Edinburgh
ZIP/Postal Code
EH2 2XU
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peter Johnson, M.D.
Facility Name
Royal Hospital for Children and Young People, Edinburgh
City
Edinburgh
ZIP/Postal Code
EH9 1LF
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Susan Baird, M.D.
Facility Name
Beatson West of Scotland Cancer Centre, Glasgow
City
Glasgow
ZIP/Postal Code
G12 0YN
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nicholas Heaney, M.D.
Facility Name
Royal Hospital for Children, Glasgow
City
Glasgow
ZIP/Postal Code
G51 4TF
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Brenda Gibson, M.D.
Facility Name
Leeds General Infirmary, Leeds
City
Leeds
ZIP/Postal Code
LS1 3EX
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Danielle Ingham, M.D.
Facility Name
Leeds St James University Hospital
City
Leeds
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Richard Kelly, M.D.
Facility Name
Leicester Royal Infirmary, Leicester
City
Leicester
ZIP/Postal Code
LE1 5WW
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kaljit Bhuller, M.D.
Facility Name
Alder Hey Children's Hospital, Liverpool
City
Liverpool
ZIP/Postal Code
L12 2AP
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christopher Howell, M.D.
Facility Name
The Clatterbridge Cancer Centre NHS Foundation Trust
City
Liverpool
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Arpad Toth, M.D.
Facility Name
University College London Hospital, London
City
London
ZIP/Postal Code
NW1 2BU
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rachael Hough, M.D.
Facility Name
Great Ormond Street Hospital for Children, London
City
London
ZIP/Postal Code
WC1N 3JH
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sujith Samarasinghe, M.D.
Facility Name
King's College Hospital
City
London
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Deborah Yallop, M.D.
Facility Name
St. Bartholomews Hospital
City
London
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bela Wrench, M.D.
Facility Name
Royal Manchester Children's Hospital, Manchester
City
Manchester
ZIP/Postal Code
M13 9WL
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
John Grainger, M.D.
Facility Name
The Christie NHS Foundation Trust (PTC)
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anna Castleton, M.D.
Facility Name
Royal Victoria Infirmary, Newcastle
City
Newcastle upon Tyne
ZIP/Postal Code
NE1 4LP
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Geoff Shenton, M.D.
Facility Name
Freeman Hospital, Newcastle
City
Newcastle
ZIP/Postal Code
NE7 7DN
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tobias Menne, M.D.
Facility Name
Nottingham City Hospital, Nottingham
City
Nottingham
ZIP/Postal Code
NG5 1PB
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrew McMillan, M.D.
Facility Name
Nottingham Queen's Medical Centre
City
Nottingham
ZIP/Postal Code
NG7 2UH
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Simone Stockley, M.D.
Facility Name
Churchill Hospital, Oxford
City
Oxford
ZIP/Postal Code
OX3 7LE
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andy Peniket, M.D.
Facility Name
John Radcliffe Hospital, Oxford
City
Oxford
ZIP/Postal Code
OX3 9DU
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amrana Qureshi, M.D.
Facility Name
Derriford Hospital
City
Plymouth
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hannah Hunter, M.D.
Facility Name
Royal Hallamshire Hospital, Sheffield
City
Sheffield
ZIP/Postal Code
S10 2JF
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nick Morley, M.D.
Facility Name
Sheffield Children's Hospital, Sheffield
City
Sheffield
ZIP/Postal Code
S10 2TH
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jeanette Payne, M.D.
Facility Name
Southampton General Hospital, Southampton
City
Southampton
ZIP/Postal Code
SO16 6YD
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Juliet Gray, M.D.
Facility Name
Royal Stoke University Hospital, Stoke
City
Stoke
ZIP/Postal Code
ST4 6QG
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Deepak Chandra, M.D.
Facility Name
Royal Marsden Hospital, Sutton
City
Sutton
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Caroline Furness, M.D.

