AML-BFM 2012: clinical trial for the treatment of acute myeloid leukemia in children and adolescents

ISRCTN ISRCTN78830591
DOI https://doi.org/10.1186/ISRCTN78830591
EudraCT/CTIS number 2013-000018-39
Secondary identifying numbers AML-BFM2012
Submission date
05/01/2013
Registration date
25/03/2013
Last edited
17/07/2020
Recruitment status
Stopped
Overall study status
Stopped
Condition category
Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

Background and study aims
Acute myeloid leukaemia (AML) is an aggressive cancer of the myeloid cells (a type of white blood cell). Without treatment patients die within a short time after diagnosis. Treatment involves intensive chemotherapy to kill the cancerous cells in the blood and bone marrow. During the chemotherapy different drugs are given in cycles of treatment: treatment for a few days and then a rest period. The number of cycles of treatment depends on the treatment plan and how well the treatment works. The aim of this study is to find out whether adding a new drug called clofarabine improves survival in children and adolescents with AML.

Who can participate?
Patients aged under 18 with newly diagnosed AML

What does the study involve?
The chemotherapy is divided into induction, consolidation and maintenance therapy. The induction treatment aims to get rid of AML, so that there are no leukemia cells in the blood or bone marrow. Participants are randomly allocated to one of two groups. One group is treated with clofarabine in combination with cytarabine and liposomal daunorubicin as induction therapy. The other group is treated with the standard induction therapy of liposomal daunorubicin, cytarabine and etoposide. Most of the drugs are given into a vein, directly into the bloodstream. Sometimes a long tube called central line that helps to give the drugs directly into a large vein in the chest is needed. The second phase of treatment is called consolidation and can be given as courses with chemotherapy drugs similar to induction treatment. The last is maintenance therapy, which is given to stop the cancer coming back. Participants are randomly allocated to be treated with either 1 year or 8 weeks of maintenance therapy using Cytarabin und 6-Thioguanin to find out whether treatment side effects can be reduced and quality of life improved without worsening their chance of survival (prognosis).

What are the possible benefits and risks of participating?
The possible benefits are improved survival through the use of clofarabine in induction therapy and reduction of treatment toxicity and improvement in quality of life by shortening the maintenance therapy without worsening the prognosis. As chemotherapy for AML is one of the most aggressive treatments severe toxic side effects are possible. Some of them can be life threatening, particularly infections. There are different methods to reduce the side effects, for example antibiotics and blood transfusions. Because of the high risk of illness and death the treatment is carried out by experienced professionals.

Where is the study run from?
The study has been set by the Hannover Medical School (Germany) in collaboration with other big national and international hemato/oncology centers from Germany, Austria, Czech Republic, Slovakia and Switzerland

When is the study starting and how long is it expected to run for?
July 2013 to June 2018

Who is funding the study?
German Cancer Aid

Who is the main contact?
Prof. Dr Dirk Reinhardt, dirk.reinhardt@uk-essen.de

Study website

Contact information

Prof Dirk Reinhardt
Scientific

Universitätsklinikum Essen
Hufelandstr. 55
Essen
45147
Germany

Phone +49 (0)201 723 3784
Email dirk.reinhardt@uk-essen.de

Study information

Study designOpen prospective randomized phase III trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details to request a patient information sheet
Scientific titleAML-BFM 2012: clinical trial for the treatment of acute myeloid leukemia in children and adolescents - an open prospective randomized phase III trial
Study acronymAML-BFM 2012
Study objectives1. Improvement in the event-free and overall survival of children and adolescents with acute myeloid leukemia (AML) through the introduction of Clofarabine in induction therapy.
2. Minimization of treatment toxicity and improvement in quality of life by shortening the maintenance therapy without worsening the prognosis.
Ethics approval(s)Not provided at time of registration
Health condition(s) or problem(s) studiedPediatric acute myeloid leukemia
InterventionIn total 500 patients will be recruited with study duration of 5 years and estimated 100 patients randomised per year. Randomisation 1: 448 Patients till the end 2017, randomisation 2: 380 Patients till the end 2017.

Randomisation 1
Arm A: CDxA (Clofarabine; 40mg/m2; 5 days)
Arm B: ADxE (Etoposide; 150 mg/m2/d; 3 days)

Randomisation 2:
Arm A: long maintenance therapy, 1 year
[6-Thioguanin 40 mg/ m2; daily
HD_Cytarabine 1g/m2; infusion, day: 1-3, 6x
Cytarabine, 20-40mg/m2, i.th.; day: 1
Cytarabine, Methotraxate, Prednisolone i.th.; day1; week: 5, 7, 9)

Arm B: short maintenance therapy, 8 weeks
(6-Thioguanine: 40 mg/ m2; daily; week: 4-8
Cytarabine: 40mg/m2; day: 1-4, each 4 weeks
Cytarabine, Methotraxate, Prednisolone i.th.; day: 1, 14, 28, 42)

The early treatment response (% blasts before the second treatment block; days 21-28) and treatment response after the second treatment block (% blasts day 42), event-free, disease-free and overall survival and AML toxicity rates will be evaluated.
Intervention typeDrug
Pharmaceutical study type(s)
PhasePhase III
Drug / device / biological / vaccine name(s)lofarabine, Cytarabine, liposomal Daunorubicin, Etoposide, Idarubicine, Methotrexat, Mitoxantrone, Sorafenib, 6-Thioguanin
Primary outcome measure1. Event-Free Survival (EFS) of the randomized patients. The EFS will be calculated from day 0 (date of diagnosis) to the first event (non-response, relapse, second malignancy or death for any reason) or the last follow-up.
2. Disease-Free Survival (DFS). The DFS will be calculated from date of randomization to the first event (relapse, second malignancy or death for any reason) or the last follow-up.
Secondary outcome measures1. Overall survival
2. Detection of molecular relapse
3. Response kinetics for minimal residual disease.
The minimal Rest Disease (MRD) will be monitored at the start of each treatment element in the peripheral blood (PB) and bone marrow samples (BM). In all patients with molecular or cytogenetic markers for MDR (Fusion genes AML1/ETO, CBL/MYH11, MLL/X, OTT/MAL; Mutations: NPM1, FLT3-ITD, WT1, c-kit, GATA1, CEPBα, RAS)
4. Relapse incidence
5. Quality of life through toxicity monitoring
6. Assessment of safety: Serious Adverse Events (SAE), long-term follow-up of late adverse effects
Overall study start date01/07/2013
Completion date30/06/2018
Reason abandoned (if study stopped)Lack of staff/facilities/resources

Eligibility

Participant type(s)Patient
Age groupChild
Lower age limit0 Years
Upper age limit18 Years
SexBoth
Target number of participants448
Key inclusion criteria1. Diagnosis of an AML (It. WHO classification 2008)
2. Ages 0 to 18 years, either sex
3. Informed Consent of the guardians
Key exclusion criteria1. Existing illnesses / syndromes which exclude treatment
2. Patients with trisomy 21 and ML-DS and/or transient myeloproliferative syndrome (referred to TMD-prevention study or the ML-DS 2006 study)
3. Refusal of treatment/missing consent to treatment or protocol
4. Pregnancy/breastfeeding
5. Patients of child-bearing age who decline a pregnancy test
6. Previous-therapy with cytostatic medicines of more than 14 days
Date of first enrolment01/07/2013
Date of final enrolment30/06/2018

Locations

Countries of recruitment

  • Austria
  • Czech Republic
  • Germany
  • Slovakia
  • Switzerland

Study participating centre

Carl-Neuberg-Str. 1
Hannover
30625
Germany

Sponsor information

Medical School of Hannover (MHH) (Germany)
University/education

Carl-Neuberg-str. 1
Hannover
30625
Germany

Website http://www.mh-hannover.de
ROR logo "ROR" https://ror.org/00f2yqf98

Funders

Funder type

Charity

Deutsche Krebshilfe
Private sector organisation / Other non-profit organizations
Alternative name(s)
Stiftung Deutsche Krebshilfe, German Cancer Aid
Location
Germany

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Editorial Notes

17/07/2020: The following changes have been made:
1. The trial has been halted due to the lack of liposomal daunorubicin.
2. The scientific contact details have been changed.
11/04/2017: Plain English summary added.