MyeChild 01: Treating children with acute myeloid leukaemia

ISRCTN	ISRCTN12389567
DOI	https://doi.org/10.1186/ISRCTN12389567
ClinicalTrials.gov (NCT)	NCT02724163
Clinical Trials Information System (CTIS)	2014-005066-30
Protocol serial number	19700
Sponsor	University of Birmingham
Funder	Cancer Research UK

Submission date: 03/02/2016
Registration date: 03/02/2016
Last edited: 10/06/2025

Recruitment status: No longer recruiting
Overall study status: Ongoing
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

A trial looking at improving chemotherapy for children with acute myeloid leukaemia (MyeChild01)
https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-using-gsk2857916-for-people-with-myeloma

A study of gemtuzumab ozogamicin with chemotherapy for children with AML (MyeChild01)
https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-of-gemtuzumab-ozogamicin-with-chemotherapy-for-children-with-aml-myechild01

A trial looking at chemotherapy before a stem cell transplant for children with acute myeloid leukaemia (MyeChild01)
https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-chemotherapy-before-a-stem-cell-transplant-for-children-with-acute-myeloid

Contact information

Mr Paul Wetherell
Public

Children’s Cancer Trials Team
Cancer Research UK Clinical Trials Unit (CRCTU)
School of Medical Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom

Phone	+44 121 415 1049
Email	myechild01@trials.bham.ac.uk

Study information

Primary study design	Interventional
Study design	Randomised; Interventional; Design type: Treatment
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific 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 acronym	MyeChild 01
Study objectives	Study aims: 1. 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 2. To compare mitoxantrone (anthracenedione) and cytarabine with liposomal daunorubicin (anthracycline) & cytarabine as induction therapy 3. 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 4. To compare two consolidation regimens: high dose cytarabine (HD Ara-C) and fludarabine & cytarabine (FLA) in standard risk patients 5. 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
Ethics approval(s)	Wales REC 3, 27/10/2015, ref: 15/WA/0316
Health condition(s) or problem(s) studied	Acute myeloid leukaemia
Intervention	Current interventions as of 02/09/2021: Trial Entry Arm A Induction. Active Comparator: mitoxantrone (mitoxantrone & cytarabine) Gemtuzumab Ozogamicin Dose Finding Study Experimental: gemtuzumab ozogamicin (other names: Mylotarg) Randomisation 3 Arm C Consolidation. Active Comparator: high dose cytarabine. Arm D Consolidation. Experimental: fludarabine & cytarabine Randomisation 4 Arm E HSCT. Active Comparator: Myeloablative conditioning (busulfan & cyclophosphamide) Arm F HSCT. Experimental: Reduced intensity conditioning (busulfan & fludarabine) The Arm B Induction (Experimental: liposomal daunorubicin) closed to recruitment early on 8th September 2017, due to manufacturing issues with liposomal daunorubicin experienced by the marketing authorisation holder, which could not be rectified. Previous interventions: Randomisation 1 Arm A Induction. Active Comparator: mitoxantrone (mitoxantrone & cytarabine) Arm B Induction. Experimental: liposomal daunorubicin (liposomal daunorubicin & cytarabine) Gemtuzumab Ozogamicin Dose Finding Study Experimental: gemtuzumab ozogamicin (other names: Mylotarg) Randomisation 3 Arm C Consolidation. Active Comparator: high dose cytarabine. Arm D Consolidation. Experimental: fludarabine & cytarabine Randomisation 4 Arm E HSCT. Active Comparator: Myeloablative conditioning (busulfan & cyclophosphamide) Arm F HSCT. Experimental: Reduced intensity conditioning (busulfan & fludarabine)
Intervention type	Drug
Phase	Phase III
Drug / device / biological / vaccine name(s)	Gemtuzumab ozogamicin (Mylotarg), liposomal daunorubicin, mitoxantrone, fludarabine, cytarabine, busulfan, cyclophosphamide
Primary outcome measure(s)	Gemtuzumab ozogamicin dose finding study: Incidence of dose limiting toxicities (DLTs) are evaluated up to day 45 post course 1 and course 2 of induction chemotherapy.
Key secondary outcome measure(s)	1. Complete remission (R1 and R2) is evaluated and presented after course 1 and 2 or treatment 2. Relapse Free Survival (R3) is determined as time from randomisation 3 to first relapse or death 3. Cumulative Incidence of Relapse (all randomisations) is evaluated as time from randomisation to the relevant question of relapse 4. Days in hospital after each course of treatment (all randomisations) is evaluated once all patients have completed treatment 5. Death in complete remission (R1, R2 and R3) is evaluated as the time from randomisation to date of death from any cause in patients who achieved CR 6. Event Free Survival (R1, R2 and R3) is determined as time from randomisation to the first event 7. Nature, incidence and severity of adverse events (Gemtuzumab ozogamicin dose finding study) are evaluated by day 45 post course 1 and course 2 8. Responses measured by bone marrow assessment (Gemtuzumab ozogamicin dose finding study) on day 21-45 post day 1 of study drugs 9. Event Free Survival (R2) is determined as time from randomisation 2 to the 1st event 10. Gonadal function (R4) is evaluated at 1 year post-transplant and at the end of follow-up 11. Early Treatment Related Adverse Reactions (R4) is measured as incidence by day 100 post-transplant of grade 3-5 toxicity 12. (R4) Relapse Free Survival (R4) is determined as time from Randomisation 4 to the first relapse or death 13. Incidence of bilirubin of grade 3 of higher (R2 and R4) is evaluated 30 days after end of trial treatment 14. Incidence of cardiotoxicity (R1, R2 and R3) is evaluated 30 days after end of trial treatment 15. Incidence of mixed chimerism at day 100 post-transplant (R4) is evaluated at day 100 post-transplant 16. Incidence of toxicities (all randomisations) is evaluated 30 days after end of trial treatment 17. Incidence of Veno-Occlusive Disease(R2 and R4) is evaluated 30 days after end of trial treatment 18. Event Free Survival (R1) is determined as time from randomisation one to the first event 19. Minimal Residual Disease (MRD) clearance after course 1 and 2 (R1 and R2) is evaluated after course 1 and 2 of treatment 20. Overall survival (all randomisations) is determined as time from randomisation to death from any cause or date last seen for patients alive at end of trial 21. Reasons for failure to achieve complete remission (R1 and R2) is evaluated after course 1 and 2 of treatment 22. Clearance and Volume of Distribution (Serum pharmacokinetic parameters of gemtuzumab ozogamicin) at multiple sample time points during course 1 23. Time to haematological recovery (all randomisations) is evaluated by day 45 post course 1 and course 2.; 24. Treatment Related Mortality (R4) is evaluated as time in days between randomisation and death (considered related to the transplant)
Completion date	31/05/2032

