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

Brief Summary

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

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.

  • Study Type: Interventional
  • Study Design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
  • Study Primary Completion Date: July 2012

Detailed Clinical Trial 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.

Interventions Used in this Clinical Trial

  • Procedure: R-Blocks
  • Procedure: Protocol II-Ida

Arms, Groups and Cohorts in this Clinical Trial

  • Active Comparator: R-Blöcke
    • Blocktherapie
  • Experimental: Prot-II-Ida
    • a

Outcome Measures for this Clinical Trial

Primary Measures

  • Reduction of MRD
    • Time Frame: a
      Safety Issue?: No
  • event-free and overall survival
    • Time Frame: a
      Safety Issue?: Yes
  • the toxicity associated with each treatment strategy
    • Time Frame: a
      Safety Issue?: No

Secondary 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
    • Time Frame: a
      Safety Issue?: No

Criteria for Participation in this Clinical Trial

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).

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: 18 Years

Are Healthy Volunteers Accepted for this Clinical Trial: No

Clinical Trial Investigator Information

  • Lead Sponsor
    • Charite University, Berlin, Germany
  • Collaborator
    • Deutsche Kinderkrebsstiftung
  • Provider of Information About this Clinical Study
    • Principal Investigator: Gunter Henze, Clinic director – Charite University, Berlin, Germany
  • Overall Official(s)
    • Günter Henze, Prof.Dr.med., Principal Investigator, GPOH

Citations Reporting on Results

Taube T, Eckert C, Korner 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. 2004 Jul;28(7):699-706.

Eckert C, Einsiedel HG, Hartmann R, von Stackelberg A, Volpel 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 lymphoblastic leukemic. Haematologica. 2004 Jul;89(7):ECR23.

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 in: Leukemia. 2004 Jun;18(6):1164. Stackelberg Av [corrected to von Stackelberg A].

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):569-70; author reply 570-1. No abstract available.

Source

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http://clinicaltrialsfeeds.org/clinical-trials/show/NCT00114348