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International Randomised Phase III Clinical Trial in Children With Acute Myeloid Leukaemia (Myechild01)

Primary Purpose

Acute Myeloid Leukaemia

Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Gemtuzumab ozogamicin
Liposomal daunorubicin
Mitoxantrone
Fludarabine
Cytarabine
Busulfan
Cyclophosphamide
Sponsored by
University of Birmingham
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukaemia focused on measuring Acute Myeloid Leukaemia, Children, Gemtuzumab ozogamicin, Liposomal daunorubicin, Mitoxantrone, Randomised controlled trial, Risk stratification, Minimal residual disease, Stem cell transplant

Eligibility Criteria

undefined - 17 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Inclusion criteria for trial entry

  • Diagnosis of acute myeloid leukaemia (AML) /high risk Myelodysplastic syndrome (MDS) (>10% blasts in the bone marrow)/isolated myeloid sarcoma (MS) (either de novo or secondary).
  • Age <18 years at trial entry.
  • No prior chemotherapy or biological therapy for AML/high risk MDS/isolated MS other than that permitted in the protocol.
  • Normal cardiac function defined as fractional shortening ≥28% or ejection fraction ≥55%.
  • Fit for protocol chemotherapy.
  • Documented negative pregnancy test for female patients of childbearing potential.
  • Patient agrees to use effective contraception (patients of child bearing potential).
  • Written informed consent from the patient and/or parent/legal guardian.

Inclusion criteria for participation in the gemtuzumab ozogamicin dose finding study:

Centres must be formally activated in order to be take part in the embedded dose escalation study. Please contact the trial office for further information.

  • Patient meets the inclusion criteria for trial entry.
  • Age:

    • ≥12 months for the major dose finding study
    • ≥ 12 weeks and <12 months for the minor dose finding study
  • Normal renal function defined as calculated creatinine clearance ≥90ml/min/1.73m2.
  • Normal hepatic function defined as total bilirubin ≤2.5 upper limit of normal (ULN) for age unless it is caused by leukaemic involvement or Gilbert's syndrome or similar disorder.
  • Alanine transaminase (ALT) or aspartate transaminase (AST) ≤10 x ULN for age.
  • Written informed consent from the patient and/or parent/legal guardian.

Inclusion criteria for treatment with gemtuzumab ozogamicin for patients not participating in the gemtuzumab ozogamicin dose finding study or R2.

  • Patient meets the inclusion criteria for trial entry (section 4.1.1)
  • Age:

    • ≥12 months
    • ≥ 12 weeks
    • ≥28 days and <12 weeks (patients will receive a maximum of one dose of gemtuzumab ozogamicin)
  • Normal renal function, defined as calculated creatinine clearance ≥90 ml/min/1.73m2
  • Normal hepatic function, defined as total bilirubin ≤2.5 upper limit of normal (ULN) for age and not due to leukaemic involvement or Gilbert's syndrome or similar disorder
  • ALT or AST ≤10 x ULN for age
  • Written informed consent from the patient and/or parent/legal guardian

Inclusion criteria for participation in R2.(once open to randomisation in the applicable age group)

• Patient meets the inclusion criteria for trial entry

Patient age:

  • ≥12 months
  • ≥12 weeks (once R2 open in patients aged ≥12 weeks and <12 months)
  • Normal renal function defined as calculated creatinine clearance ≥90ml/min/1.73m2.
  • Normal hepatic function defined as total bilirubin ≤2.5 ULN for age and not due to leukaemic involvement or Gilbert's syndrome or similar disorder.
  • ALT or AST ≤10 x ULN for age.
  • Written informed consent from the patient and/or parent/legal guardian.

Inclusion criteria for participation in R3.

  • Patient meets the inclusion criteria for trial entry
  • Induction treatment as per MyeChild 01 protocol or treated with 2 courses of mitoxantrone & cytarabine off trial.
  • Minimal residual disease (MRD) response (performed in MyeChild 01 centralised laboratories, see national MyeChild 01 Laboratory Manual):

    • Patients with good risk cytogenetics/molecular genetics and a MRD level <0.1% by flow after course 2, or a decrease in transcript levels of >3 logs after course 2 for those with an informative molecular marker, but without an informative marker of sufficient sensitivity for flow MRD monitoring or
    • Patients with intermediate risk cytogenetics/molecular genetics with a MRD level <0.1% by flow after course 1 and course 2, or a decrease in transcript levels of >3 logs after course 1 and course 2 for those with an informative molecular marker, but without an informative marker of sufficient sensitivity for flow MRD monitoring.
  • Written informed consent from the patient and/or parent/legal guardian.

Inclusion criteria for participation in R4.

  • Patient meets the inclusion criteria for trial entry
  • Induction treatment as per MyeChild 01 protocol or treated with 1 or 2 courses of mitoxantrone & cytarabine ± treatment intensification with fludarabine, cytarabine & idarubicin (FLA-Ida) off trial.
  • Patient is in complete remission (CR) or CR with incomplete blood count recovery (CRi) defined as <5% blasts confirmed by flow cytometry/ molecular/FISH in a bone marrow aspirate taken within 6 weeks prior to randomisation to R4.
  • Patient meets one of the following criteria and is a candidate for HSCT as per the protocol:

    • High risk after course 1 (all patients with poor risk cytogenetics and patients with intermediate risk cytogenetics who fail to achieve CR/CRi).
    • Intermediate risk cytogenetics with MRD >0.1% after course 1 and 2 measured by flow. If no flow MRD marker of sufficient sensitivity is identified, a molecular MRD marker with a sensitivity of >0.1% may be used.
    • Good risk cytogenetics with flow MRD >0.1% confirmed by a decrease in molecular MRD of <3 logs or rising transcript levels after course 3 despite treatment intensification (FLA-Ida) and after discussion with the Clinical Co-ordinators.
  • Availability of a 9-10/10 human leukocyte antigen (HLA) matched family or unrelated donor or 5-8/8 matched cord blood unit with an adequate cell dose as defined by the protocol section 17.1.
  • Written informed consent from the patient and/or parent/legal guardian.

