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

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
8

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z1M9
        • Vancouver General Hospital - Leukemia/Bone Marrow Transplant Program
      • Vancouver, British Columbia, Canada, V5Z4H4
        • BC Children's Hospital
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H 2Y9
        • QEII - Health Sciences Centre

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.
Biological: blinatumomab
Continuous intravenous infusion

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
MRD Response
Time Frame: Following 1st cycle of blinatumomab (each cycle is 28 days)
To determine the proportion of patients with MRD response, defined as negative MRD as measured by flow cytometry, after 1 cycle of blinatumomab.
Following 1st cycle of blinatumomab (each cycle is 28 days)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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).
During Blinatumomab treatment, an average of 24 weeks
Survival
Time Frame: Up to 5 years
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.
Up to 5 years
Incidence of MRD Post HSCT
Time Frame: Up to day +270 following stem cell transplant
To determine the proportion of patients developing detectable MRD following HSCT for B-ALL as measured by flow cytometry.
Up to day +270 following stem cell transplant
Patient Recruitment (Number of Patients Recruited)
Time Frame: Through Study Completion, an average of 2 years
Feasibility
Through Study Completion, an average of 2 years
Turnaround time of centralized MRD testing (days)
Time Frame: Through Study Completion, an average of 2 years
Feasibility
Through Study Completion, an average of 2 years
Time to delivery of blinatumomab following MRD detection
Time Frame: Through Study Completion, an average of 2 years
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of British Columbia

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Amgen

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 8, 2020

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 2, 2022

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 2, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 31, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 1, 2019

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 5, 2019

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 21, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 3, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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