Clinical Trials /

Blinatumomab in Treating Patients With B-cell Acute Lymphoblastic Leukemia With Minimal Residual Disease

NCT02458014

Description:

This phase II trial studies how well blinatumomab works in treating patients with B-cell acute lymphoblastic leukemia whose disease is in remission (causes no symptoms or signs) but is still present in a small number of cells in the body (minimal residual disease). Immunotherapy with monoclonal antibodies, such as blinatumomab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread.

Related Conditions:
  • Acute Lymphoblastic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Blinatumomab in Treating Patients With B-cell Acute Lymphoblastic Leukemia With Minimal Residual Disease
  • Official Title: Phase II Study of Blinatumomab in Patients With B-Cell Lineage Acute Lymphocytic Leukemia With Positive Minimal Residual Disease

Clinical Trial IDs

  • ORG STUDY ID: 2014-0844
  • SECONDARY ID: NCI-2015-01547
  • SECONDARY ID: 2014-0844
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT02458014

Conditions

  • Adult Acute Lymphoblastic Leukemia in Complete Remission
  • B Acute Lymphoblastic Leukemia
  • Minimal Residual Disease
  • Philadelphia Chromosome Positive

Interventions

DrugSynonymsArms
BlinatumomabAnti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody, Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103, Blincyto, MEDI-538, MT-103Treatment (blinatumomab)

Purpose

This phase II trial studies how well blinatumomab works in treating patients with B-cell acute lymphoblastic leukemia whose disease is in remission (causes no symptoms or signs) but is still present in a small number of cells in the body (minimal residual disease). Immunotherapy with monoclonal antibodies, such as blinatumomab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate the clinical efficacy of blinatumomab in patients B-cell acute lymphoblastic
      leukemia in complete morphologic remission with positive minimal residual disease (MRD) in
      terms of relapse-free survival (RFS).

      SECONDARY OBJECTIVES:

      I. To evaluate other efficacy endpoints such as overall survival and MRD negativity rate by
      flow cytometry and/or polymerase chain reaction (PCR) overall and after the first cycle, as
      well as safety of blinatumomab in this setting.

      OUTLINE:

      Patients receive blinatumomab intravenously (IV) continuously on days 1-28. Treatment repeats
      every 6 weeks for up to 5 cycles in the absence of disease progression or unacceptable
      toxicity. Patients who do not proceed with stem cell transplantation may receive blinatumomab
      IV maintenance therapy with one cycle every 3 months for up to 4 cycles. Patients who remain
      in MRD remission for 3 months and then become MRD positive again can be retreated following
      the same treatment plan previously received.

      After completion of study treatment, patients are followed up every 6 months.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (blinatumomab)ExperimentalPatients receive blinatumomab IV continuously on days 1-28. Treatment repeats every 6 weeks for up to 5 courses in the absence of disease progression or unacceptable toxicity. Patients who do not proceed with stem cell transplantation may receive blinatumomab IV maintenance therapy with one cycle every 3 months for up to 4 cycles. Patients who remain in MRD remission for 3 months and then become MRD positive again can be retreated following the same treatment plan previously received.
  • Blinatumomab

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with B-lineage acute lymphocytic leukemia (ALL) in hematologic complete
             remission (CR) with molecular failure (i.e., had never achieved an MRD-negativity
             status before blinatumomab) or had a molecular relapse (i.e., became MRD positive
             after having been MRD negative) starting at any time point after 3 months of frontline
             therapy; molecular disease or minimal residual disease is defined by a value of at
             least of 1 x 10^-4 (0.01%) by multicolor flow cytometry and/or by next generation
             sequencing (NGS)

          -  Patients with B-lineage ALL in hematologic complete remission (CR) with molecular
             failure (i.e., had never achieved an MRD-negativity status before blinatumomab) or had
             a molecular relapse (i.e., became MRD positive after having been MRD negative)
             starting at any time point after 3 months of frontline therapy; molecular disease or
             minimal residual disease is defined by a value of at least of 1 x 10-4 (0.01%) by
             multicolor flow cytometry and/or by next generation sequencing (NGS)

          -  Performance status of 0, 1, or 2

          -  Creatinine clearance >= 30 ml/minute

          -  Bilirubin less than or equal to 3.0 mg/dL

          -  No active or co-existing malignancy with life expectancy less than 12 months

          -  Patients with Philadelphia chromosome positive (Ph+) ALL can be enrolled in CR1 or CR2
             and beyond; a tyrosine kinase inhibitor (TKI) will be added at the discretion of the
             treating physician; MRD for these patients will be defined by PCR of 0.1% and above
             (International Scale)

        Exclusion Criteria:

          -  Pregnant or nursing women

          -  Known to be human immunodeficiency virus positive (HIV+)

          -  Active and uncontrolled disease/infection as judged by the treating physician

          -  Unable or unwilling to sign the consent form

          -  Active central nervous system (CNS) or extramedullary disease

          -  Monoclonal antibodies therapy within 2 weeks before study entry

          -  Radiotherapy and cancer chemotherapy (except for intrathecal prophylaxis and/or
             low-dose maintenance therapy such as vinca alkaloids, mercaptopurine, methotrexate,
             steroids) or any investigational drug within 2 weeks before study entry
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Relapse-free survival (RFS)
Time Frame:From date of treatment start until the date of death or hematologic or extramedullary disease relapse, assessed up to 18 months
Safety Issue:
Description:RFS will be estimated using the method of Kaplan and Meier. Will compute the Bayesian posterior probability. As a secondary analysis, will perform a competing risk analysis treating stem cell transplant as a competing event for RFS. In addition, will assess the RFS in the subgroup of patients with minimal residual disease (MRD) positivity in at least marrow complete remission (CR) 2 beyond, or in the subgroup of patients with and without allogenic stem cell transplant (ASCT), if permitted by the sample size. Landmark analysis may be performed to assess the difference in RFS between patients with or without receiving ASCT, if permitted by the sample size.

Secondary Outcome Measures

Measure:Event-free survival
Time Frame:Up to 18 months
Safety Issue:
Description:Defined as RFS in addition to lack of achievement of negative MRD status after 2 cycles of blinatumomab (events will include death, lack of response after 2 cycles, and loss of response/progression, including MRD recurrence).
Measure:Overall survival (OS)
Time Frame:Up to 18 months
Safety Issue:
Description:OS will be estimated using the method of Kaplan and Meier. Will assess OS in the subgroup of patients with MRD positivity in at least marrow CR 2 beyond; or in the subgroup of patients with and without ASCT, if permitted by the sample size. Landmark analysis may be performed to assess the difference in OS between patients with or without receiving ASCT, if permitted by the sample size.
Measure:MRD negativity rate
Time Frame:Up to 18 months
Safety Issue:
Description:Will be estimated along with the exact 95% confidence interval.
Measure:MRD negativity rate after course 1
Time Frame:Up to 6 weeks
Safety Issue:
Description:Will be estimated along with the exact 95% confidence interval.
Measure:Incidence of toxicity
Time Frame:Up to 18 months
Safety Issue:
Description:All treated patients are included in the safety analysis set. The adverse events will be summarized by organ type, grade and attribution to study treatment.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

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