Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Blinatumomab for MRD in Pre-B ALL Patients Following Stem Cell Transplant (OZM-097)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04044560
Recruitment Status : Not yet recruiting
First Posted : August 5, 2019
Last Update Posted : August 5, 2019
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
David Sanford, University of British Columbia

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.

Condition or disease Intervention/treatment Phase
B-cell Adult Acute Lymphoblastic Leukemia Stem Cell Leukemia Minimal Residual Disease Biological: blinatumomab Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Sequential Assignment
Intervention Model Description: Participants will be monitored for MRD post transplant during the testing phase of the trial. If they have detectable MRD, they will be enrolled into the blinatumomab treatment phase.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Blinatumomab for Minimal Residual Disease (MRD) in Pre-B Cell Acute Lymphoblastic Leukemia Patients Following Hematopoietic Cell Transplantation: A Canadian, Multicentre Trial
Estimated Study Start Date : September 2019
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : September 2026


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.
Biological: blinatumomab
Continuous intravenous infusion




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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).

  2. 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.

  3. 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.

  4. Patient Recruitment (Number of Patients Recruited) [ Time Frame: Through Study Completion, an average of 2 years ]
    Feasibility

  5. Turnaround time of centralized MRD testing (days) [ Time Frame: Through Study Completion, an average of 2 years ]
    Feasibility

  6. Time to delivery of blinatumomab following MRD detection [ Time Frame: Through Study Completion, an average of 2 years ]
    Feasibility



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   1 Year and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04044560


Contacts
Layout table for location contacts
Contact: David Sanford, MD 604 875 4863 david.sanford@bccancer.bc.ca

Sponsors and Collaborators
University of British Columbia
Amgen
Investigators
Layout table for investigator information
Principal Investigator: David Sanford, MD University of British Columbia

Layout table for additonal information
Responsible Party: David Sanford, Clinical Assistant Professor, University of British Columbia
ClinicalTrials.gov Identifier: NCT04044560     History of Changes
Other Study ID Numbers: H19-00893
CTTC 1902 ( Other Identifier: Sponsor Protocol No. )
First Posted: August 5, 2019    Key Record Dates
Last Update Posted: August 5, 2019
Last Verified: August 2019

Layout table for additional information
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
Keywords provided by David Sanford, University of British Columbia:
acute lymphoblastic leukemia, blinatumomab, minimal residual disease, stem cell transplant
Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasm, Residual
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplastic Processes
Pathologic Processes
Blinatumomab
Antibodies, Bispecific
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs