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

Sponsor

Charite University, Berlin, Germany (Other)

Overall Status

Completed

CT.gov ID

NCT00114348

Collaborator

Deutsche Kinderkrebsstiftung (Other)

338

Enrollment

Location

Arms

107

Duration (Months)

3.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoblastic Leukemia, Acute Lymphoma, Non-Hodgkin	Procedure: R-Blocks Procedure: Protocol II-Ida	Phase 4

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 Design

Study Type:

Interventional

Actual Enrollment :

338 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

ALL-REZ BFM 2002: Protocol for the Treatment of Children With Relapsed Acute Lymphoblastic Leukemia

Study Start Date :

Aug 1, 2003

Actual Primary Completion Date :

Jul 1, 2012

Actual Study Completion Date :

Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: R-Blöcke Blocktherapie	Procedure: R-Blocks
Experimental: Prot-II-Ida a	Procedure: Protocol II-Ida

Arm

Intervention/Treatment

Active Comparator: R-Blöcke

Blocktherapie

Procedure: R-Blocks

Experimental: Prot-II-Ida

Procedure: Protocol II-Ida

Outcome Measures

Primary Outcome Measures

Reduction of MRD [a]
event-free and overall survival [a]
the toxicity associated with each treatment strategy [a]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).