This is an open-label phase I study to determine the safety and recommended phase 2 dose (RP2D) of Senza5 CART5 cells in patients with relapsed or refractory CD5 positive nodal T cell NHL. RP2D will be based on the safety, tolerability, pharmacokinetics, and preliminary efficacy of Senza5 CART5 cells. This trial will evaluate up to 5 dose levels using the Bayesian Optimal Interval (BOIN) design enrolling 3 patients in each cohort to assess safety and achieve therapeutic levels so that the RP2D of Senza5 CART5 cells given as a single IV infusion can be determined.
Histologically or cytologically confirmed relapsed or refractory (r/r) CD5-positive nodal peripheral T-cell lymphoma (such as peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS), nodal T-cell lymphomas with T-follicular helper (TFH) phenotype, including follicular T cell lymphoma, angioimmunoblastic lymphoma, or anaplastic large cell lymphoma) or other non-leukemic CD5+ aggressive mature T cell lymphomas (such as enteropathy-associated T cell lymphoma, monomorphic epitheliotropic intestinal T cell lymphoma, transformed mycosis fungoides, primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma, primary cutaneous insert gamma delta symbols lymphoma, or subcutaneous panniculitis like T cell lymphoma).
≥50% expression of CD5 on flow cytometry or IHC on malignant cells on the most recent biopsy
Must have received at least one line of prior systemic therapy for their lymphoma; participants with anaplastic large cell lymphoma (ALCL) must have received prior brentuximab unless there was a contraindication to brentuximab.
Evaluable disease defined by at least one lesion that can be measured in least 1 dimension and measures at least 1.5 cm in its longest dimension by CT or PET scan, or bone/bone marrow involvement, or skin involvement.
Pregnant or lactating (nursing) women.
HIV infection.
Concurrent use of systemic steroids or immunosuppressant medications.
Any uncontrolled active medical disorder that would preclude participation as outlined.
Sequential
Senza5 CART5
DrugThe Senza5 CART5 drug product consists of a dual population of engineered autologous T cells: CD5 knockout (KO)cells and CD5KO-CART5 cells
Determine the recommended phase 2 dose (RP2D) of Senza5 CART5 cells
Measure the occurrence of Dose Limiting Toxicity events of each dose level per arm
Determine the safety of Senza5 CART5 cells
Quantify quantifying the type and frequency of adverse events
Determine the maximum tolerated dose (MTD)
Quantify the safety and tolerability of the highest dose
Determine the manufacturing feasibility of Senza5 CART5
Quantify the number of product release failures and occurrence of dose failures (inability to meet targeted dose)
Determine efficacy of Senza5 CART5
Measure the objective response rate
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Vittoria Biotherapeutics
Lead sponsor
University of Pennsylvania
Collaborator
