Clinical Trials /

Blinatumomab Bridging Therapy

NCT04556084

Description:

The investigator is testing the ability of a biologically active therapy in blinatumomab, an anti-CD19/CD3 bispecific T-cell engager, to further reduce residual leukemia immediately prior to HCT to improve post-HCT outcomes.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Blinatumomab Bridging Therapy
  • Official Title: Blinatumomab Bridging Therapy in High-Risk B-Acute Lymphoblastic Leukemia: A Phase 2 Study

Clinical Trial IDs

  • ORG STUDY ID: Blina Part 1
  • NCT ID: NCT04556084

Conditions

  • B-cell Acute Lymphoblastic Leukemia
  • Refractory B Acute Lymphoblastic Leukemia
  • Relapsed B-cell Acute Lymphoblastic Leukemia

Interventions

DrugSynonymsArms
BlinatumomabBlinatumomab

Purpose

The investigator is testing the ability of a biologically active therapy in blinatumomab, an anti-CD19/CD3 bispecific T-cell engager, to further reduce residual leukemia immediately prior to HCT to improve post-HCT outcomes.

Detailed Description

      The investigator is testing the ability of a biologically active therapy in blinatumomab, an
      anti-CD19/CD3 bispecific T-cell engager, to further reduce residual leukemia immediately
      prior to HCT to improve post-HCT outcomes. This Phase 2 study will determine the
      effectiveness of delivering 1 to 2 cycles of blinatumomab (Days 1-28) as bridging therapy in
      children, adolescent and young adults with relapse or persistent MRD B-ALL. Eligible subjects
      will receive 1 or 2, 28-day cycles of blinatumomab prior to proceeding to HCT. Centralized
      MRD assessment will be performed after completion of the 28-days of blinatumomab using both
      flow cytometry (University of Washington, Brent Wood, MD) and High-Throughput Deep Sequencing
      (HTS) MRD technologies (Adaptive Technologies, Seattle, WA). Subjects who achieve flow
      cytometry negative MRD (<0.01%) after a single cycle of blinatumomab can proceed directly to
      HCT whereas subjects who remain MRD positive by flow cytometry may receive a 2nd cycle of
      blinatumomab. Subjects who remain MRD positive by flow cytometry after a 2nd cycle of
      blinatumomab will come off study.
    

Trial Arms

NameTypeDescriptionInterventions
BlinatumomabExperimentalUp to 2 cycles of continuous infusion blinatumomab will be given based on the end of Cycle 1 disease response. Cycle 2 of blinatumomab can be given to subjects who have achieved remission (< 5% marrow blasts) after Cycle 1 but have persistent disease identified by multi-parameter flow cytometry (minimal residual disease (MRD) positive ≥ 0.01%) after Cycle 1.
  • Blinatumomab

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnosis of B-ALL in hematologic complete remission (defined as an M1 marrow, < 5%
             blasts) with MRD in the bone marrow (≥ 0.01%) by multi-parameter flow cytometry and
             that meets one of the following:

               -  Patients in first relapse or greater;

        OR

        • Patients with very-high risk biology ALL that is proceeding to HCT in first remission
        (e.g. Induction failure, Severe-hypodiploidy, Ph-like ALL);

        OR

        • Patients who have persistent MRD after Consolidation therapy (End of Consolidation (EOC)
        MRD positive ≥ 0.01%);

        AND with the intent of going on to an allogeneic hematopoietic cell transplantation (HCT)
        independent of this study

          -  Patients must have an available donor and have intention of proceeding directly to HCT
             after completion of 1 to 2 cycles of Bridging therapy with blinatumomab.

          -  Age ≤ 25 years at time of study enrollment

          -  Karnofsky Performance Status ≥ 50% for patients 16 years and older and Lansky Play
             Score ≥ 50 for patients under 16 years of age (see Appendix 1)

          -  Have acceptable organ function as defined within 7 days of study registration:

        Renal: creatinine clearance ≥ 60 mL/min/1.73m2 or serum creatinine based on age/gender

        Hepatic: ALT < 5 x upper limit of normal (ULN) and total bilirubin ≤ 1.5 x upper limit of
        normal (ULN) for age

        Cardiac: left ventricular ejection fraction ≥ 40% by ECHO/MUGA

          -  At least 7 days must have elapsed from prior chemotherapy.

          -  Patients who have experienced their relapse after HCT are eligible, provided they have
             no evidence of acute or chronic Graft-versus-Host Disease (GVHD) and are off all
             transplant immune suppression therapy for at least 7-days (e.g. steroids,
             cyclosporine, tacrolimus). Steroid therapy for non-GVHD and/or non-leukemia therapy is
             acceptable.

          -  Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic
             agent. For agents that have known adverse events occurring beyond 7 days after
             administration, this period must be extended beyond the time during which adverse
             events are known to occur. The duration of this interval must be discussed with the
             study chair.

          -  Monoclonal antibodies: At least 3 half-lives of the antibody must have elapsed after
             the last dose of monoclonal antibody (i.e. Inotuzumab = 12 days).

          -  Immunotherapy: At least 42 days after the completion of any type of immunotherapy
             (e.g. tumor vaccines or CAR T-cell therapy).

          -  XRT: Cranio or craniospinal XRT is prohibited during protocol therapy. ≥ 90 days must
             have elapsed if prior TBI, cranio or craniospinal XRT

          -  Sexually active females of child-bearing potential must agree to use adequate
             contraception (diaphragm, birth control pills, injections, intrauterine device [IUD],
             surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration
             of treatment and for 2 months after the last dose of chemotherapy. Sexually active men
             must agree to use barrier contraceptive for the duration of treatment and for 2 months
             after the last dose of chemotherapy.

          -  Voluntary written consent before performance of any study-related procedure not part
             of normal medical care, with the understanding that consent may be withdrawn by the
             subject at any time without prejudice to future medical care.

        Exclusion Criteria:

          -  History of CNS3 disease and/or active central nervous system (CNS) disease (≥ CNS2)

          -  Receiving concomitant chemotherapy, radiation therapy; immunotherapy or other
             anti-cancer therapy other than is specified in the protocol.

          -  Systemic fungal, bacterial, viral, or other infection not controlled (defined as
             exhibiting ongoing signs/symptoms related to the infection and without improvement,
             despite appropriate antibiotics or other treatment)

          -  Pregnant or lactating. The agents used in this study are known to be teratogenic to a
             fetus and there is no information on the excretion of agents into breast milk. All
             females of childbearing potential must have a blood test or urine study within 7-days
             prior to the start of blinatumomab to rule out pregnancy.

          -  Known allergy to blinatumomab

          -  Participating in a concomitant Phase 1 or 2 study
      
Maximum Eligible Age:25 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Subjects in CR
Time Frame:42 Months
Safety Issue:
Description:The primary efficacy variable is the percent of subjects that remain in Complete Remission (CR) after completion of 1 or 2 cycles of blinatumomab.

Secondary Outcome Measures

Measure:Percentage of Subjects that HTS-MRD Negative
Time Frame:42 Months
Safety Issue:
Description:The percent of subjects that achieve MRD negative by molecular High-Throughput Deep Sequencing (HTS-MRD negative) (MRD undetectable) after completion of 1 to 2 cycles of Blinatumomab.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Michael Burke

Last Updated

September 15, 2020