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

Lymphoma, Non-Hodgkin Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00114348
• Other study ID #: A2002/6a
• Status: Completed
• Phase: Phase 4
• First received: June 14, 2005
• Last updated: February 1, 2013
• Start date: August 2003
• Est. completion date: July 2012

Study information

• Verified date: February 2013
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ethics Commission
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 338
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 18 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Lymphoblastic Leukemia, Acute
• Lymphoma, Non-Hodgkin
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Procedure:
• R-Blocks

• Protocol II-Ida

Locations

Country	Name	City	State
Germany	ALL-REZ Studienzentrale	Berlin

Sponsors (2)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany	Deutsche Kinderkrebsstiftung

Country where clinical trial is conducted

Germany, 

References & Publications (4)

Eckert C, Einsiedel HG, Hartmann R, von Stackelberg A, Völpel S, Guggemos A, Hanzsch N, Kawan L, Seeger K, Henze G. Clonal stability of initial leukemia in a child with central nervous system relapse 7.4 years after bone marrow relapse of common acute lym — View Citation

Herold R, von Stackelberg A, Hartmann R, Eisenreich B, Henze G. Acute lymphoblastic leukemia-relapse study of the Berlin-Frankfurt-Munster Group (ALL-REZ BFM) experience: early treatment intensity makes the difference. J Clin Oncol. 2004 Feb 1;22(3):569-7 — View Citation

Taube T, Eckert C, Körner G, Henze G, Seeger K. Real-time quantification of TEL-AML1 fusion transcripts for MRD detection in relapsed childhood acute lymphoblastic leukaemia. Comparison with antigen receptor-based MRD quantification methods. Leuk Res. 200 — View Citation

Wellmann S, Guschmann M, Griethe W, Eckert C, von Stackelberg A, Lottaz C, Moderegger E, Einsiedel HG, Eckardt KU, Henze G, Seeger K. Activation of the HIF pathway in childhood ALL, prognostic implications of VEGF. Leukemia. 2004 May;18(5):926-33. Erratum — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reduction of MRD		a	No
Primary	event-free and overall survival		a	Yes
Primary	the toxicity associated with each treatment strategy		a	No
Secondary	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	No

External Links

•   ALL-REZ BFM 2002