Clinical trial NCT04044560: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: B-cell Adult Acute Lymphoblastic Leukemia
Stem Cell Leukemia
Minimal Residual Disease
Keywords: acute lymphoblastic leukemia, blinatumomab, minimal residual disease, stem cell transplant
Lead sponsor: University of British Columbia
Sponsor class: OTHER
Collaborators: name: Amgen
First posted: 2019-08-05
Enrollment: 8
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: MRD Response
timeFrame: Following 1st cycle of blinatumomab (each cycle is 28 days)
Secondary outcomes:
measure: Safety and Tolerability
timeFrame: During Blinatumomab treatment, an average of 24 weeks
measure: Survival
timeFrame: Up to 5 years
measure: Incidence of MRD Post HSCT
timeFrame: Up to day +270 following stem cell transplant
measure: Patient Recruitment (Number of Patients Recruited)
timeFrame: Through Study Completion, an average of 2 years
measure: Turnaround time of centralized MRD testing (days)
timeFrame: Through Study Completion, an average of 2 years
measure: Time to delivery of blinatumomab following MRD detection
timeFrame: Through Study Completion, an average of 2 years
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: Vancouver General Hospital - Leukemia/Bone Marrow Transplant Program
state: British Columbia
city: Vancouver
country: Canada
facility: BC Children's Hospital
state: British Columbia
city: Halifax
country: Canada
facility: QEII - Health Sciences Centre
state: Nova Scotia
Study officials:
affiliation: University of British Columbia
name: David Sanford, MD
role: PRINCIPAL_INVESTIGATOR
References: