Clinical Trials /

Blinatumomab for MRD in Pre-B ALL Patients Following Stem Cell Transplant

NCT04044560

Description:

This is a single arm, open label, multi-centre phase II study using blinatumomab for treatment of detectable minimal residual disease (MRD) in the first year following allogeneic hematopoietic stem cell transplant (HSCT) for patients with B cell acute lymphoblastic leukemia (B-ALL). The study has 2 phases: 1. MRD testing phase and 2. blinatumomab treatment phase. Participants with B-ALL planning for HSCT meeting other eligibility criteria will be enrolled onto the MRD testing phase, which will involve centralized MRD testing of bone marrow aspirate samples on day +56, +100, +180, +270 following HSCT. Participants with detectable MRD ≥10^-4 leukemic cells/total nucleated cells will enroll onto the treatment phase. Blinatumomab treatment will be started following detection of MRD after 7 to 42 days from enrollment onto the treatment phase to allow for initiation of taper of immunosuppressive medications.

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

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Blinatumomab for MRD in Pre-B ALL Patients Following Stem Cell Transplant
  • Official Title: Blinatumomab for Minimal Residual Disease (MRD) in Pre-B Cell Acute Lymphoblastic Leukemia Patients Following Hematopoietic Cell Transplantation: A Canadian, Multicentre Trial

Clinical Trial IDs

  • ORG STUDY ID: H19-00893
  • SECONDARY ID: CTTC 1902
  • NCT ID: NCT04044560

Conditions

  • B-cell Adult Acute Lymphoblastic Leukemia
  • Stem Cell Leukemia
  • Minimal Residual Disease

Interventions

DrugSynonymsArms
blinatumomabBlinatumomab Treatment

Purpose

This is a single arm, open label, multi-centre phase II study using blinatumomab for treatment of detectable minimal residual disease (MRD) in the first year following allogeneic hematopoietic stem cell transplant (HSCT) for patients with B cell acute lymphoblastic leukemia (B-ALL). The study has 2 phases: 1. MRD testing phase and 2. blinatumomab treatment phase. Participants with B-ALL planning for HSCT meeting other eligibility criteria will be enrolled onto the MRD testing phase, which will involve centralized MRD testing of bone marrow aspirate samples on day +56, +100, +180, +270 following HSCT. Participants with detectable MRD ≥10^-4 leukemic cells/total nucleated cells will enroll onto the treatment phase. Blinatumomab treatment will be started following detection of MRD after 7 to 42 days from enrollment onto the treatment phase to allow for initiation of taper of immunosuppressive medications.

Trial Arms

NameTypeDescriptionInterventions
Blinatumomab TreatmentExperimentalEligible patients with detectable MRD will taper immunosuppressive medications, if applicable, and undergo treatment with blinatumomab. The duration of each cycle of blinatumomab treatment is 6 weeks. Adult and pediatric patients will be treated for 4 weeks followed by a 2-week treatment free period. Patients may receive up to 4 cycles total of blinatumomab therapy.
  • blinatumomab

Eligibility Criteria

        Testing Phase of Trial:

        Inclusion Criteria:

          -  Pre-B-ALL in complete remission (CR), <5% blasts on most recent bone marrow aspirate
             determined by morphologic assessment, with an intention to proceed to allogeneic HSCT.
             Eligible participants can be in 1st CR or greater. Presence of detectable MRD by flow
             cytometry or other techniques in patients that are in morphologic remission prior to
             transplant is permitted.

          -  Detectable MRD measured by flow cytometry or other molecular techniques is acceptable
             for enrollment in patients with <5% blasts.

          -  Patients with either Philadelphia chromosome positive or negative B-ALL are eligible

          -  Documented expression of CD19 on the lymphoblast population as measured by
             flow-cytometry if patient has received prior CD19-directed therapy.

          -  Eligibility for HSCT along with conditioning regimen and donor selection will be
             determined according to the treating centre's policy.

          -  Patients must be age ≥1 years and have a baseline performance status of ECOG ≤ 2
             (adult) or Lansky ≥ 50% (pediatric).

          -  Patient with chronic hepatitis B (Hep B surface antigen or Hep B Core antibody
             reactive) are eligible if they are receiving treatment to prevent reactivation (e.g.
             lamivudine, tenofovir) and have undetectable serum Hepatitis B DNA

          -  Patients (or legally acceptable designate) must provide written consent.

          -  Female patients of childbearing potential should be willing to use 2 methods of birth
             control or be surgically sterile, or abstain from heterosexual activity for the course
             of the study from the time of informed consent signature date until 3 months after
             completion of study treatment. Patients of childbearing potential are those who have
             not been surgically sterilized or have not been free from menses for > 1 year.

        Exclusion Criteria:

          -  Inability to comply with study procedures.

          -  Active central nervous system (CNS) involvement or other extramedullary disease at the
             time of enrollment.

          -  Uncontrolled infection until resolved.

          -  Burkitt lymphoma/leukemia or mixed phenotype leukemia.

          -  Chronic infection with Hepatitis C. Previously treated Hepatitis C with undetectable
             Hepatitis C RNA for six months or longer is acceptable.

          -  HIV 1/2 Infection.

        Treatment Phase of Trial:

        Inclusion Criteria:

          -  Detectable MRD ≥ 10^-4 leukemic cells/TNC on a bone marrow aspirate done on day +56,
             +100, +180 or day +270.

          -  Morphologic remission on bone marrow from same date (on day +56, +100, +180 or day
             +270)

          -  Patients must be age ≥1 years and have a baseline performance status of ECOG ≤ 2
             (adult) or Lansky ≥ 50% (pediatric) documented within 7 days of enrollment.

          -  Patients with either Philadelphia chromosome positive or negative B-ALL are eligible

          -  Documented expression of CD19 on the lymphoblast population as measured by
             flow-cytometry if patient has received prior CD19-directed therapy.

          -  Patient with chronic hepatitis B (Hep B surface antigen or Hep B Core antibody
             reactive) are eligible if they are receiving treatment to prevent reactivation (e.g.
             lamivudine, tenofovir) and have undetectable serum Hepatitis B DNA

          -  Adequate organ, liver and renal function including: Total bilirubin ≤ 1.5 x upper
             limit of normal (ULN), eGFR >30 mL/min/1.73 m, Alkaline phosphatase ≤ 2.5 x ULN, Serum
             lipase ≤ 1.5 x ULN

          -  Patients (or legally acceptable designate) must provide written consent.

        Exclusion Criteria:

          -  Active acute GVHD (grade II-IV) or active moderate-severe chronic GVHD (NIH Grade) at
             the time of MRD detection are ineligible treatment phase until GVHD resolves or
             quiescent as determined by the treating physician.

          -  Uncontrolled infection until resolved.

          -  Chronic infection with Hepatitis C. Previously treated Hepatitis C with undetectable
             Hepatitis C RNA for six months or longer is acceptable.

          -  HIV 1/2 Infection.

          -  Extramedullary or CNS disease or the time of MRD detection.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:1 Year
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:MRD Response
Time Frame:Following 1st cycle of blinatumomab (each cycle is 28 days)
Safety Issue:
Description:To determine the proportion of patients with MRD response, defined as negative MRD as measured by flow cytometry, after 1 cycle of blinatumomab.

Secondary Outcome Measures

Measure:Safety and Tolerability
Time Frame:During Blinatumomab treatment, an average of 24 weeks
Safety Issue:
Description:Safety of delivering blinatumomab will be monitored early during the post-transplant course. Safety will be evaluated by the onset of treatment emergent adverse events (TEAEs) and by documentation of the incidence and severity of acute and chronic graft versus host disease (GvHD).
Measure:Survival
Time Frame:Up to 5 years
Safety Issue:
Description:Clinically relevant survival outcomes for patients enrolled onto the study including: 2-year and 5-year overall survival (OS) and event free-survival (EFS) and median OS.
Measure:Incidence of MRD Post HSCT
Time Frame:Up to day +270 following stem cell transplant
Safety Issue:
Description:To determine the proportion of patients developing detectable MRD following HSCT for B-ALL as measured by flow cytometry.
Measure:Patient Recruitment (Number of Patients Recruited)
Time Frame:Through Study Completion, an average of 2 years
Safety Issue:
Description:Feasibility
Measure:Turnaround time of centralized MRD testing (days)
Time Frame:Through Study Completion, an average of 2 years
Safety Issue:
Description:Feasibility
Measure:Time to delivery of blinatumomab following MRD detection
Time Frame:Through Study Completion, an average of 2 years
Safety Issue:
Description:Feasibility

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of British Columbia

Trial Keywords

  • acute lymphoblastic leukemia, blinatumomab, minimal residual disease, stem cell transplant

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