A Treatment Study Protocol for Participants 0-45 Years With Acute Lymphoblastic Leukaemia
Leukemia, Acute Lymphoblastic
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
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
No Intervention
Experimental
No Intervention
Experimental
No Intervention
Experimental
Experimental
Experimental
Experimental
Experimental
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
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.