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
ALLTogether Data Sharing Policy FINAL VERSION 1.0 DATED 12APRIL2022 applies (full details available from Trial Central Office): Policy The ALLTogether Consortium aims to maximise the availability of research data to the academic community for academic non-commercial research purposes with as few restrictions as possible. All research papers should be open access whenever possible. Clinical data: The ALLTogether Consortium will consider requests for individual participant data (IPD) that underlie published results after deidentification. Requests for access for unpublished data will also be considered on a case-by-case basis. ALLTogether scientific data underpinning basic science/translational research papers should be made available to other researchers in the ALLTogether consortium and requests from academic researchers outside the consortium for access to scientific datasets should be addressed to the lead investigator of the ALLTogether study.
IPD Sharing Time Frame
The ALLTogether Consortium will consider requests for individual participant data (IPD) that underlie published results after deidentification. Requests for access for unpublished data will also be considered on a case-by-case basis.
IPD Sharing Access Criteria
Data access requests will be reviewed by The ALLTogether Board and, when applicable the ALLTogether Scientific committee. IPD will only be released if all personalised identifiers can be removed and for the sole use of the approved request (tertiary dissemination will not be permitted). Requestors will be required to sign a Data Access Agreement.
Citations:
PubMed Identifier
28819280
Citation
Toft N, Birgens H, Abrahamsson J, Griskevicius L, Hallbook H, Heyman M, Klausen TW, Jonsson OG, Palk K, Pruunsild K, Quist-Paulsen P, Vaitkeviciene G, Vettenranta K, Asberg A, Frandsen TL, Marquart HV, Madsen HO, Noren-Nystrom U, Schmiegelow K. Results of NOPHO ALL2008 treatment for patients aged 1-45 years with acute lymphoblastic leukemia. Leukemia. 2018 Mar;32(3):606-615. doi: 10.1038/leu.2017.265. Epub 2017 Aug 18.
Results Reference
background
PubMed Identifier
29966458
Citation
Schramm F, Zimmermann M, Jorch N, Pekrun A, Borkhardt A, Imschweiler T, Christiansen H, Faber J, Feuchtinger T, Schmid I, Beron G, Horstmann MA, Escherich G. Daunorubicin during delayed intensification decreases the incidence of infectious complications - a randomized comparison in trial CoALL 08-09. Leuk Lymphoma. 2019 Jan;60(1):60-68. doi: 10.1080/10428194.2018.1473575. Epub 2018 Jul 3.
Results Reference
background
PubMed Identifier
28751566
Citation
Mondelaers V, Suciu S, De Moerloose B, Ferster A, Mazingue F, Plat G, Yakouben K, Uyttebroeck A, Lutz P, Costa V, Sirvent N, Plouvier E, Munzer M, Poiree M, Minckes O, Millot F, Plantaz D, Maes P, Hoyoux C, Cave H, Rohrlich P, Bertrand Y, Benoit Y; Children-s Leukemia Group (CLG) of the European Organization for Research and Treatment of Cancer (EORTC). Prolonged versus standard native E. coli asparaginase therapy in childhood acute lymphoblastic leukemia and non-Hodgkin lymphoma: final results of the EORTC-CLG randomized phase III trial 58951. Haematologica. 2017 Oct;102(10):1727-1738. doi: 10.3324/haematol.2017.165845. Epub 2017 Jul 27.
Results Reference
background
PubMed Identifier
23395119
Citation
Vora A, Goulden N, Wade R, Mitchell C, Hancock J, Hough R, Rowntree C, Richards S. Treatment reduction for children and young adults with low-risk acute lymphoblastic leukaemia defined by minimal residual disease (UKALL 2003): a randomised controlled trial. Lancet Oncol. 2013 Mar;14(3):199-209. doi: 10.1016/S1470-2045(12)70600-9. Epub 2013 Feb 7.
Results Reference
background
PubMed Identifier
27269950
Citation
Pieters R, de Groot-Kruseman H, Van der Velden V, Fiocco M, van den Berg H, de Bont E, Egeler RM, Hoogerbrugge P, Kaspers G, Van der Schoot E, De Haas V, Van Dongen J. Successful Therapy Reduction and Intensification for Childhood Acute Lymphoblastic Leukemia Based on Minimal Residual Disease Monitoring: Study ALL10 From the Dutch Childhood Oncology Group. J Clin Oncol. 2016 Aug 1;34(22):2591-601. doi: 10.1200/JCO.2015.64.6364. Epub 2016 Jun 6.
Results Reference
background
PubMed Identifier
35501736
Citation
Toksvang LN, Als-Nielsen B, Bacon C, Bertasiute R, Duarte X, Escherich G, Helgadottir EA, Johannsdottir IR, Jonsson OG, Kozlowski P, Langenskjold C, Lepik K, Niinimaki R, Overgaard UM, Punab M, Raty R, Segers H, van der Sluis I, Smith OP, Strullu M, Vaitkeviciene G, Wik HS, Heyman M, Schmiegelow K. Thiopurine Enhanced ALL Maintenance (TEAM): study protocol for a randomized study to evaluate the improvement in disease-free survival by adding very low dose 6-thioguanine to 6-mercaptopurine/methotrexate-based maintenance therapy in pediatric and adult patients (0-45 years) with newly diagnosed B-cell precursor or T-cell acute lymphoblastic leukemia treated according to the intermediate risk-high group of the ALLTogether1 protocol. BMC Cancer. 2022 May 2;22(1):483. doi: 10.1186/s12885-022-09522-3.
Results Reference
derived

Learn more about this trial

A Treatment Study Protocol for Participants 0-45 Years With Acute Lymphoblastic Leukaemia

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