- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04044560
Blinatumomab for MRD in Pre-B ALL Patients Following Stem Cell Transplant (OZM-097)
February 3, 2022 updated by: David Sanford, University of British Columbia
Blinatumomab for Minimal Residual Disease (MRD) in Pre-B Cell Acute Lymphoblastic Leukemia Patients Following Hematopoietic Cell Transplantation: A Canadian, Multicentre Trial
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.
Study Overview
Status
Terminated
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
8
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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British Columbia
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Vancouver, British Columbia, Canada, V5Z1M9
- Vancouver General Hospital - Leukemia/Bone Marrow Transplant Program
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Vancouver, British Columbia, Canada, V5Z4H4
- BC Children's Hospital
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Nova Scotia
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Halifax, Nova Scotia, Canada, B3H 2Y9
- QEII - Health Sciences Centre
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
1 year and older (ADULT, OLDER_ADULT, CHILD)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SEQUENTIAL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: 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.
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Continuous intravenous infusion
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
MRD Response
Time Frame: Following 1st cycle of blinatumomab (each cycle is 28 days)
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To determine the proportion of patients with MRD response, defined as negative MRD as measured by flow cytometry, after 1 cycle of blinatumomab.
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Following 1st cycle of blinatumomab (each cycle is 28 days)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety and Tolerability
Time Frame: During Blinatumomab treatment, an average of 24 weeks
|
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).
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During Blinatumomab treatment, an average of 24 weeks
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Survival
Time Frame: Up to 5 years
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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.
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Up to 5 years
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Incidence of MRD Post HSCT
Time Frame: Up to day +270 following stem cell transplant
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To determine the proportion of patients developing detectable MRD following HSCT for B-ALL as measured by flow cytometry.
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Up to day +270 following stem cell transplant
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Patient Recruitment (Number of Patients Recruited)
Time Frame: Through Study Completion, an average of 2 years
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Feasibility
|
Through Study Completion, an average of 2 years
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Turnaround time of centralized MRD testing (days)
Time Frame: Through Study Completion, an average of 2 years
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Feasibility
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Through Study Completion, an average of 2 years
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Time to delivery of blinatumomab following MRD detection
Time Frame: Through Study Completion, an average of 2 years
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Feasibility
|
Through Study Completion, an average of 2 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: David Sanford, MD, University of British Columbia
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
September 8, 2020
Primary Completion (ACTUAL)
February 2, 2022
Study Completion (ACTUAL)
February 2, 2022
Study Registration Dates
First Submitted
July 31, 2019
First Submitted That Met QC Criteria
August 1, 2019
First Posted (ACTUAL)
August 5, 2019
Study Record Updates
Last Update Posted (ACTUAL)
February 21, 2022
Last Update Submitted That Met QC Criteria
February 3, 2022
Last Verified
February 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Neoplastic Processes
- Leukemia
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Leukemia, Lymphoid
- Neoplasm, Residual
- Antineoplastic Agents
- Blinatumomab
Other Study ID Numbers
- H19-00893
- CTTC 1902 (OTHER: Sponsor Protocol No.)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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