Clinical trial NCT06420089: CD5-deleted Chimeric Antigen Receptor Cells (Senza5 CART5) for T Cell Non-Hodgkin Lymphoma (NHL)
Official title: CD5-deleted Chimeric Antigen Receptor Cells (Senza5 CART5) to Enhance Immunotherapy Against T Cell Non-Hodgkin Lymphoma (NHL): a First-in-human Phase I Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: T Cell Non-Hodgkin Lymphoma
Keywords: T Cell Lymphoma
Lymphoma
CD5KO CART5
Senza5 CART
Lead sponsor: Vittoria Biotherapeutics
Sponsor class: INDUSTRY
Collaborators: name: University of Pennsylvania
First posted: 2024-05-17
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Open label
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. 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).
2. ≥50% expression of CD5 on flow cytometry or IHC on malignant cells on the most recent biopsy
3. 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.
4. 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.
5. No circulating CD5+ malignant cells identified by peripheral blood flow cytometry must be present.

Exclusion Criteria:

1. Pregnant or lactating (nursing) women.
2. HIV infection.
3. Concurrent use of systemic steroids or immunosuppressant medications.
4. Any uncontrolled active medical disorder that would preclude participation as outlined.
5. History of immunodeficiency.
6. History of prior chimeric antigen receptor therapy (CAR T), autologous or syngeneic HCT \<100 days from transplant at the time of cell infusion or previous allo-HCT.
7. Active and/or systemic inflammatory or autoimmune diseases.
8. Signs or symptoms indicative of active CNS involvement.
9. Known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, and unrelated to lymphoma or previous lymphoma treatment.
10. Clinically apparent arrhythmia, or arrhythmias that are not stable on medical management
11. Current participation in or prior participation in a study of an investigational agent or using an investigational device within 2 weeks of the first dose of treatment.
12. Prior monoclonal antibody therapy within 4 weeks prior to study Day 1
13. Prior use of alemtuzumab
14. Prior chemotherapy targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1
15. Uncontrolled active infection requiring systemic therapy.
16. Circulating CD5+ malignant cells identified by peripheral blood flow cytometry present.
17. Active and/or systemic inflammatory or autoimmune diseases.

Primary outcomes:
measure: Determine the recommended phase 2 dose (RP2D) of Senza5 CART5 cells
timeFrame: 12 months
Secondary outcomes:
measure: Determine the safety of Senza5 CART5 cells
timeFrame: 12 months
measure: Determine the maximum tolerated dose (MTD)
timeFrame: 12 months
measure: Determine the manufacturing feasibility of Senza5 CART5
timeFrame: 12 months
measure: Determine efficacy of Senza5 CART5
timeFrame: 12 months
measure: Determine efficacy of Senza5 CART5
timeFrame: 12 months
measure: Determine efficacy of Senza5 CART5
timeFrame: 12 months
measure: Determine efficacy of Senza5 CART5
timeFrame: 12 months
measure: Determine efficacy of Senza5 CART5
timeFrame: 12 months
measure: Determine efficacy of Senza5 CART5
timeFrame: 12 months
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: University of Pennsylvania - Abramson Caner Center
state: Pennsylvania
Study officials:
References: