Clinical trials for the treatment of acute myeloid leukemia in children and adolescents

• Register: EUCTR
• Last refreshed on: 30 April 2019
• Main ID: EUCTR2013-000018-39-DE
• Date of registration: 09/09/2014
• Prospective Registration: Yes
• Primary sponsor: Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH gGmbH)
• Public title: Clinical trials for the treatment of acute myeloid leukemia in children and adolescents
• Scientific title: Clinical trial for the treatment of acute myeloid leukemia in children and adolescents - AML-BFM 2012
• Date of first enrolment: 20/11/2014
• Target sample size: 625
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-000018-39
• 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: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Czech Republic, Germany, Slovakia, Switzerland

Contacts

• Name: AML-BFM
• Affiliation: Universitätsklinikum Essen, Kinderheilkunde III

• Name: AML-BFM
• Affiliation: Universitätsklinikum Essen, Kinderheilkunde III

Key inclusion & exclusion criteria

Inclusion criteria:
• diagnosis of AML (according to WHO classification 2008)
• Acute leukemia with mixed line assignment and myeloid dominance (MPAL; according to WHO classification 2008: included dominant myeloid biphenotypic leukemia, and acute undifferentiated leukemia (AUL))
• Age 0 to 18 years old
• Consent for study participation and for data processing and data dissemination
Are the trial subjects under 18? yes
Number of subjects for this age range: 625
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:
• Patients with acute promyelocytic leukemia / AML with t (15, 17); PML / RARA
• pre-existing conditions / syndromes which preclude treatment
• Patients with trisomy 21 and ML-DS and / or transient myeloproliferative syndrome (reference to the TMD-prevention study or the ML-DS 2006 Study)
• Acute leukemias bilineäre
• Secondary acute myeloid leukemia observation patients
• refusal of treatment
• Participation in another clinical trial, the Invention could affect the questions of this study
• Pregnancy
• Lactation
• Hypersensitivity to clofarabine
• patients of reproductive age who reject an effective pregnancy prevention
• previous treatment with cytostatic drugs for more than 14 days


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

Health Condition(s) or Problem(s) studied

AML
MedDRA version: 18.0 Level: LLT Classification code 10000886 Term: Acute myeloid leukemia System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Intervention(s)

Trade Name: Evoltra
Product Name: Evoltra
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: CLOFARABIN
CAS Number: 123318-82-1
Concentration unit: mg/ml milligram(s)/millilitre
Concentration number: 1-

Trade Name: Etopophos
Product Name: Etopophos
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Etoposid
Other descriptive name: ETOPOSIDE PHOSPHATE
Concentration unit: mg milligram(s)
Concentration number: 100-

Primary Outcome(s)

Main Objective: 1. improvement of event-free survival of children and adolescents with AML by clofarabine in combination with cytarabine and liposomal daunorubicin in the induction therapy.
2. reduction of therapy toxicity and improve quality of life by a shortened maintenance therapy without worsening the prognosis.

Secondary Objective: 3. improvement of event-free survival by a zyto-/molekulargenetisch and MRD-based risk classification. Comprehensive biological characterization to improve treatment stratification and as a basis of molecular therapeutic options.
4. Measurement of the side effects of the combined therapy of molecular active substances in combination with conventional chemotherapy.
5. detection of molecular relapse after completion of intensive chemotherapy followed by MRD monitoring in peripheral blood (up to 18 months from diagnosis)

Primary end point(s): 1: Event-free survival of patients randomized
2: Disease-free survival from randomization 2

Timepoint(s) of evaluation of this end point: After 33% have occurred or 66% of the expected under the null hypothesis events, an interim analysis of randomization 1 is performed. Four years after the end of the patients receiving the final evaluation (including final report and publication) is provided.

Secondary Outcome(s)

Secondary end point(s): Leukemia-free survival and overall survival
Disease-free survival correlated to minimal residual disease
Detection of molecular relapse
Ansprechkinetik of minimal residual disease: AML t (8, 21); inv (16), MLL rearrangement, Flt3-ITD/TDK, c-KIT mutation, NPM1, WT1 mutation
relapse incidence
Measure quality of life through toxicity monitoring

Timepoint(s) of evaluation of this end point: After 33% have occurred or 66% of the expected under the null hypothesis events, an interim analysis of randomization 1 is performed. Four years after the end of the patients receiving the final evaluation (including final report and publication) is provided.

Secondary ID(s)

AMLBFM2012

Source(s) of Monetary Support

Deutsche Krebshilfe e. V.

Ethics review

Status: Approved
Approval date:
Contact: