International study to confirm a benefit of a combination of anti-cancer drugs in the treatment of children and young patients under age of 21 years with refractory or recurrent acute blood cancer

International randomized phase III study on the treatment of children and adolescents with refractory or relapsed acute myeloid leukemia

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2010-018980-41-BE

Enrollment

252

Registered

2013-09-20

Start date

2013-10-15

Completion date

Unknown

Last updated

2025-01-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pediatric relapsed or refractory AML MedDRA version: 18.1 Level: PT Classification code 10000880 Term: Acute myeloid leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Interventions

Product Name: gemtuzumab ozogamicin (GO) Pharmaceutical Form: Lyophilisate for solution for infusion INN or Proposed INN: GEMTUZUMAB OZOGAMICIN CAS Number: 220578-59-6 Other descriptive name: Mylotarg

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Children and adolescents =65 years) no F.1.3.1 Number of subjects for this age range 0

Exclusion criteria

Exclusion criteria: 1. Acute promyeloblastic leukemia (AML FAB type M3; please refer to your local group for the appropriate treatment protocol) 2. Myeloid Leukemia of Down syndrome (please refer to your local group for treatment alternatives) 3. Symptomatic cardiac dysfunction (CTCAEv4 grade 3 or 4) and/or a Fractional Shortening at echocardiography below 29% 4. A Karnofsky performance status 3.0 x UNL for transaminases and for bilirubin 7. History of VOD 8. History hepatitis C positivity 9. Renal impairment with creatinine < 30 ml/min 10. Decompensated hemolytic anemia 11. Hypersensitivity to GO and/or other chemotherapeutic drugs 12. Inability to potentially complete the treatment protocol for any other reason 13. Pregnant or breastfeeding patients 14. Current participation in another clinical trial for the time of first course of reinduction chemotherapy

Design outcomes

Primary

Measure	Time frame
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)	—

Measure

Time frame

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)

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Secondary

Measure	Time frame
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	—

Measure

Time frame

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

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Countries

Belgium, Czech Republic, Denmark, European Union, Germany, Hungary, Ireland, Netherlands, Serbia, Sweden

Contacts

Public ContactKatharina Waack-Buchholz

GPOH Office Essen, AML-BFM Trial Centre

waack.katharina@aml-bfm.de+4920174949611

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026