Dysautonomia International

A Study of Obecabtagene Autoleucel in People With B-cell Acute Lymphoblastic Leukemia

Purpose

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).

Condition

Acute Lymphoblastic Leukemia

Eligibility

Eligible Ages: Over 40 Years
Eligible 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) - Inotuzumab or blinatumomab with or without chemotherapy - Tyrosine kinase inhibitor plus steroids, chemotherapy, or blinatumomab - Adequate organ function at time of screening A, including: - ALT or AST ≤5x ULN and total bilirubin ≤2 (or ≤3 if history of Gilbert's syndrome or leukemic infiltration of the liver) - Serum creatinine <2.0mg/dL - SaO2 ≥92% on room air - Left ventricular ejection fraction (LVEF) ≥50% within 1 month of screening - ECOG performance status 0-2 - CD19 expression is required at any time since diagnosis. CD19 expression may be detected by immunohistochemistry or by flow cytometry. Patients receiving prior blinatumomab are eligible if there is no documentation of CD19-negative disease after blinatumomab. - CNS1 status must be documented at time of screening by CSF assessment. Patients with prior CNS2 or CNS3 disease must be CNS1 at screening and have no residual CNS deficits or symptoms. - Patients will need to adhere to institutional contraception guidelines for a minimum of 1 year.

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 - Blinatumomab may not be used as bridging therapy following apheresis - Positive test indicating the presence of active infection with the following pathogens: HIV, Hepatitis B (detectable Hep B DNA by PCR or Hep B surface antigen), Hepatitis C (detectable Hep C RNA by PCR), HTLV, Syphilis. The tests required will be agreed upon with the manufacturer to comply with manufacturer's regulatory and manufacturing requirements.

Study Design

Phase: Phase 2
Study Type: Interventional
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Primary Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
Experimental Cohort A	will enroll Philadelphia chromosome negative patients	Drug: Obecabtagene Autoleucel given as infusion
Experimental Cohort B	is an exploratory cohort that will enroll Philadelphia chromosome positive patients	Drug: Obecabtagene Autoleucel given as infusion

Recruiting Locations

Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities)
Basking Ridge 5095409, New Jersey 5101760 07920