Author:  Julia Dobke, Last modification: 2014/10/30

ALL-REZ BFM 2002 Protocol for the Treatment of Children with Relapsed Acute Lymphoblastic Leukemia
Disease Relapsed Acute Lymphoblastic Leukemia
Type Prospective, controlled, randomized Treatment Optimization Study
Problem / Objectives

The protocol ALL-REZ BFM 2002 aims at the optimization of treatment for children with relapsed acute lymphoblastic leukemia. It is designed as a prospective controlled randomized multi-center study.
The study is based on the results of five consecutive trials performed by the ALL-REZ BFM study group since 1983. Thus the study meets the criteria of evidence-based therapy, which has been developed over nearly 20 years. Multi-agent chemotherapy in short intensive courses, which are separated by treatment-free intervals, has proved to be a successful form of induction and consolidation therapy. It is followed by preventative (or therapeutic) cranial irradiation and continuation therapy. A number of risk factors, particularly the time of relapse, site of relapse, and the ALL immunophenotype, allow the stratification of patients into a group that has an acceptable prognosis after treatment with chemotherapy alone and a second group that has a high risk of subsequent recurrence following the achievement of a second remission. The latter group requires further intensification of consolidation therapy by allogenic stem cell transplantation (SCT). To date, the indication for SCT has remained unclear for a large and heterogeneous group of patients with an intermediate prognosis. During the precursor study ALL-REZ BFM 96, however, the amount of minimal residual disease (MRD) determined quantitatively with clonal molecular markers after the second induction therapy element was shown to be a highly significant predictor of relapse-free survival.

Main Objectives:

The primary objective of study ALL-REZ BFM 2002 is the randomized comparison of a lower dosed and less intensive, but continuous consolidation therapy with conventional therapy administered in treatment blocks. Outcome measures are the reduction of MRD, event-free and overall survival, and the toxicity associated with each treatment strategy.

Secondary objectives:

The secondary objectives include an improvement of the prognosis in the intermediate risk group using the stratification in treatment arms with and without allogenic SCT based on the MRD result after the second treatment element of induction therapy. An additional aim is to improve the remission induction rate in all groups by increasing the treatment intensity during induction. This is achieved by shortening the intervals between treatment blocks in keeping with the principles of guiding therapy as defined in the protocol. A series of biological companion studies aims to advance our understanding of the disorder and to establish novel prognostic factors that will allow a risk-adapted therapy.

Inclusion Criteria
  • Age: 0-18 yearsRezidiv einer non-B-ALL bzw. non-B-NHL
  • Morphologically confirmed diagnosis of relapsed non-B ALL or non-B non-Hodgkin lymphoma
  • Start of therapy during tretament phase
  • Written informed consens
Exclusion Criteria
  • they have completed the 18th year of life at the time the relapse is diagnosed.
  • curative therapy is declined either by patient himself/herself of the respective legal guardian
  • the patient is pregnant
  • the patient is breast feeding
  • essential parts of the relapse therapy are declined either by the patient or his/her legal guardian or cannot be administered because of medical reasons.
  • no consent is given for transmission of data
  • the patient has a severe concomitant disease that does not allow treatment according to the protocol (e.g. malformation syndromes, cardiac malformations, metabolic disorders
Recruitment 450
Status 01.08.2003 - 31.12.2011 (End of treatment phase); 31.08.2015 End of trial)
Entry Study Register NCT00114348
Principal Investigator Prof. Dr. Dr. h.c. Günter Henze


PD Dr. med. Arend von Stackelberg Charité, Campus Virchow-Klinikum Klinik f. Pädiatrie m. S. Onkologie und Hämatologie Augustenburger Platz 1 13353 Berlin Telefon +49 (30) 450 566833 Fax +49 (30) 450 566901


Andrea Kretschmann Charité, Campus Virchow-Klinikum ALL-REZ Studienzentrale, Klinik für Pädiatrie m.S.Onkologie und Hämatologie Augustenburger Platz 1 13353 Berlin Telefon +49 (30) 450 566 354 Fax +49 (30) 450 566 901


Participants Germany, Austria, Switzerland, Prag, Toronto
Sponsoring The ALL-REZ BFM 2002 trial is supported by the Deutsche Kinderkrebsstiftung