Exclusion Criteria:

Exclusion criteria for all randomisations

  • Acute Promyelocytic Leukaemia.
  • Myeloid Leukaemia of Down Syndrome.
  • Blast crisis of chronic myeloid leukaemia.
  • Relapsed or refractory AML.
  • Bone marrow failure syndromes.
  • Prior anthracycline exposure which would inhibit the delivery of study anthracyclines.
  • Concurrent treatment or administration of any other experimental drug or with any other biological therapy for AML/high risk MDS/isolated MS.
  • Pregnant or lactating females.

Sites / Locations

  • Women and Children's Hospital AdelaideRecruiting
  • Queensland Children's HospitalRecruiting
  • Monash Children's HospitalRecruiting
  • Royal Childrens HospitalRecruiting
  • John Hunter Children's HopsitalRecruiting
  • Perth Children's HospitalRecruiting
  • Sydney Children's HospitalRecruiting
  • The Childrens Hospital At WestmeadRecruiting
  • Centre Hospitalier Universitaire Amiens - PicardieRecruiting
  • Centre Hospitalier Universitaire D'angersRecruiting
  • Centre Hospitalier Regional Universitaire Besancon - Hopital Jean MinjozRecruiting
  • Centre Hospitalier Universitaire De Bordeaux - Hopital PellegrinRecruiting
  • Centre Hospitalier Regional Universitaire Brest - Hopital MorvanRecruiting
  • Centre Hospitalier Universitaire De CaenRecruiting
  • Centre Hospitalier Universitaire De Clermont-ferrandRecruiting
  • Centre Hospitalier Universitaire Dijon Bourgogne - Hopital D'enfantsRecruiting
  • Centre Hospitalier Universitaire De GrenobleRecruiting
  • Hopital Jeanne Dr FlandreRecruiting
  • Centre Hospitalier Universitaire De LimogesRecruiting
  • Centre Leon BerardRecruiting
  • Hopital De La TimoneRecruiting
  • Centre Hospitalier Regional Universitaire Montpellier - Hopital Arnaud-de-villeneuveRecruiting
  • Centre Hospitalier Universitaire De NancyRecruiting
  • Centre Hospitalier Universitaire De NantesRecruiting
  • Centre Hospitalier Universitaire De NICERecruiting
  • Hopital Armand TrousseauRecruiting
  • Hopital Robert DebreRecruiting
  • Hopital Saint LouisRecruiting
  • Centre Hospitalier Universitaire De PoitiersRecruiting
  • Chu De ReimsRecruiting
  • Centre Hospitalier Universitaire De Rennes - Hopital SudRecruiting
  • Centre Hospitalier Universitaire De RouenRecruiting
  • Centre Hospitalier Universitaire Saint-etienneRecruiting
  • Strasbourg HautepierreRecruiting
  • Centre Hospitalier Universitaire De Toulouse - Hopital Des EnfantsRecruiting
  • Centre Hospitalier Regional Universitaire De Tours - Hopital ClochevilleRecruiting
  • Our Lady's Hospital for Sick ChildrenRecruiting
  • Starship Childrens HospitalRecruiting
  • Christchurch HospitalRecruiting
  • Kantonsspital AarauRecruiting
  • Universitäts-Kinderspital beiderRecruiting
  • Ospedale San GiovanniRecruiting
  • Inselspital BernRecruiting
  • Hug Hopitaux Universitaires De GeneveRecruiting
  • Centre Hospitalier Universitaire Vaudois Chuv LausanneRecruiting
  • Luzerner Kantonspital - Kinderspital LuzernRecruiting
  • Ostschweizer KinderspitalRecruiting
  • University Children's Hospital ZurichRecruiting
  • Royal Belfast Hospital for Sick ChildrenRecruiting
  • Royal Aberdeen Children's HospitalRecruiting
  • Aberdeen Royal Infirmary, NHS GrampianRecruiting
  • Birmingham Children's Hospital NHS Foundation TrustRecruiting
  • University Hospitals Bristol NHS Foundation TrustRecruiting
  • Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation TrustRecruiting
  • Cardiff and Vale University Health Board, Noah's Ark Children's Hospital for WalesRecruiting
  • NHS Lothian, Royal Hospital for Sick ChildrenRecruiting
  • NHS Greater Glasgow and Clyde, The Royal Hospital for ChildrenRecruiting
  • Leeds General Infirmary, Leeds Teaching Hospitals NHS TrustRecruiting
  • Alder Hey Children's NHS Foundation TrustRecruiting
  • University College London Hospitals NHS Foundation TrustRecruiting
  • The Royal Marsden NHS Foundation TrustRecruiting
  • Great Ormond Street Hospital For Children NHS TrustRecruiting
  • Royal Manchester Childrens' Hospital , Central Manchester University Hospitals NHS Foundation TrustRecruiting
  • The Newcastle Upon Tyne Hospitals NHS Foundation TrustRecruiting
  • Nottingham University Hospitals NHS TrustRecruiting
  • John Radcliffe Hospital, Oxford Radcliffe Hospitals NHS TrustRecruiting
  • Sheffield Children's NHS Foundation TrustRecruiting
  • Southampton University Hospitals NHS TrustRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Active Comparator

Experimental

Experimental

Active Comparator

Experimental

Active Comparator

Experimental

Arm Label

Mitoxantrone

Liposomal daunorubicin

Gemtuzumab Ozogamicin Dose Finding Study

High dose cytarabine

Fludarabine & cytarabine

Myeloablative conditioning

Reduced intensity conditioning

Arm Description

Course 1 Mitoxantrone: 12 mg/m2 daily by IV infusion over 1 hour on days 1, 2, 3 and 4 (total 4 doses). Cytarabine:100 mg/m2 12 hourly by IV bolus on days 1-10 inclusive (total 20 doses). Course 2 Mitoxantrone: 12 mg/m2 daily by IV infusion over 1 hour on days 1, 2 and 3 (total 3 doses). Cytarabine: 100 mg/m2 12 hourly by IV bolus on days 1-8 inclusive (total 16 doses).

Randomisation 1 (R1)) closed early to recruitment on 8th September 2017, due to liposomal daunorubicin manufacturing issues resulting in unavailability of the drug. Course 1 Liposomal daunorubicin: 80 mg/m2 daily by 1 hour IV infusion on days 1, 3 and 5 (total 3 doses). Cytarabine: 100 mg/m2 12 hourly by IV bolus on days 1-10 inclusive (total 20 doses). Course 2 Liposomal daunorubicin: 60 mg/m2 daily by 1 hour IV infusion on days 1, 3 and 5 (total 3 doses). Cytarabine: 100 mg/m2 12 hourly by IV bolus on days 1-8 inclusive (total 16 doses).

Cohort 1: 1x3mg/m2 IV infusion over 2hours on day 4. Cohort 2: 2x3mg/m2 IV infusion over 2hours on day 4 and day 7. Cohort 3: 3x3mg/m2 IV infusion over 2hours on days 4, 7 and 10.

Two courses of Cytarabine: 3 g/m2 12 hourly by IV infusion over 4 hours on days 1, 3 and 5 (total 6 doses).

Two courses of: Fludarabine: 30 mg/m2 daily by IV infusion over 30 minutes on days 1-5 inclusive (total 5 doses). Cytarabine: 2 g/m2 daily by IV infusion over 4 hours on days 1-5 inclusive (total 5 doses).The cytarabine infusion should be started 4 hours after the start of the fludarabine infusion

Busulfan Area Under the Curve (AUC) 70-100mg/L x hr by IV infusion over 3 hours, given 12 hourly on days -10 to -7 (8 doses). Cyclophosphamide 50mg/kg/day by IV infusion over 1 hour, on days -5 to -2 (4 doses).

Busulfan AUC60-65mg/L X hr by IV infusion over 3 hours, given 12 hourly on days -5 to -2 (8 doses). Fludarabine 30mg/m2/day by IV infusion over 30 minutes on days -8 to -3 (6 doses).

Outcomes

Primary Outcome Measures

Incidence of dose limiting toxicities (DLTs).
Event Free Survival (EFS).
The primary analysis will be carried out once the last patient has a minimum of 1 year follow up. EFS estimates will be presented at 24 months along with 95% confidence intervals.
Event Free Survival (EFS).
The primary analysis will be carried out once the last patient has a minimum of 1 year follow up. EFS estimates will be presented at 24 months along with 95% confidence intervals.
Relapse free survival (RFS).
The primary analysis will be carried out once the last patient has a minimum of 1 year follow up. RFS estimates will be presented at 24 months along with 95% confidence intervals.
Early treatment related adverse reactions.
Early treatment related adverse reactions defined as the incidence by day 100 post-transplant of grade 3-5 toxicity for the following systems using the National Cancer Institute (NCI) Common Terminology Criteria v4: Cardiac (pericardial effusion/Left ventricular systolic dysfunction). Respiratory, thoracic and mediastinal (hypoxia/pneumonitis). Gastrointestinal (GI) (diarrhoea/typhlitis/upper and lower GI haemorrhage). Investigations (bilirubin). Renal and Urinary (acute kidney injury/haematuria). Nervous system (seizure).
Relapse free survival (RFS).
The primary analysis will be carried out once the last patient has a minimum of 1 year follow up. RFS estimates will be presented at 12 months along with 95% confidence intervals.

Secondary Outcome Measures

The nature, incidence and severity of adverse events (AEs) (gemtuzumab ozogamicin dose finding study).
Response measured by bone marrow assessment using morphology and minimal residual disease (MRD) assessment (gemtuzumab ozogamicin dose finding study).
Response is assessed by morphology confirmed by MRD levels measured by flow cytometry, molecular methods or fluorescence in situ hybridisation (FISH) as defined in the protocol, in combination with platelet and neutrophil counts. These results of these assessments will be combined to determine the patient's disease response using the response criteria defined in the protocol.
Serum pharmacokinetic (PK) parameters of gemtuzumab ozogamicin: Clearance (CL) (gemtuzumab ozogamicin dose finding study)
Serum PK parameters will be measured using serial samples taken at multiple timepoints during course 1 and at 1 month post first dose of gemtuzumab ozogamicin as defined in the protocol by dose cohort.
Serum pharmacokinetic (PK) parameters of gemtuzumab ozogamicin: Volume of distribution (Vd) (gemtuzumab ozogamicin dose finding study)
Serum PK parameters will be measured using serial samples taken at multiple timepoints during course 1 and at 1 month post first dose of gemtuzumab ozogamicin as defined in the protocol by dose cohort.
Complete remission (CR) (R1 & R2).
Evaluated using remission status at completion of course 1 and course 2.
Reasons for failure to achieve CR (R1 & R2).
Evaluated as resistant disease, induction death or not evaluable.This will be evaluated at completion of course 1 and 2 of treatment, once patient's blood counts have recovered or reason for non-recovery has been determined.
Cumulative Incidence of Relapse (CIR) (all randomisations).
The primary analysis will be carried out once the last patient has a minimum of 1 year follow up. CIR estimates will be presented at 24 months along with 95% confidence intervals for randomisations 1, 2 and 3, and at 12 months for randomisation 4.
Death in CR (DCR) (R1, R2 & R3).
The primary analysis will be carried out once the last patient has a minimum of 1 year follow up. DCR estimates will be presented at 24 months along with 95% confidence intervals.
Event Free Survival (EFS) (R1, R2 & R3).
The primary analysis will be carried out once the last patient has a minimum of 1 year follow up. EFS estimates will be presented at 24 months along with 95% confidence intervals.
Overall Survival (OS) (all randomisations).
The primary analysis will be carried out once the last patient has a minimum of 1 year follow up. OS estimates will be presented at 24 months along with 95% confidence intervals for randomisations 1, 2 and 3, and at 12 months for randomisation 4.
Incidence of toxicities (all randomisations).
Incidence of cardiotoxicity (R1, R2 & R4 only).
Incidence of bilirubin of grade 3 of higher (R2 & R4 only).
Incidence of Veno-Occlusive Disease (R2 & R4 only).
Minimal Residual Disease (MRD) clearance after course 1 & 2 (R1 & R2 only).
Evaluated using MRD result at completion of course 1 and 2 once patient's blood counts have recovered or reason for non-recovery has been determined.
Time to haematological recovery (all randomisations).
Evaluated using the date of haematological recovery (platelets to >=80 x 10^9/L, and neutrophils to >=1.0 x 10^9/L). The primary analysis will be carried out once the last patient has a minimum of 1 year follow up. Time to haematological recovery estimates will be presented at 45 days post course 1 and course 2 of treatment along with 95% confidence intervals.
Days in hospital after each course of treatment (all randomisations).
Total number of days spent in hospital for each course of treatment, collected from date of randomisation until count recovery after final course of treatment, up to a maximum of 45 days post the final course of treatment. This will be summarised per course of treatment.
Incidence of mixed chimerism at day 100 post-transplant (R4 only).
Treatment Related Mortality (TRM) (R4 only).
The primary analysis will be carried out once the last patient has a minimum of 1 year follow up which is estimated to be 7 years after the start of recruitment. TRM estimates will be presented at 12 months along with 95% confidence intervals.
Gonadal function (R4 only).
The method of assessment will be by scale (Tanner scale) and physiological parameters. This will be evaluated at 1 year post-transplant and at the end of study follow-up.

Full Information

First Posted
January 8, 2016
Last Updated
September 30, 2021
Sponsor
University of Birmingham
Collaborators
Assistance Publique - Hôpitaux de Paris, Cancer Research UK, National Cancer Institute, France, Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT02724163
Brief Title
International Randomised Phase III Clinical Trial in Children With Acute Myeloid Leukaemia
Acronym
Myechild01
Official Title
International Randomised Phase III Clinical Trial in Children With Acute Myeloid Leukaemia - Incorporating an Embedded Dose Finding Study for Gemtuzumab Ozogamicin in Combination With Induction Chemotherapy
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Recruiting
Study Start Date
April 2016 (Actual)
Primary Completion Date
December 2031 (Anticipated)
Study Completion Date
December 2032 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Birmingham
Collaborators
Assistance Publique - Hôpitaux de Paris, Cancer Research UK, National Cancer Institute, France, Pfizer

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The main purpose of this study is : To establish which number of doses of gemtuzumab ozogamicin (up to a maximum of 3 doses) is tolerated and can be safety delivered in combination with cytarabine plus mitoxantrone or liposomal daunorubicin in induction To compare mitoxantrone (anthracenedione) & cytarabine with liposomal daunorubicin (anthracycline) & cytarabine as induction therapy. (Randomisation 1 (R1) closed early to recruitment on 8th September 2017, due to liposomal daunorubicin manufacturing issues resulting in unavailability of the drug.) To compare a single dose of gemtuzumab ozogamicin with the optimum tolerated number of doses of gemtuzumab ozogamicin (identified by the dose-finding study) when combined with induction chemotherapy. To compare two consolidation regimens: high dose cytarabine (HD Ara-C) and fludarabine & cytarabine (FLA) in standard risk patients. To compare the toxicity and effectiveness of two haemopoietic stem cell transplant (HSCT) conditioning regimens of different intensity: conventional myeloablative conditioning (MAC) with busulfan/cyclophosphamide and reduced intensity conditioning (RIC) with fludarabine/busulfan.
Detailed Description
MyeChild 01 is an international phase III clinical trial in children with acute myeloid leukaemia (AML); a disease with significant mortality. It will compare two induction chemotherapy regimens: mitoxantrone and cytarabine (current standard treatment) with liposomal daunorubicin and cytarabine. This will test liposomal daunorubicin, which is believed to be less cardiotoxic than similar conventional drugs, although this is unproven. (Randomisation 1 (R1) closed early to recruitment on 8th September 2017, due to liposomal daunorubicin manufacturing issues resulting in unavailability of the drug.) Patients responding well to induction chemotherapy are eligible for a randomisation of two consolidation regimens: high dose cytarabine (current standard treatment) or fludarabine and cytarabine (FLA); a regimen commonly used in patients with relapsed disease, testing whether FLA is more effective in front line therapy than standard consolidation treatment. Patients with cytogenetic features associated with a higher risk of relapse and those responding sub-optimally to induction treatment are candidates for haemopoietic stem cell transplant (HSCT) and are eligible for a randomisation comparing two HSCT conditioning regimens: myeloablative conditioning (MAC) (current UNited Kingdom (UK) standard) or reduced intensity conditioning (RIC). HSCT has not consistently shown benefit in high risk patients because the mortality associated with the procedure has outweighed the advantage from a reduction in relapse risk. This will test whether reducing the intensity of conditioning improves survival by reducing transplant related deaths without increasing the relapse rate. The trial incorporates a dose finding study for gemtuzumab ozogamicin. The aim is to identify the optimum tolerated number of doses of gemtuzumab ozogamicin (up to a total of 3 doses), which can be safely combined with either of the induction chemotherapy regimens and then to compare this number of doses with one dose of gemtuzumab ozogamicin. The intensity of treatment will be directed by cytogenetics/molecular genetics and response assessed by minimal residual disease (MRD) levels measured by flow cytometry and molecular methodology.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukaemia
Keywords
Acute Myeloid Leukaemia, Children, Gemtuzumab ozogamicin, Liposomal daunorubicin, Mitoxantrone, Randomised controlled trial, Risk stratification, Minimal residual disease, Stem cell transplant

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
700 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Mitoxantrone
Arm Type
Active Comparator
Arm Description
Course 1 Mitoxantrone: 12 mg/m2 daily by IV infusion over 1 hour on days 1, 2, 3 and 4 (total 4 doses). Cytarabine:100 mg/m2 12 hourly by IV bolus on days 1-10 inclusive (total 20 doses). Course 2 Mitoxantrone: 12 mg/m2 daily by IV infusion over 1 hour on days 1, 2 and 3 (total 3 doses). Cytarabine: 100 mg/m2 12 hourly by IV bolus on days 1-8 inclusive (total 16 doses).
Arm Title
Liposomal daunorubicin
Arm Type
Experimental
Arm Description
Randomisation 1 (R1)) closed early to recruitment on 8th September 2017, due to liposomal daunorubicin manufacturing issues resulting in unavailability of the drug. Course 1 Liposomal daunorubicin: 80 mg/m2 daily by 1 hour IV infusion on days 1, 3 and 5 (total 3 doses). Cytarabine: 100 mg/m2 12 hourly by IV bolus on days 1-10 inclusive (total 20 doses). Course 2 Liposomal daunorubicin: 60 mg/m2 daily by 1 hour IV infusion on days 1, 3 and 5 (total 3 doses). Cytarabine: 100 mg/m2 12 hourly by IV bolus on days 1-8 inclusive (total 16 doses).
Arm Title
Gemtuzumab Ozogamicin Dose Finding Study
Arm Type
Experimental
Arm Description
Cohort 1: 1x3mg/m2 IV infusion over 2hours on day 4. Cohort 2: 2x3mg/m2 IV infusion over 2hours on day 4 and day 7. Cohort 3: 3x3mg/m2 IV infusion over 2hours on days 4, 7 and 10.
Arm Title
High dose cytarabine
Arm Type
Active Comparator
Arm Description
Two courses of Cytarabine: 3 g/m2 12 hourly by IV infusion over 4 hours on days 1, 3 and 5 (total 6 doses).
Arm Title
Fludarabine & cytarabine
Arm Type
Experimental
Arm Description
Two courses of: Fludarabine: 30 mg/m2 daily by IV infusion over 30 minutes on days 1-5 inclusive (total 5 doses). Cytarabine: 2 g/m2 daily by IV infusion over 4 hours on days 1-5 inclusive (total 5 doses).The cytarabine infusion should be started 4 hours after the start of the fludarabine infusion
Arm Title
Myeloablative conditioning
Arm Type
Active Comparator
Arm Description
Busulfan Area Under the Curve (AUC) 70-100mg/L x hr by IV infusion over 3 hours, given 12 hourly on days -10 to -7 (8 doses). Cyclophosphamide 50mg/kg/day by IV infusion over 1 hour, on days -5 to -2 (4 doses).
Arm Title
Reduced intensity conditioning
Arm Type
Experimental
Arm Description
Busulfan AUC60-65mg/L X hr by IV infusion over 3 hours, given 12 hourly on days -5 to -2 (8 doses). Fludarabine 30mg/m2/day by IV infusion over 30 minutes on days -8 to -3 (6 doses).
Intervention Type
Drug
Intervention Name(s)
Gemtuzumab ozogamicin
Other Intervention Name(s)
Mylotarg
Intervention Description
Antibody-conjugated chemotherapy agent.
Intervention Type
Drug
Intervention Name(s)
Liposomal daunorubicin
Intervention Description
Anthracycline (Randomisation 1 (R1)) closed early to recruitment on 8th September 2017, due to liposomal daunorubicin manufacturing issues resulting in unavailability of the drug.
Intervention Type
Drug
Intervention Name(s)
Mitoxantrone
Intervention Description
DNA-reactive agent
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
A water-soluble fluorinated nucleotide analogue of the antiviral agent vidarabine.
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Intervention Description
Pyrimidine nucleoside analogue, an antineoplastic agent.
Intervention Type
Drug
Intervention Name(s)
Busulfan
Intervention Description
Alkylsulfonate
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
A nitrogen mustard alkylating agent from the oxazaphosphorine group
Primary Outcome Measure Information:
Title
Incidence of dose limiting toxicities (DLTs).
Time Frame
Incidence of DLTs will be evaluated up to day 45 post course 1 and course 2 of induction chemotherapy.
Title
Event Free Survival (EFS).
Description
The primary analysis will be carried out once the last patient has a minimum of 1 year follow up. EFS estimates will be presented at 24 months along with 95% confidence intervals.
Time Frame
Event free survival (EFS) will be evaluated as the time from randomisation one to the first event, up to 16 years.
Title
Event Free Survival (EFS).
Description
The primary analysis will be carried out once the last patient has a minimum of 1 year follow up. EFS estimates will be presented at 24 months along with 95% confidence intervals.
Time Frame
Event free survival (EFS) will be evaluated as the time from randomisation two to the first event, up to 16 years..
Title
Relapse free survival (RFS).
Description
The primary analysis will be carried out once the last patient has a minimum of 1 year follow up. RFS estimates will be presented at 24 months along with 95% confidence intervals.
Time Frame
Relapse free survival (RFS) will be evaluated as the time of randomisation three to the first relapse or death from any cause, up to 16 years.
Title
Early treatment related adverse reactions.
Description
Early treatment related adverse reactions defined as the incidence by day 100 post-transplant of grade 3-5 toxicity for the following systems using the National Cancer Institute (NCI) Common Terminology Criteria v4: Cardiac (pericardial effusion/Left ventricular systolic dysfunction). Respiratory, thoracic and mediastinal (hypoxia/pneumonitis). Gastrointestinal (GI) (diarrhoea/typhlitis/upper and lower GI haemorrhage). Investigations (bilirubin). Renal and Urinary (acute kidney injury/haematuria). Nervous system (seizure).
Time Frame
Early treatment related adverse reactions will be evaluated at day 100 post-transplant.
Title
Relapse free survival (RFS).
Description
The primary analysis will be carried out once the last patient has a minimum of 1 year follow up. RFS estimates will be presented at 12 months along with 95% confidence intervals.
Time Frame
Relapse free survival (RFS) will be evaluated as the time of randomisation four to the first relapse or death from any cause, up to 16 years.
Secondary Outcome Measure Information:
Title
The nature, incidence and severity of adverse events (AEs) (gemtuzumab ozogamicin dose finding study).
Time Frame
Evaluated by day 45 post course 1 and course 2.
Title
Response measured by bone marrow assessment using morphology and minimal residual disease (MRD) assessment (gemtuzumab ozogamicin dose finding study).
Description
Response is assessed by morphology confirmed by MRD levels measured by flow cytometry, molecular methods or fluorescence in situ hybridisation (FISH) as defined in the protocol, in combination with platelet and neutrophil counts. These results of these assessments will be combined to determine the patient's disease response using the response criteria defined in the protocol.
Time Frame
Evaluated by day 45 post course 1 and course 2.
Title
Serum pharmacokinetic (PK) parameters of gemtuzumab ozogamicin: Clearance (CL) (gemtuzumab ozogamicin dose finding study)
Description
Serum PK parameters will be measured using serial samples taken at multiple timepoints during course 1 and at 1 month post first dose of gemtuzumab ozogamicin as defined in the protocol by dose cohort.
Time Frame
Evaluated up to one month after the first dose of gemtuzumab ozogamicin.
Title
Serum pharmacokinetic (PK) parameters of gemtuzumab ozogamicin: Volume of distribution (Vd) (gemtuzumab ozogamicin dose finding study)
Description
Serum PK parameters will be measured using serial samples taken at multiple timepoints during course 1 and at 1 month post first dose of gemtuzumab ozogamicin as defined in the protocol by dose cohort.
Time Frame
Evaluated up to one month after the first dose of gemtuzumab ozogamicin.
Title
Complete remission (CR) (R1 & R2).
Description
Evaluated using remission status at completion of course 1 and course 2.
Time Frame
Evaluated and presented at the completion of course 1 and 2 of treatment up to a maximum of 45 days post each course of treatment
Title
Reasons for failure to achieve CR (R1 & R2).
Description
Evaluated as resistant disease, induction death or not evaluable.This will be evaluated at completion of course 1 and 2 of treatment, once patient's blood counts have recovered or reason for non-recovery has been determined.
Time Frame
Evaluated and presented at the completion of course 1 and 2 of treatment, up to a maximum of 45 days post each course of treatment.
Title
Cumulative Incidence of Relapse (CIR) (all randomisations).
Description
The primary analysis will be carried out once the last patient has a minimum of 1 year follow up. CIR estimates will be presented at 24 months along with 95% confidence intervals for randomisations 1, 2 and 3, and at 12 months for randomisation 4.
Time Frame
Evaluated as time from randomisation to the relevant question to relapse, up to 16 years.
Title
Death in CR (DCR) (R1, R2 & R3).
Description
The primary analysis will be carried out once the last patient has a minimum of 1 year follow up. DCR estimates will be presented at 24 months along with 95% confidence intervals.
Time Frame
Evaluated as time from randomisation to relevant question to date of death from any cause in patients who have achieved CR, up to 16 years.
Title
Event Free Survival (EFS) (R1, R2 & R3).
Description
The primary analysis will be carried out once the last patient has a minimum of 1 year follow up. EFS estimates will be presented at 24 months along with 95% confidence intervals.
Time Frame
Evaluated as time from randomisation to the relevant question to the first of failure to achieve CR (recorded as an event on day 1), relapse, secondary malignancy or death from any cause, up to 16 years.
Title
Overall Survival (OS) (all randomisations).
Description
The primary analysis will be carried out once the last patient has a minimum of 1 year follow up. OS estimates will be presented at 24 months along with 95% confidence intervals for randomisations 1, 2 and 3, and at 12 months for randomisation 4.
Time Frame
Evaluated as time from randomisation to the relevant question to death from any cause or date last seen for patients who are alive at the end of the trial, up to 16 years.
Title
Incidence of toxicities (all randomisations).
Time Frame
Evaluated 30 days after end of trial treatment.
Title
Incidence of cardiotoxicity (R1, R2 & R4 only).
Time Frame
Evaluated 30 days after end of trial treatment.
Title
Incidence of bilirubin of grade 3 of higher (R2 & R4 only).
Time Frame
Evaluated 30 days after end of trial treatment.
Title
Incidence of Veno-Occlusive Disease (R2 & R4 only).
Time Frame
Evaluated 30 days after end of trial treatment.
Title
Minimal Residual Disease (MRD) clearance after course 1 & 2 (R1 & R2 only).
Description
Evaluated using MRD result at completion of course 1 and 2 once patient's blood counts have recovered or reason for non-recovery has been determined.
Time Frame
Evaluated and presented at completion of course 1 and 2 of treatment, up to a maximum of 45 days post each course of treatment.
Title
Time to haematological recovery (all randomisations).
Description
Evaluated using the date of haematological recovery (platelets to >=80 x 10^9/L, and neutrophils to >=1.0 x 10^9/L). The primary analysis will be carried out once the last patient has a minimum of 1 year follow up. Time to haematological recovery estimates will be presented at 45 days post course 1 and course 2 of treatment along with 95% confidence intervals.
Time Frame
Evaluated by day 45 post course 1 and course 2.
Title
Days in hospital after each course of treatment (all randomisations).
Description
Total number of days spent in hospital for each course of treatment, collected from date of randomisation until count recovery after final course of treatment, up to a maximum of 45 days post the final course of treatment. This will be summarised per course of treatment.
Time Frame
Evaluated once all patients have completed trial treatment.
Title
Incidence of mixed chimerism at day 100 post-transplant (R4 only).
Time Frame
Evaluated at day 100 post-transplant.
Title
Treatment Related Mortality (TRM) (R4 only).
Description
The primary analysis will be carried out once the last patient has a minimum of 1 year follow up which is estimated to be 7 years after the start of recruitment. TRM estimates will be presented at 12 months along with 95% confidence intervals.
Time Frame
Evaluated as time in days between randomisation to R4 and death which is unrelated to the underlying disease and considered related to the transplant procedure.
Title
Gonadal function (R4 only).
Description
The method of assessment will be by scale (Tanner scale) and physiological parameters. This will be evaluated at 1 year post-transplant and at the end of study follow-up.
Time Frame
Evaluated at 1 year post-transplant and at the end of follow-up, which is estimated to be through to study completion, an average timeframe of 10 years.

