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Comparing chemotherapy treatments for children with acute myeloid leukaemia

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

PHASE3 · University of Birmingham · NCT02724163

This study is testing different chemotherapy treatments for children with acute myeloid leukaemia to see which ones are safer and more effective.

Quick facts

PhasePHASE3
Study typeInterventional
Enrollment700 (estimated)
AgesN/A to 17 Years
SexAll
SponsorUniversity of Birmingham (other)
Drugs / interventionsgemtuzumab, chemotherapy, fludarabine, cyclophosphamide
Locations68 sites (Adelaide and 67 other locations)
Trial IDNCT02724163 on ClinicalTrials.gov

What this trial studies

This international phase III clinical trial aims to evaluate the safety and effectiveness of different chemotherapy regimens in children diagnosed with acute myeloid leukaemia (AML). It compares the standard treatment of mitoxantrone and cytarabine with a potentially less cardiotoxic combination of liposomal daunorubicin and cytarabine. Additionally, the trial investigates the optimal dosing of gemtuzumab ozogamicin and compares two consolidation therapies for patients responding well to induction chemotherapy. The study also explores different conditioning regimens for patients eligible for haemopoietic stem cell transplant based on their risk factors.

Who should consider this trial

Good fit: Ideal candidates for this study are children under 18 years old diagnosed with acute myeloid leukaemia or high-risk myelodysplastic syndrome.

Not a fit: Patients with prior chemotherapy or biological therapy for AML or those with significant cardiac dysfunction may not benefit from this study.

Why it matters

Potential benefit: If successful, this trial could lead to improved treatment options and outcomes for children with acute myeloid leukaemia.

How similar studies have performed: Other studies have explored similar chemotherapy regimens, but the specific combination of liposomal daunorubicin and cytarabine in this context is relatively novel.

Eligibility criteria

Show full inclusion / exclusion 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.

Where this trial is running

Adelaide and 67 other locations

+18 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Acute Myeloid Leukaemia, Children, Gemtuzumab ozogamicin, Liposomal daunorubicin, Mitoxantrone, Randomised controlled trial, Risk stratification, Minimal residual disease

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.