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

NCT ID: NCT04044560

Last Updated: 2022-02-21

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-08
• Study Completion Date: 2022-02-02

Brief Summary

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Blinatumomab Treatment

Eligible 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.

Group Type: EXPERIMENTAL

blinatumomab

Intervention Type: BIOLOGICAL

Continuous intravenous infusion

Interventions

blinatumomab

Continuous intravenous infusion

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

• 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

• 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:

• 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.

• Minimum Eligible Age: 1 Year
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: collaborator

University of British Columbia

OTHER

Sponsor Role: lead

Responsible Party

David Sanford

Clinical Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

David Sanford, MD

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia

Locations

Vancouver General Hospital - Leukemia/Bone Marrow Transplant Program

Vancouver, British Columbia, Canada

BC Children's Hospital

Vancouver, British Columbia, Canada

QEII - Health Sciences Centre

Halifax, Nova Scotia, Canada

Countries

Canada

Other Identifiers

CTTC 1902

Identifier Type: OTHER

Identifier Source: secondary_id

H19-00893

Identifier Type: -

Identifier Source: org_study_id