Eligibility

Participant type(s)	Patient
Age group	Child
Upper age limit	18 Years
Sex	All
Target sample size at registration	700
Key inclusion criteria	Current participant inclusion criteria as of 02/09/2021: Inclusion criteria for trial entry: 1. A diagnosis of AML/high risk myelodysplastic syndrome (MDS)/isolated myeloid sarcoma (either de novo or secondary) 2. Aged <18 years 3. No prior chemotherapy or biological therapy for AML other than that permitted in the protocol 4. Normal cardiac function (fractional shortening ≥28% or ejection fraction of 55%) 5. Fit for protocol chemotherapy 6. Documented negative pregnancy test for patients of childbearing potential 7. Patient agrees to use effective contraception (patients of childbearing potential) 8. 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 take part in the embedded dose escalation study (please contact the trial office for further information). 1. Patient meets the inclusion criteria for trial entry 2. Aged either: 2.1. ≥12 months for the major dose finding study 2.2. ≥12 weeks and <12 months 3. Normal renal function defined as calculated creatinine clearance ≥90 ml/min/1.73m² (calculated using the BNFc formula, or that in use locally) 4. Normal hepatic function defined as total bilirubin ≤2.5 x upper limit of normal (ULN) for age unless it is caused by leukaemic involvement, Gilbert’s syndrome, or a similar disorder 5. ALT or AST ≤10 x ULN for age 6. 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: Centres must be formally activated to be able to deliver treatment with gemtuzumab ozogamicin (please contact the trial office for further information). 1. Patient meets the inclusion criteria for trial entry 2. Aged either: 2.1. ≥12 months 2.2. ≥12 weeks and <12 months 2.3. ≥28 days and and <12 weeks 3. Normal renal function defined as calculated creatinine clearance ≥90 ml/min/1.73m² (calculated using the BNFc formula, or that in use locally) 4. Normal hepatic function defined as total bilirubin ≤2.5 x upper limit of normal (ULN) for age unless it is caused by leukaemic involvement, Gilbert’s syndrome, or a similar disorder 5. ALT or AST ≤10 x ULN for age 6. 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): 1. Patient meets the inclusion criteria for trial entry 2. Aged either: 2.1. ≥12 months 2.2. ≥12 weeks and <12 months (once R2 open in patients aged ≥12 weeks and <12 months) 3. Normal renal function defined as calculated creatinine clearance ≥90 ml/min/1.73m² (calculated using the BNFc formula, or that in use locally) 4. Normal hepatic function defined as total bilirubin ≤2.5 x upper limit of normal (ULN) for age unless it is caused by leukaemic involvement, Gilbert’s syndrome, or a similar disorder 5. ALT or AST ≤10 x ULN for age 6. Written informed consent from the patient and/or parent/legal guardian Inclusion criteria for participation in R4: 1. Patient meets the inclusion criteria for trial entry 2. Induction treatment as per MyeChild 01 protocol or treated with 1 or 2 courses of mitoxantrone & cytarabine ± treatment intensification with FLA-Ida off trial 3. Patient is in CR or 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 4. Patient meets one of the following criteria and is a candidate for HSCT as per the protocol: 4.1. High risk after course 1 (all patients with poor risk cytogenetics and patients with intermediate risk cytogenetics who fail to achieve CR/CRi) 4.2. Intermediate risk cytogenetics with MRD >0.1% after courses 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 4.3. 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 (FLAIda) and after discussion with the Clinical Coordinators 5. Availability of a 9-10/10 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 6. Written informed consent from the patient and/or parent/legal guardian Previous participant inclusion criteria: Inclusion criteria for trial entry and Randomisation 1 (induction chemotherapy randomisation): 1. A diagnosis of AML/high risk myelodysplastic syndrome (MDS)/isolated myeloid sarcoma (either de novo or secondary) 2. Aged less than 18 years 3. No prior chemotherapy or biological therapy for AML other than that permitted in the protocol 4. Normal cardiac function (fractional shortening ≥28% or ejection fraction =55%) 5. Fit for protocol chemotherapy 6. Documented negative pregnancy test for female patients of childbearing potential 7. Patient agrees to use effective contraception (patients of childbearing potential) 8. Written informed consent from the patient and/or parent/legal guardian Inclusion criteria for participation in the gemtuzumab ozogamicin dose finding study: 1. Patients meets the inclusion criteria for trial entry 2. Aged ≥12 months for the major dose finding study 3. Aged ≥12 weeks and 12 months for the minor dose finding study 4. Karnofsky or Lansky performance score of =50 5. Normal renal function defined as calculated creatinine clearance =90ml/min/1.73m2 6. 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 7. ALT or AST =10 x ULN for age 8. Written informed consent from the patient or parent/legal guardian Inclusion criteria for participation in R3: 1. Patient meets the inclusion criteria for trial entry 2. Induction treatment as per MyeChild 01 protocol or treated with 2 courses of mitoxantrone & cytarabine off trial 3. Minimal residual disease (MRD) response (performed in MyeChild 01 centralised laboratories): 3.1. 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 3.2. 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 4. Written informed consent from the patient and/or parent/legal guardian Inclusion criteria for participation in R4: 1. Patient meets the eligibility criteria for trial entry 2. Induction treatment as per MyeChild 01 protocol or treated with 1 or 2 courses of mitoxantrone & cytarabine ± treatment intensification with FLA-Ida off trial 3. Patient is in CR or 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. 4. Patient meets one of the following criteria and is a candidate for haemopoeitic stem cell transplant (HSCT) as per the protocol: 4.1. High risk after course 1 (all patients with poor risk cytogenetics and patients with intermediate risk cytogenetics who fail to achieve CR/CRi) 4.2. 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 4.3. 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 (FLAIda) and after discussion with the Clinical Coordinators 5. 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 6. Written informed consent from the patient or parent/legal guardian
Key exclusion criteria	Current participant exclusion criteria as of 02/09/2021: 1. Acute promyelocytic leukaemia (APL) 2. Myeloid leukaemia of Down Syndrome (ML DS) 3. Blast crisis of chronic myeloid leukaemia 4. Relapsed or refractory AML 5. Bone marrow failure syndromes 6. Prior anthracycline exposure which would inhibit the delivery of study anthracyclines 7. Concurrent treatment or administration of any other experimental drug or with any other biological therapy for AML/high risk MDS/isolated MS 8. Pregnant or lactating Previous participant exclusion criteria: 1. Acute promyelocytic leukaemia (APL) 2. Myeloid leukaemia of Down Syndrome (ML DS) 3. Blast crisis of chronic myeloid leukaemia 4. Relapsed or refractory AML 5. Bone marrow failure syndromes 6. Prior anthracycline exposure which would inhibit the delivery of study anthracyclines 7. Concurrent treatment or administration of any other experimental drug or with any other biological therapy for AML 8. Pregnant or lactating females
Date of first enrolment	29/04/2016
Date of final enrolment	31/03/2025

