A Phase II Trial of Obecabtagene Autoleucel Consolidation in Adult Patients With Acute Lymphoblastic Leukemia in First Complete Remission Without Measurable Residual Disease
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Enrollment
- 40
- Locations
- 7
- Primary Endpoint
- relapse free survival (RFS) (Cohort A)
Overview
Brief Summary
The researchers are doing this study to find out whether obecabtagene autoleucel (obe-cel) is an effective treatment for people with B-cell acute lymphoblastic leukemia (ALL) that is in complete remission (CR, meaning all signs of cancer are gone) with no measurable residual disease (MRD-negative, meaning there are no detectable cancer cells). Participants in this study will have received past treatment for their B-cell ALL, and their disease will be in MRD-negative CR for the first time (first MRD-negative CR).
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 40 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Diagnosis of CD19+ B-cell ALL.
- •Both Ph-negative and Ph-positive are allowed
- •Patients with EMD must have detectable disease in the bone marrow (by flow cytometry or molecular methods) in order to follow MRD.
- •Patients aged ≥ 40 years at time of screening A.
- •Patients aged 30-39 years (at time of Screening A) are allowed in the presence of high-risk comorbidities or poor tolerability of chemotherapy (e.g. history or experienced pancreatitis with therapy, BMI ≥40kg/m2, underlying liver disease precluding safer administration of pediatric inspired regimens, any further combination of documented severe comorbidities that the investigator judges to be incompatible with administering an intensive pediatric or pediatric-inspired standard chemotherapy regimen).
- •In MRD negative CR or CR with incomplete hematologic recovery (CRi) at the time of screening. MRD will be assessed by flow cytometry and/or molecular testing such as ClonoSEQ at the minimum sensitivity of 10-4 from the bone marrow. Patients with MRD \<10\^-4 will be eligible.
- •Patients may receive more than one course of upfront induction and/or consolidation, but must be in MRD- CR/CRi at time of screening, within 4 months from initiation of treatment. The 4-month window will be measured from the first day of anti-leukemic therapy initiation (excluding steroid prophase) until the Screening A test for the trial.
- •Frontline regimens include but are not limited to:
- •HyperCVAD or mini-hyper-CVD
- •Asparaginase-containing multiagent chemotherapy (e.g. CALGB10403, pediatric inspired chemo)
Exclusion Criteria
- •Concurrent active malignancy excluding non-melanoma skin cancer. Patients with a history of prior malignancy who have been treated with curative intent and have been in remission for at least 2 years are eligible.
- •Burkitt's leukemia or lymphoma
- •Patients with measurable extramedullary disease at screening are excluded. Patients with prior history of extramedullary disease are allowed after documentation of disease resolution by either PET/CT scan (or CT with contrast if PET cannot be performed).
- •The following medications are excluded:
- •Steroids: Therapeutic doses of corticosteroids (greater than 10mg daily of prednisone or its equivalent) within 7 days of leukapheresis or 72 hours prior to CAR T cell infusion.
- •Systemic chemotherapy: Must be discontinued 7 days prior to leukapheresis or 7 days prior to starting lymphodepleting chemotherapy if used during bridging.
- •Tyrosine kinase inhibitors: Must be discontinued 48 hours prior to apheresis and 48 hours prior to starting lymphodepleting chemotherapy, if used during bridging.
- •Blinatumomab must be discontinued 5 days before apheresis
- •Inotuzumab must be discontinued 2 weeks before apheresis to allow T cell recovery
- •Patients with uncontrolled systemic fungal, bacterial, viral or other infection at time of leukapheresis or at time of CAR T cell infusion
Arms & Interventions
Cohort A
will enroll Philadelphia chromosome negative patients
Intervention: Obecabtagene Autoleucel (Drug)
Cohort B
is an exploratory cohort that will enroll Philadelphia chromosome positive patients
Intervention: Obecabtagene Autoleucel (Drug)
Outcomes
Primary Outcomes
relapse free survival (RFS) (Cohort A)
Time Frame: 1 year from infusion
The time from CAR T infusion until non-response, relapse, or death of any cause, censored at last follow up. Non-response will be defined as the presence of \> 5% abnormal lymphoblasts in the bone marrow, or the presence of unequivocal CNS or extramedullary disease after obe-cel infusion. Relapse will be defined as the emergence of \> 5% abnormal lymphoblasts in the bone marrow, or the emergence of new unequivocal CNS or extramedullary disease after obe-cel infusion. Patients will be censored for relapse free survival if they undergo allogenic stem cell transplant or receive any other new treatment (except start or change of TKI maintenance) while in remission.
Secondary Outcomes
- Minimal residual disease (MRD)-negative Event Free Survival (EFS) (Cohort A & B)(1 year from infusion)