ALL-REZ BFM 2002: Multi-Center Study for Children With Relapsed Acute Lymphoblastic Leukemia

Phase 4

Completed

• Conditions: Lymphoblastic Leukemia, Acute; Lymphoma, Non-Hodgkin
• Interventions: Procedure: R-Blocks; Procedure: Protocol II-Ida

• Registration Number: NCT00114348
• Lead Sponsor: Charite University, Berlin, Germany

Brief Summary

The protocol ALL-REZ BFM 2002 aims at the optimization of treatment for children with relapsed acute lymphoblastic leukemia. 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 minimal residual disease (MRD), event-free and overall survival, and the toxicity associated with each treatment strategy.

Detailed Description

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.

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.

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.

Study Timeline

• Study Start: 2003-08
• Study First Submitted: 2005-06-14
• Study First Submitted QC: 2005-06-14
• Study First Posted: 2005-06-15
• Primary Completion: 2012-07
• Study Completion: 2012-07
• Status Verified: 2013-02
• Last Update Submitted: 2013-02-01
• Last Update Posted: 2013-02-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 338

Inclusion Criteria

• Up to 18 years of age
• Morphologically confirmed diagnosis of relapsed non-B ALL or non-B non-Hodgkin lymphoma

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 or 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 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 protocol (e.g. malformation syndromes, cardiac malformations, metabolic disorders).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
R-Blöcke	R-Blocks	Blocktherapie
Prot-II-Ida	Protocol II-Ida	a

Primary Outcome Measures

Name	Time	Method
Reduction of MRD	a
event-free and overall survival	a
the toxicity associated with each treatment strategy	a

Secondary Outcome Measures

Name	Time	Method
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	a

Trial Locations

Locations (1)

ALL-REZ Studienzentrale; 🇩🇪 Berlin, Germany