Locations

Countries of recruitment

United Kingdom
England
Australia
France
Ireland
New Zealand
Switzerland

Study participating centre

University of Birmingham

Clinical Trials Unit
Edgbaston
Birmingham
B15 2TT
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	Access to this data is controlled through application to the CRCTU New Business Committee and is granted in accordance with the CRCTU Data Sharing Policy.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
HRA research summary			26/07/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Editorial Notes

10/06/2025: The following changes were made:
1. The recruitment end date was changed from 31/05/2024 to 31/03/2025.
2. The study contact was updated.
3. The Sponsor contact was changed from Cancer Research Clinical Trials Unit (CRCTU) at the University of Birmingham.
13/11/2023: The following changes have been made:
1. The recruitment end date has been changed from 31/05/2022 to 31/05/2024.
2. The drug names have been added.
26/04/2022: The following changes have been made:
1. The recruitment end date has been changed from 28/04/2022 to 31/05/2022.
2. The overall trial end date has been changed from 28/04/2032 to 31/05/2032.
3. The intention to publish date has been changed from 28/04/2033 to 31/05/2033.
02/09/2021: The following changes have been made:
1. The interventions have been updated.
2. The participant inclusion criteria have been updated.
3. The participant exclusion criteria have been updated.
4. The country of recruitment "Switzerland" has been added.
5. The publication and dissemination plan has been added.
02/11/2020: IPD sharing statement added.
27/01/2020: The public contact has been changed.
24/01/2020: Australia and New Zealand were added to the countries of recruitment.
02/04/2019: The condition has been changed from "Topic: Cancer; Subtopic: Haematological Oncology; Disease: Leukaemia (acute myeloid)" to "Acute myeloid leukaemia" following a request from the NIHR.
01/11/2017: Internal review.
25/07/2016: Cancer Help UK lay summary links added.
13/07/2016: Internal review.