This is a non-randomized clinical trial to evaluate the safety and efficacy of CD22CART administered after lymphodepleting chemotherapy in adults with relapsed / refractory B Cell Lymphomas. All evaluable participants will be followed for overall survival (OS), progression free survival (PFS), and duration of response (DOR). An evaluable participant is one who completes leukapheresis, lymphodepleting chemotherapy and CART infusion.
Relapsed or refractory disease after at least 2 lines of systemic therapy. Prior therapy must have included an anti-CD20 monoclonal antibody combined with systemic therapy (single-agent anti- CD20 antibody does not count as line of therapy for eligibility nor does local radiation). Anti-CD20 antibody is not required for participants with CD20 negative disease. A systemic therapy includes, but is not limited to: Bendamustine, CHOP, CVP, CART therapy, lenalidomide, or platinum-based chemotherapy.
Relapsed or progressive disease within 24 months of initiation of the initial course of chemotherapy (also known as progression of disease within 24 months POD24). Initial treatment must have included an anti-CD20 monoclonal antibody (unless CD20 negative) plus either Bendamustine, CHOP or CVP (R-Chemo). Must have completed 3 or more cycles of R-Chemo. Progression is measured from the initial day of treatment of the first cycle of R-Chemo. In the case of those who received anti-CD20 monoclonal antibody monotherapy previously and then received R-Chemo are also eligible if they are POD24, and progression is measured from the initial day of treatment of the first cycle of R-Chemo and not from the initial day of anti-CD20 monoclonal antibody monotherapy.
Diagnosis of HCL and require treatment as defined by having HCL-related anemia (hemoglobin <11 g/dL), thrombocytopenia (platelets<100 x 10^9 /L), or neutropenia (absolute neutrophil count below 1.5 x 10^9/L); symptomatic splenomegaly or adenopathy; or other constitutional symptoms directly related to HCL;
Must have progressed or been refractory to 2 lines of therapy including a purine nucleoside analog.
Presence rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy.
Parallel
CD22CART Infusion
DrugDosing and Administration Participants will be hospitalized to receive treatment with CD22CART, if not previously hospitalized, and will remain hospitalized for approximately 5 to 7 (±2) days. Patients may be discharged once all AEs have resolved to Grade 1 or better, or at the discretion of the treating physician. Participants may be discharged with non critical and clinically stable or slowly improving toxicities (e.g., renal insufficiency, cytopenias) even if \> Grade 1, if deemed appropriate by the investigator.
Determine the manufacturing feasibility of CD22 CART by assessing the target dose level and release specifications in each disease cohort.
Rate of successful manufacture of CD22CART cells at the target dose level that meet required release specifications in Cohort 1, Cohort 2, and Cohort 3.
Maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D)
Establish the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of CD22CART cells in 3 cohorts of adults with relapsed/refractory B Cell lymphoma.
Determine the overall response rate (ORR) in adults with follicular lymphoma (FL) and mantle cell lymphoma (MCL)
Assess the ORR at 3 months post CD22 CART infusion as defined by the disease specific response criteria for Cohort 1 (FL) and Cohort 2 (MCL)
Evaluate Progression Free Survival (PFS)
Evaluate Progression Free Survival (PFS) in adults with relapsed/refractory B cell lymphoma after receiving CD22CART. PFS defined as the interval from CD22CART infusion to time of disease progression or death from any cause
Evaluate Overall Survival (OS)
Evaluate Overall Survival (OS) in adults with relapsed/refractory B cell lymphoma after receiving CD22CART. OS defined as the interval from CD22CART infusion to the time of death from any cause.
Evaluate Duration of Response (DOR)
Evaluate Duration of Response (DOR) in adults with relapsed/refractory B cell lymphoma after receiving CD22CART. DOR defined as the interval from achieving an objective response to the time of disease progression.
Assess the response rate in adults with relapsed/refractory Hairy cell leukemia (HCL), Lymphoplasmacytic lymphoma (Waldenstrom macroglobulemia) (WM), Burkitt lymphoma (BL), and Marginal Zone lymphoma (MZL).
Describe the response rates assessed at 3 months post CD22 CART infusion for Cohort 3 (HCL, WM, BL, and MZL).
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Stanford University
Lead sponsor
The Leukemia and Lymphoma Society
Collaborator
