Using modified T cells to treat T Cell Non-Hodgkin Lymphoma

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

This study is testing a new treatment using modified T cells to see if it can help people with relapsed or hard-to-treat T cell Non-Hodgkin Lymphoma.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Vittoria Biotherapeutics (industry)
• Drugs / interventions: brentuximab, alemtuzumab, CAR T, chimeric antigen receptor, chemotherapy, radiation
• Locations: 2 sites (New York, New York and 1 other locations)
• Trial ID: NCT06420089 on ClinicalTrials.gov

What this trial studies

This open-label phase I study aims to evaluate the safety and determine the recommended phase 2 dose of Senza5 CART5 cells in patients with relapsed or refractory CD5 positive nodal T cell Non-Hodgkin Lymphoma. The trial will assess up to five dose levels using a Bayesian Optimal Interval design, enrolling three patients in each cohort to monitor safety and efficacy. The goal is to establish a therapeutic dose for a single intravenous infusion of Senza5 CART5 cells based on pharmacokinetics and preliminary efficacy results.

Who should consider this trial

Good fit: Ideal candidates include individuals with relapsed or refractory CD5-positive nodal peripheral T-cell lymphoma who have received at least one prior systemic therapy.

Not a fit: Patients with CD5-negative lymphomas or those who have not received prior systemic therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a novel treatment option for patients with difficult-to-treat T Cell Non-Hodgkin Lymphoma.

How similar studies have performed: Other studies using CAR T-cell therapies have shown promising results, indicating potential success for this novel approach.

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.

Where this trial is running

New York, New York and 1 other locations

• Columbia University Irving Medical Center — New York, New York, United States (RECRUITING)
• University of Pennsylvania - Abramson Caner Center — Philadelphia, Pennsylvania, United States (RECRUITING)

Study contacts

• Study coordinator: Vittoria Biotherapeutics

Conditions: T Cell Non-Hodgkin Lymphoma, T Cell Lymphoma, Lymphoma, CD5KO CART5, Senza5 CART