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

• Conditions: Acute Myeloid Leukaemia; Therapeutic area: Diseases [C] - Cancer [C04]; MedDRA version: 18.1Level: PTClassification code 10000880Term: Acute myeloid leukaemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2014-005066-30-GB
• Lead Sponsor: niversity of Birmingham

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-03-14
• Last Update Posted: 11 April 2016

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 700

Inclusion Criteria

Inclusion criteria for trial entry and Randomisation 1 (induction chemotherapy randomisation):
- A diagnosis of AML/high risk myelodysplastic syndrome (MDS)/isolated myeloid sarcoma (either de novo or secondary)
- Age <18 years
- No prior chemotherapy or biological therapy for AML other than that permitted in the protocol
- Normal cardiac function (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 childbearing potential)
- Written informed consent from the patient and/or parent/legal guardian

Inclusion criteria for participation in the gemtuzumab ozogamicin dose finding study:
- Patients meets the inclusion criteria for trial entry
- Age =12 months for the major dose finding study
- Age = 12 weeks and <12 months for the minor dose finding study
- Karnofsky or Lansky performance score of =50
- 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
- ALT or AST =10 x ULN for age
- Written informed consent from the patient 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):
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
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
- Written informed consent from the patient and/or parent/legal guardian

Inclusion criteria for participation in R4:
- Patient meets the eligibility criteria for trial entry
- Induction treatment as per MyeChild 01 protocol or treated with 1 or 2 courses of mitoxantrone & cytarabine ± treatment intensification with FLA-Ida off trial
- 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.
- Patient meets one of the following criteria and is a candidate for haemopoeitic stem cell transplant (HSCT) as per the protocol:
1) High risk after course 1 (all patients with poor risk cytogenetics and patients with intermediate risk cytogenetics who fail to achieve CR/CRi)
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
3) Good risk cytogenetics with flow MRD >0.1% confirmed by a decrease in molecular MRD of <3 logs or rising transcript levels after co

Exclusion Criteria

Exclusion criteria for all randomisations
- Acute promyelocytic leukaemia (APL)
- Myeloid leukaemia of Down Syndrome (ML DS)
- 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
- Pregnant or lactating females

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified