Registrationsdatum der Studie
Einschluss der ersten teilnehmenden Person
International randomized phase III study on the treatment of children and adolescents with refractory or relapsed acute myeloid leukemia
Interventional clinical trial of medicinal product
Design der Studie
Single blind: no
Double blind: no
Parallel group: yes
Cross over: no
If controlled, specify comparator, Other Medicinial Product: no
Other specify the comparator: Standard chemotherapy treatment without IMP
Number of treatment arms in the trial: 2
Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no
Main Objective: Determination of the initial efficacy of GO when added to DX-FLA in the first course of reinduction chemotherapy in children with relapsed or refractory AML compared to DX-FLA only. Activity will be measured by the percentage of patients having not more than 20% blasts in the bone marrow (BM) before the second induction course.;
Secondary Objective: 1.Determine clinical outcome in both treatment arms, defined as refractory disease, complete remission rate after 2 reinduction courses, cumulative incidence of relapse, EFS and OS.
2.Incidence of treatment related mortality and toxicity of GO according to the CTCAEv4 when added to DX-FLA, in terms of mucosal toxicity, BM aplasia, liver toxicity with special respect to the development of VOD, also called SOS), short- and long-term cardiotoxicity and other adverse reactions, as compared to patients treated with DX-FLA only.
3.Identification of additional prognostic factors in pediatric relapsed AML, other than early treatment response, cytogenetics and duration of CR1.
4.Establish a diagnostic and logistic network to obtain an individual characterization of AML based on morphology, immunophenotype, type I and II mutations, signal pathway activation, and monitoring of MRD / treatment response for individualized stratification to targeted therapy within a short timeframe.
;Primary end point(s): The percentage of bone marrow blasts after the first course of reinduction chemotherapy on day 28” (in practice anytime between day 28 and 42 after start of first reinduction chemotherapy and before the start of the second reinduction course) given as = 20% or > 20%.;Timepoint(s) of evaluation of this end point: day 28” (before the start of the second reinduction course)
Secondary end point(s): 1. Determine incidence of refractory disease, CR/CRi rates after 2 courses and efficacy (cumulative incidence of relapse, event-free survival, and overall survival) in the different study arms
2. Determine the toxicity of GO (Mylotarg®) when added to DX-FLA in terms of BM aplasia, liver toxicity including VOD, cardiotoxicity, mucosal toxicity and other adverse reactions according to CTCAEv4 which are considered to be relevant in relapsed AML and the proposed therapy when compared to treatment with DX-FLA only.
3. Identify additional prognostic factors in pediatric relapsed AML, other than early treatment response, cytogenetics and duration of CR1.
4. Provide individual biological characterization of leukemia (morphology, immunophenotype, cytogenetics, molecular genetics and activated signalling pathways), for future individualized stratification to targeted therapy.
Timepoint(s) of evaluation of this end point: 1.: After second reinduction course
2.: Begin of treatment - Day 34 (or before the start of the second reinduction course)
3-4: Begin of treatment - after second reinduction course
Kontakt für Auskünfte
Pfizer Pharma GmbH; Deutsche José Carreras Leukämie-Stiftung e.V