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.
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
Drug | Synonyms | Arms |
---|
blinatumomab | | Blinatumomab 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
Name | Type | Description | Interventions |
---|
Blinatumomab Treatment | Experimental | 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. | |
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: | Recruiting |
Lead Sponsor: | University of British Columbia |
Trial Keywords
- acute lymphoblastic leukemia, blinatumomab, minimal residual disease, stem cell transplant
Last Updated
April 28, 2021