10. Eligibility

Sex
All
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Inclusion criteria for trial entry Diagnosis of acute myeloid leukaemia (AML) /high risk Myelodysplastic syndrome (MDS) (>10% blasts in the bone marrow)/isolated myeloid sarcoma (MS) (either de novo or secondary). Age <18 years at trial entry. No prior chemotherapy or biological therapy for AML/high risk MDS/isolated MS other than that permitted in the protocol. Normal cardiac function defined as fractional shortening ≥28% or ejection fraction ≥55%. Fit for protocol chemotherapy. Documented negative pregnancy test for female patients of childbearing potential. Patient agrees to use effective contraception (patients of child bearing potential). Written informed consent from the patient and/or parent/legal guardian. Inclusion criteria for participation in the gemtuzumab ozogamicin dose finding study: Centres must be formally activated in order to be take part in the embedded dose escalation study. Please contact the trial office for further information. Patient meets the inclusion criteria for trial entry. Age: ≥12 months for the major dose finding study ≥ 12 weeks and <12 months for the minor dose finding study Normal renal function defined as calculated creatinine clearance ≥90ml/min/1.73m2. Normal hepatic function defined as total bilirubin ≤2.5 upper limit of normal (ULN) for age unless it is caused by leukaemic involvement or Gilbert's syndrome or similar disorder. Alanine transaminase (ALT) or aspartate transaminase (AST) ≤10 x ULN for age. Written informed consent from the patient and/or parent/legal guardian. Inclusion criteria for treatment with gemtuzumab ozogamicin for patients not participating in the gemtuzumab ozogamicin dose finding study or R2. Patient meets the inclusion criteria for trial entry (section 4.1.1) Age: ≥12 months ≥ 12 weeks ≥28 days and <12 weeks (patients will receive a maximum of one dose of gemtuzumab ozogamicin) Normal renal function, defined as calculated creatinine clearance ≥90 ml/min/1.73m2 Normal hepatic function, defined as total bilirubin ≤2.5 upper limit of normal (ULN) for age and not due to leukaemic involvement or Gilbert's syndrome or similar disorder ALT or AST ≤10 x ULN for age Written informed consent from the patient and/or parent/legal guardian Inclusion criteria for participation in R2.(once open to randomisation in the applicable age group) • Patient meets the inclusion criteria for trial entry Patient age: ≥12 months ≥12 weeks (once R2 open in patients aged ≥12 weeks and <12 months) Normal renal function defined as calculated creatinine clearance ≥90ml/min/1.73m2. Normal hepatic function defined as total bilirubin ≤2.5 ULN for age and not due to leukaemic involvement or Gilbert's syndrome or similar disorder. ALT or AST ≤10 x ULN for age. Written informed consent from the patient and/or parent/legal guardian. Inclusion criteria for participation in R3. Patient meets the inclusion criteria for trial entry Induction treatment as per MyeChild 01 protocol or treated with 2 courses of mitoxantrone & cytarabine off trial. Minimal residual disease (MRD) response (performed in MyeChild 01 centralised laboratories, see national MyeChild 01 Laboratory Manual): Patients with good risk cytogenetics/molecular genetics and a MRD level <0.1% by flow after course 2, or a decrease in transcript levels of >3 logs after course 2 for those with an informative molecular marker, but without an informative marker of sufficient sensitivity for flow MRD monitoring or Patients with intermediate risk cytogenetics/molecular genetics with a MRD level <0.1% by flow after course 1 and course 2, or a decrease in transcript levels of >3 logs after course 1 and course 2 for those with an informative molecular marker, but without an informative marker of sufficient sensitivity for flow MRD monitoring. Written informed consent from the patient and/or parent/legal guardian. Inclusion criteria for participation in R4. Patient meets the inclusion criteria for trial entry Induction treatment as per MyeChild 01 protocol or treated with 1 or 2 courses of mitoxantrone & cytarabine ± treatment intensification with fludarabine, cytarabine & idarubicin (FLA-Ida) off trial. Patient is in complete remission (CR) or CR with incomplete blood count recovery (CRi) defined as <5% blasts confirmed by flow cytometry/ molecular/FISH in a bone marrow aspirate taken within 6 weeks prior to randomisation to R4. Patient meets one of the following criteria and is a candidate for HSCT as per the protocol: High risk after course 1 (all patients with poor risk cytogenetics and patients with intermediate risk cytogenetics who fail to achieve CR/CRi). Intermediate risk cytogenetics with MRD >0.1% after course 1 and 2 measured by flow. If no flow MRD marker of sufficient sensitivity is identified, a molecular MRD marker with a sensitivity of >0.1% may be used. Good risk cytogenetics with flow MRD >0.1% confirmed by a decrease in molecular MRD of <3 logs or rising transcript levels after course 3 despite treatment intensification (FLA-Ida) and after discussion with the Clinical Co-ordinators. Availability of a 9-10/10 human leukocyte antigen (HLA) matched family or unrelated donor or 5-8/8 matched cord blood unit with an adequate cell dose as defined by the protocol section 17.1. Written informed consent from the patient and/or parent/legal guardian. Exclusion Criteria: Exclusion criteria for all randomisations Acute Promyelocytic Leukaemia. Myeloid Leukaemia of Down Syndrome. Blast crisis of chronic myeloid leukaemia. Relapsed or refractory AML. Bone marrow failure syndromes. Prior anthracycline exposure which would inhibit the delivery of study anthracyclines. Concurrent treatment or administration of any other experimental drug or with any other biological therapy for AML/high risk MDS/isolated MS. Pregnant or lactating females.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Christina Ryan
Phone
01214151049
Email
myechild01@trials.bham.ac.uk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brenda Gibson
Organizational Affiliation
Royal Hospital for Children Glasgow
Official's Role
Principal Investigator
Facility Information:
Facility Name
Women and Children's Hospital Adelaide
City
Adelaide
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carley Purcell
Facility Name
Queensland Children's Hospital
City
Brisbane
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carley Purcell
Facility Name
Monash Children's Hospital
City
Melbourne
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carley Purcell
Facility Name
Royal Childrens Hospital
City
Melbourne
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carley Purcell
Facility Name
John Hunter Children's Hopsital
City
New Lambton Heights
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carley Purcell
Facility Name
Perth Children's Hospital
City
Perth
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carley Purcell
Facility Name
Sydney Children's Hospital
City
Sydney
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carley Purcell
Facility Name
The Childrens Hospital At Westmead
City
Westmead
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carley Purcell
Facility Name
Centre Hospitalier Universitaire Amiens - Picardie
City
Amiens
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Hospitalier Universitaire D'angers
City
Angers
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Hospitalier Regional Universitaire Besancon - Hopital Jean Minjoz
City
Besançon
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Hospitalier Universitaire De Bordeaux - Hopital Pellegrin
City
Bordeaux
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Hospitalier Regional Universitaire Brest - Hopital Morvan
City
Brest
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Hospitalier Universitaire De Caen
City
Caen
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Hospitalier Universitaire De Clermont-ferrand
City
Clermont-Ferrand
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Hospitalier Universitaire Dijon Bourgogne - Hopital D'enfants
City
Dijon
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Hospitalier Universitaire De Grenoble
City
Grenoble
Country
France
Individual Site Status
Recruiting
Facility Name
Hopital Jeanne Dr Flandre
City
Lille
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Hospitalier Universitaire De Limoges
City
Limoges
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Leon Berard
City
Lyon
Country
France
Individual Site Status
Recruiting
Facility Name
Hopital De La Timone
City
Marseille
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Hospitalier Regional Universitaire Montpellier - Hopital Arnaud-de-villeneuve
City
Montpellier
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Hospitalier Universitaire De Nancy
City
Nancy
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Hospitalier Universitaire De Nantes
City
Nantes
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Hospitalier Universitaire De NICE
City
Nice
Country
France
Individual Site Status
Recruiting
Facility Name
Hopital Armand Trousseau
City
Paris
Country
France
Individual Site Status
Recruiting
Facility Name
Hopital Robert Debre
City
Paris
Country
France
Individual Site Status
Recruiting
Facility Name
Hopital Saint Louis
City
Paris
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Hospitalier Universitaire De Poitiers
City
Poitiers
Country
France
Individual Site Status
Recruiting
Facility Name
Chu De Reims
City
Reims
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Hospitalier Universitaire De Rennes - Hopital Sud
City
Rennes
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Hospitalier Universitaire De Rouen
City
Rouen
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Hospitalier Universitaire Saint-etienne
City
Saint-Étienne
Country
France
Individual Site Status
Recruiting
Facility Name
Strasbourg Hautepierre
City
Strasbourg
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Hospitalier Universitaire De Toulouse - Hopital Des Enfants
City
Toulouse
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Hospitalier Regional Universitaire De Tours - Hopital Clocheville
City
Tours
Country
France
Individual Site Status
Recruiting
Facility Name
Our Lady's Hospital for Sick Children
City
Dublin
Country
Ireland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Corinna Phillips
Facility Name
Starship Childrens Hospital
City
Auckland
Country
New Zealand
Individual Site Status
Recruiting
Facility Name
Christchurch Hospital
City
Christchurch
Country
New Zealand
Individual Site Status
Recruiting
Facility Name
Kantonsspital Aarau
City
Aarau
Country
Switzerland
Individual Site Status
Recruiting
Facility Name
Universitäts-Kinderspital beider
City
Basel
Country
Switzerland
Individual Site Status
Recruiting
Facility Name
Ospedale San Giovanni
City
Bellinzona
Country
Switzerland
Individual Site Status
Recruiting
Facility Name
Inselspital Bern
City
Bern
Country
Switzerland
Individual Site Status
Recruiting
Facility Name
Hug Hopitaux Universitaires De Geneve
City
Geneve
Country
Switzerland
Individual Site Status
Recruiting
Facility Name
Centre Hospitalier Universitaire Vaudois Chuv Lausanne
City
Lausanne
Country
Switzerland
Individual Site Status
Recruiting
Facility Name
Luzerner Kantonspital - Kinderspital Luzern
City
Lucerne
Country
Switzerland
Individual Site Status
Recruiting
Facility Name
Ostschweizer Kinderspital
City
St. Gallen
Country
Switzerland
Individual Site Status
Recruiting
Facility Name
University Children's Hospital Zurich
City
Zurich
Country
Switzerland
Individual Site Status
Recruiting
Facility Name
Royal Belfast Hospital for Sick Children
City
Belfast
State/Province
County Antrim
ZIP/Postal Code
BT12 6BE
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Royal Aberdeen Children's Hospital
City
Aberdeen
ZIP/Postal Code
AB25 2ZG
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Aberdeen Royal Infirmary, NHS Grampian
City
Aberdeen
ZIP/Postal Code
AB25 2ZN
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Birmingham Children's Hospital NHS Foundation Trust
City
Birmingham
ZIP/Postal Code
B4 6NH
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
University Hospitals Bristol NHS Foundation Trust
City
Bristol
ZIP/Postal Code
BS1 3NU
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust
City
Cambridge
ZIP/Postal Code
CB2 0QQ
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Cardiff and Vale University Health Board, Noah's Ark Children's Hospital for Wales
City
Cardiff
ZIP/Postal Code
CF14 4XW
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
NHS Lothian, Royal Hospital for Sick Children
City
Edinburgh
ZIP/Postal Code
EH9 1LF
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
NHS Greater Glasgow and Clyde, The Royal Hospital for Children
City
Glasgow
ZIP/Postal Code
G51 4TF
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Leeds General Infirmary, Leeds Teaching Hospitals NHS Trust
City
Leeds
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Alder Hey Children's NHS Foundation Trust
City
Liverpool
ZIP/Postal Code
L12 2AP
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
University College London Hospitals NHS Foundation Trust
City
London
ZIP/Postal Code
NW1 2PG
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
The Royal Marsden NHS Foundation Trust
City
London
ZIP/Postal Code
SW3 6JJ
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Great Ormond Street Hospital For Children NHS Trust
City
London
ZIP/Postal Code
WC1N 3JH
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Royal Manchester Childrens' Hospital , Central Manchester University Hospitals NHS Foundation Trust
City
Manchester
ZIP/Postal Code
M13 9WL
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
The Newcastle Upon Tyne Hospitals NHS Foundation Trust
City
Newcastle
ZIP/Postal Code
NE7 7DN
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Nottingham University Hospitals NHS Trust
City
Nottingham
ZIP/Postal Code
NG7 2UH
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
John Radcliffe Hospital, Oxford Radcliffe Hospitals NHS Trust
City
Oxford
ZIP/Postal Code
OX3 9DU
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Sheffield Children's NHS Foundation Trust
City
Sheffield
ZIP/Postal Code
S10 2TH
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Southampton University Hospitals NHS Trust
City
Southampton
ZIP/Postal Code
SO16 6YD
Country
United Kingdom
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

International Randomised Phase III Clinical Trial in Children With Acute Myeloid Leukaemia

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