Clinical Trial in Children with Acute Myeloid Leukaemia

Phase 1

• Conditions: Children and young adults up to their 18th birthday with newly diagnosed AML, high risk MDS or isolated myeloid sarcoma (MS).; MedDRA version: 20.0Level: PTClassification code 10000880Term: Acute myeloid leukaemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-005066-30-FR
• Lead Sponsor: IVERSITY OF BIRMINGHAM

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-04-27
• Last Update Posted: 5 February 2018

Recruitment & Eligibility

• Status: A
• Sex: All
• Target Recruitment: 700

Inclusion Criteria

Inclusion criteria for trial entry and R1 randomisation
. Diagnosis of AML/high risk MDS (>10% blasts in the bone marrow)/isolated MS
(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 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
Patients with reproductive potential must agree to use effective contraception during the period of therapy. Both men and women of childbearing potential should be advised to use effective contraception to avoid pregnancy up to 12 months after the last dose of study treatment. Effective contraceptive methods include hormonal and barrier contraception etc.
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:
o .12 months for the major dose finding study
o . 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fs 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 (randomisation not yet open)
. Patient meets the inclusion criteria for trial entry (section 4.1.1)
. Age .12 weeks
. 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 and not due to leukaemic involvement or Gilbertfs 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 (section 4.1.1)
. Induction treatment as per MyeChild 01 protocol or treated with 2 courses of mitoxantrone & cytarabine off trial
. 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
o 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 mee

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
• Pregnant or lactating females

Study & Design

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