Clinical Trials /

International Study for Treatment of High Risk Childhood Relapsed ALL 2010

NCT03590171

Description:

The main goal of this study is to improve the outcome of children and adolescents with acute lymphoblastic leukemia with high risk first relapse by optimization of treatment strategies within a large international trial and the integration of new agents.

Related Conditions:
  • Acute Lymphoblastic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: International Study for Treatment of High Risk Childhood Relapsed ALL 2010
  • Official Title: International Study for Treatment of High Risk Childhood Relapsed ALL 2010 A Randomized Phase II Study Conducted by the Resistant Disease Committee of the International Berlin, Frankfurt, Münster (BFM) Study Group

Clinical Trial IDs

  • ORG STUDY ID: IntReALL HR 2010
  • NCT ID: NCT03590171

Conditions

  • Acute Lymphoblastic Leukemia (ALL)

Interventions

DrugSynonymsArms
BortezomibArm HR-B

Purpose

The main goal of this study is to improve the outcome of children and adolescents with acute lymphoblastic leukemia with high risk first relapse by optimization of treatment strategies within a large international trial and the integration of new agents.

Detailed Description

      Though survival of children with acute lymphoblastic leukemia (ALL) has considerably improved
      over the past few decades, relapsed ALL remains a leading cause of mortality in children with
      cancer. Risk has been defined by the International (I) Berlin, Frankfurt, Münster (BFM) Study
      Group (SG) based on duration of first remission, immunophenotype of malignant clone, and site
      of relapse. Patients classified as high risk (HR) by these criteria have poor response rates
      to standard induction therapy, high rates of subsequent relapse and require an allogeneic
      hematopoetic stem cell transplantation (allo-HSCT) for consolidation of 2nd remission. Over
      the last decade members of the I-BFM-SG have investigated the use of different combinations
      of conventional cytotoxic agents. Even with allo-HSCT, none of these approaches have improved
      outcome above 40%. Therefore, for HR patients there is a need to investigate the curative
      potential of new agents combined with systemic therapy. The proteasome inhibitor bortezomib
      has shown synergistic activity with acceptable toxicity when combined with corticosteroids,
      anthracyclines and alkylating agents in adult patients with cancer as well as with
      dexamethasone, doxorubicin, vincristine and polyethylene glycol (PEG) asparaginase in
      children with refractory or relapsed ALL. In the I-BFM-SG International Study for Treatment
      of High Risk Childhood Relapsed ALL (IntReALL) HR 2010 study, the potential of Bortezomib
      combined with a modified ALL relapse protocol 3 (R3) backbone as induction regimen for HR
      patients to improve complete 2nd remission (CR2) rates will be investigated in a randomized
      phase II design. Induction is followed by conventional intensive consolidation. After
      termination of the trial patients may be subjected to an investigational window, before all
      of them receive allo-HSCT.
    

Trial Arms

NameTypeDescriptionInterventions
Arm HR-ANo InterventionInduction: Backbone ALL R3
    Arm HR-BExperimentalInduction: Backbone ALL R3 + Bortezomib
    • Bortezomib

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Morphologically confirmed diagnosis of 1st relapsed precursor B-cell or T-cell ALL
    
              -  Children less than 18 years of age at date of inclusion into the study
    
              -  Meeting HR criteria any BM relapse, early/very early isolated BM relapse, very early
                 isolated/combined extramedullary relapse)
    
              -  Patient enrolled in a participating centre
    
              -  Written informed consent
    
              -  Start of treatment falling into the study period
    
              -  No participation in other clinical trials 30 day prior to study enrolment that
                 interfere with this protocol, except trials for primary ALL
    
            Exclusion Criteria:
    
              -  BCR-ABL/ t(9;22) positive ALL
    
              -  Pregnancy or positive pregnancy test (urine sample positive for β-humane
                 choriongonadotropin (HCG) > 10 U/l)
    
              -  Sexually active adolescents not willing to use highly effective contraceptive method
                 (pearl index <1) until 12 months after end of anti-leukemic therapy
    
              -  Breast feeding
    
              -  Relapse post allogeneic stem-cell transplantation
    
              -  Neuropathy > II°
    
              -  The whole protocol or essential parts are declined either by patient himself/herself
                 or the respective legal guardian
    
              -  Objection to the study participation by a minor patient, able to object
    
              -  Any patient being dependent on the investigator
    
              -  No consent is given for saving and propagation of pseudonymized medical data for study
                 reasons
    
              -  Severe concomitant disease that does not allow treatment according to the protocol at
                 the investigator's discretion (e.g. malformation syndromes, cardiac malformations,
                 metabolic disorders)
    
              -  Subjects unwilling or unable to comply with the study procedures
    
              -  Subjects who are legally detained in an official institute
          
    Maximum Eligible Age:17 Years
    Minimum Eligible Age:N/A
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Rate of Complete Remission
    Time Frame:Week 4
    Safety Issue:
    Description:Rate of complete second remission (CR2) quantified by cytology after induction with standard chemotherapy + bortezomib (arm B) compared with standard chemotherapy (arm A).

    Secondary Outcome Measures

    Measure:Event-free Survival
    Time Frame:Year 3
    Safety Issue:
    Description:Improvement of three years event-free survival (EFS)
    Measure:Overall Survival
    Time Frame:Year 3
    Safety Issue:
    Description:Improvement of three years overall survival (OS)
    Measure:Minimal Residual Disease Reduction (MRD)
    Time Frame:Week 4
    Safety Issue:
    Description:Improvement of Minimal Residual Disease (MRD) reduction after induction with versus without bortezomib
    Measure:Minimal Residual Disease Load
    Time Frame:Week 15
    Safety Issue:
    Description:Improvement of MRD load prior to stem cell transplantation (SCT).
    Measure:Minimal Residual Disease (MRD)
    Time Frame:Week 15
    Safety Issue:
    Description:Prognostic relevance of MRD pre stem cell transplantation (SCT). MRD will be quantified before stem cell transplantation with polymerase chain reaction (PCR) and will be related to EFS after SCT. Multicolour flow cytometry will be used in parallel with PCR. Flow cytometry is used instead of PCR if PCR based MRD-quantification cannot be performed, because criteria for a reliable and reproducible sensitive quantification are not fulfilled.
    Measure:Complete Remission/Minimal Residual Disease Rates During Consolidation
    Time Frame:Week 5, 8, 11, 15
    Safety Issue:
    Description:Improvement of CR2 and/or MRD rates during consolidation
    Measure:Toxicity of induction classified with the COMMON TOXICITY CRITERIA (CTC)
    Time Frame:At induction up to week 5
    Safety Issue:
    Description:Toxicity of induction with versus without bortezomib. Toxicity of the central nervous system and peripheral neuropathy will be classified with the COMMON TOXICITY CRITERIA (CTC).

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Charite University, Berlin, Germany

    Trial Keywords

    • ALL

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