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

• Register: EUCTR
• Last refreshed on: 26 March 2024
• Main ID: EUCTR2010-018980-41-DK
• Date of registration: 07/11/2013
• Prospective Registration: Yes
• Primary sponsor: Hannover Medical School
• Public title: 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
• Scientific title: International randomized phase III study on the treatment of children and adolescents with refractory or relapsed acute myeloid leukemia
• Date of first enrolment: 21/11/2013
• Target sample size: 252
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-018980-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Standard chemotherapy treatment without IMP Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

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

Contacts

• Name: Prof. Dr. Dirk Reinhardt
• Affiliation: Hannover Medical School

• Name: Prof. Dr. Dirk Reinhardt
• Affiliation: Hannover Medical School

Key inclusion & exclusion criteria

Inclusion criteria:
1. Children and adolescents < 18 years of age at start of initial chemotherapy and < 21 years of age at start of this relapsed AML treatment
2. Patients with first relapsed (including relapse after SCT) or primary refractory AML
3. Signed written informed consent from patients and/or from parents or legal guardians for minor patients, according to local law and regulations
4. In female patients of childbearing potential pregnancy must be excluded.
5. Sexually active patients must be using two reliable contraception methods from the time of screening/baseline and during the study for a minimum of 3 months after the last administration of study medication. This includes every combination of a hormonal contraceptive (such as injection, transdermal patch, implant, cervical ring) or of an intrauterine device (IUD) with a barrier method (e.g. diaphragm, cervical cap, or condom) or with a spermicide.

Are the trial subjects under 18? yes
Number of subjects for this age range: 15
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 < 40% (children = 16 years) or an Lansky performance status of < 40% (children < 16 years) before start of chemotherapy
5. Any other organ dysfunction (CTCAEv4 grade 4) that will interfere with the administration of the therapy according to this protocol
6. Impaired liver function defined as > 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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Pediatric relapsed or refractory AML
MedDRA version: 14.1 Level: PT Classification code 10000880 Term: Acute myeloid leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

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
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Primary Outcome(s)

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%.

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.

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.

Timepoint(s) of evaluation of this end point: “day 28” (before the start of the second reinduction course)

Secondary Outcome(s)

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

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.

Secondary ID(s)

2010-018980-41-BE

Pediatric_Relapsed_AML2010/01

Source(s) of Monetary Support

Pfizer Pharma GmbH

Deutsche José Carreras Leukämie-Stiftung e.V

Ethics review

Status: Approved
Approval date: 21/11/2013
Contact: