Clinical Trials /

Inotuzumab Ozogamicin in Treating Patients With B-cell Acute Lymphocytic Leukemia With Positive Minimal Residual Disease

NCT03441061

Description:

This phase II trial studies how well inotuzumab ozogamicin works in treating patients with B-cell acute lymphocytic leukemia with positive minimal residual disease. Inotuzumab ozogamicin is a monoclonal antibody called inotuzumab linked to a toxic agent called ozogamicin. Inotuzumab ozogamicin attaches to B cell-specific CD22 cancer cells in a targeted way and kills them.

Related Conditions:
  • B-Cell Acute Lymphoblastic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 2015-0921
  • SECONDARY ID: NCI-2018-00936
  • SECONDARY ID: 2015-0921
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT03441061

Conditions

  • Acute Lymphoblastic Leukemia
  • Allogeneic Hematopoietic Stem Cell Transplantation Recipient
  • B Acute Lymphoblastic Leukemia
  • Minimal Residual Disease
  • Philadelphia Chromosome Positive
  • Recurrent B Acute Lymphoblastic Leukemia

Interventions

DrugSynonymsArms
Inotuzumab OzogamicinBesponsa, CMC-544, Way 207294, WAY-207294Treatment (inotuzumab ozogamicin)

Purpose

This phase II trial studies how well inotuzumab ozogamicin works in treating participants with B-cell acute lymphocytic leukemia with positive minimal residual disease. Inotuzumab ozogamicin is a monoclonal antibody called inotuzumab linked to a toxic agent called ozogamicin. Inotuzumab ozogamicin attaches to B cell-specific CD22 cancer cells in a targeted way and kills them.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate the clinical efficacy of inotuzumab ozogamicin in patients B-cell acute
      lymphoblastic leukemia (ALL) 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 inotuzumab ozogamicin in this setting.

      OUTLINE:

      Participants receive inotuzumab ozogamicin intravenously (IV) over 1 hour on days 1, 8, and
      15 of cycle 1 and days 1 and 8 of subsequent cycles. Treatment repeats every 28 days for up
      to 4 cycles in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, participants are followed up at 30 day and then
      periodically every 6 months.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (inotuzumab ozogamicin)ExperimentalParticipants receive inotuzumab ozogamicin IV over 1 hour on days 1, 8, and 15 of cycle 1 and days 1 and 8 of subsequent cycles. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
  • Inotuzumab Ozogamicin

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with B-lineage ALL in hematologic complete remission (CR) with molecular
             failure (i.e., had never achieved an MRD-negativity status before inotuzumab
             ozogamicin) 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
             10^-4 (0.01%) by multicolor flow cytometry, PCR and/or next-generation sequencing
             (NGS).

          -  Patients with B-lineage ALL in at least marrow CR in salvage 1 and beyond with MRD
             failure at any time point after 1 month of salvage therapy are allowed, including
             patients who received prior allogeneic stem cell transplantation.

          -  Patients with Philadelphia chromosome (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 either 1.) a ratio of
             BCR-ABL1 to ABL1 by PCR of 0.01% according to the international scale for patients
             with p210 transcript or a ratio of BCR-ABL1 to ABL1 by PCR of 0.01% for patients with
             non-p210 transcripts, or 2.) detectable MRD at a level of at least 1x10^-4 (0.01%) by
             multicolor flow cytometry and/or by NGS.

          -  Performance status of 0, 1, or 2

          -  Creatinine clearance >= 15 ml/min

          -  Bilirubin < 1.5 X upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 X ULN

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

        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 or 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:Up to 4 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Up to 4 years
Safety Issue:
Description:Will continuously monitor treatment-related toxicities using the Bayesian approach of Thall, Simon, Estey. For the purpose of toxicity monitoring, toxicities are defined as any treatment-related grade 3 or 4 non-hematologic adverse events occurring any time during the trial.
Measure:Overall survival
Time Frame:Up to 4 years
Safety Issue:
Description:
Measure:Minimal residual disease (MRD) negativity rate
Time Frame:Up to 4 years
Safety Issue:
Description:

Details

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

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