Weill Medical College of Cornell University
This is a clinical trial to evaluate the safety of combining CAR T-cell therapy with low-dose total body irradiation (LD-TBI) in patients with previously treated large B-cell lymphoma (LBCL) or multiple myeloma (MM). The investigators' hypothesis is that the combination will make the immune system more active in fighting cancer by increasing the display of antigens and activating pathways that lead to cell death, including death receptors like FAS and TRAIL2. This approach is expected to help the CAR T cells grow and last longer, leading to stronger anti-tumor effects and more cancer cell deaths. Participants will receive LDTBI treatment before their CAR T cell therapy and will be followed up for 2 years.
This is a single-center, open-label, non-randomized, Phase Ib trial evaluating dose escalation of low-dose total body irradiation (LD-TBI) combined with standard-of-care CAR T-cell therapy in patients with relapsed or refractory large B-cell lymphoma (LBCL) or multiple myeloma (MM). The study includes two disease-specific cohorts: Cohort 1 (LBCL) receives commercial CD19-directed CAR T-cell therapy (axicabtagene ciloleucel or lisocabtagene maraleucel), and Cohort 2 (MM) receives commercial BCMA-directed CAR T-cell therapy (ciltacabtagene autoleucel). In CAR T-cell therapy, T-cells are removed…
Inclusion Criteria: For Diffuse Large B-Cell Lymphoma (DLBCL) Cohort: * Diagnosis of DLBCL that is refractory to first-line chemoimmunotherapy, relapses within 12 months of first-line chemoimmunotherapy, relapses after 12 months in a transplant-ineligible patient, or is relapsed/refractory after two or more lines of systemic therapy. Eligible histologies include DLBCL not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL arising from indolent lymphoma (follicular lymphoma, marginal zone lymphoma, or chronic lymphocytic leukemia) * Age ≥18 y…
Lymphodepleting chemotherapy given in combination with fludarabine on Days -5 to -3.
Alternative lymphodepleting chemotherapy given on Days -5 to -4, for participants receiving ciltacabtagene autoleucel.
Lymphodepleting chemotherapy given in combination with cyclophosphamide on Days -5 to -3.
Commercial CD19-directed CAR T-cell therapy administered intravenously on Day 0, at least 4 hours after completion of LD-TBI.
Commercial CD19-directed CAR T-cell therapy administered intravenously on Day 0, at least 4 hours after completion of LD-TBI.
Commercial BCMA-directed CAR T-cell therapy administered intravenously on Day 0, at least 4 hours after completion of LD-TBI.
A single dose of total body irradiation administered on Day 0, at least 4 hours before the start of CAR T-cell infusion. Dose level (0.5 Gy, 1.0 Gy, or 2.0 Gy) is determined by the assigned dose cohort.