CD5-deleted Chimeric Antigen Receptor Cells (Senza5 CART5) for T Cell Non-Hodgkin Lymphoma (NHL) (VIPER101)

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 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.

Study Overview

• Status: Recruiting
• Conditions: T Cell Non-Hodgkin Lymphoma
• Intervention / Treatment: Drug: Senza5 CART5

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Vittoria Biotherapeutics; Phone Number: (215) 600-1380; Email: ClinOps@vittoriabio.com

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Irving Medical Center
      • Contact: Clinical Protocol and Data Management Office; Phone Number: 212-342-5162; Email: cancerclinicaltrials@cumc.columbia.edu
      • Principal Investigator: Ran Reshef, MD, MSc
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania - Abramson Caner Center
      • Contact: Brittany J Koch - Program Manager, Lymphoma Clinical Research, MPH, CCRP; Phone Number: 215-776-5548; Email: Brittany.Koch@pennmedicine.upenn.edu
      • Contact: Michael McNicholas - Clinical Trial Nurse, MBA, MSN, OCN, RN; Phone Number: 267-804-4081; Email: michael.mcnicholas@pennmedicine.upenn.edu
      • Principal Investigator: Dr. Stefan K Barta - Assoc. Prof. & Leader, T-Cell Lymphoma Program, MD, MS, MRCP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Senza5 CART5 with standard of care lymphodepletion; Four treatment arms with Standard of Care Lymphodepletion: Fludarabine 25mg/m2 IV for 3 days Cyclophosphamide 250mg/m2 IV for 3 days	Drug: Senza5 CART5; The Senza5 CART5 drug product consists of a dual population of engineered autologous T cells: CD5 knockout (KO)cells and CD5KO-CART5 cells
Experimental: Senza5 CART5 without standard of care lymphodepletion; Four treatment arms in patients are lymphopenic into the corresponding dose level.	Drug: Senza5 CART5; The Senza5 CART5 drug product consists of a dual population of engineered autologous T cells: CD5 knockout (KO)cells and CD5KO-CART5 cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the safety of Senza5 CART5 cells	Quantify quantifying the type and frequency of adverse events	12 months
Determine the maximum tolerated dose (MTD)	Quantify the safety and tolerability of the highest dose	12 months
Determine the manufacturing feasibility of Senza5 CART5	Quantify the number of product release failures and occurrence of dose failures (inability to meet targeted dose)	12 months
Determine efficacy of Senza5 CART5	Measure the objective response rate	12 months
Determine efficacy of Senza5 CART5	Measure the complete response rate	12 months
Determine efficacy of Senza5 CART5	Measure the best overall response	12 months
Determine efficacy of Senza5 CART5	Measure the duration of response	12 months
Determine efficacy of Senza5 CART5	Measure the overall survival	12 months
Determine efficacy of Senza5 CART5	Measure the progression free survival	12 months

Collaborators and Investigators

• Sponsor: Vittoria Biotherapeutics
• Collaborators: University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2024
• Primary Completion (Estimated): August 30, 2028
• Study Completion (Estimated): August 30, 2029

Study Registration Dates

• First Submitted: April 30, 2024
• First Submitted That Met QC Criteria: May 16, 2024
• First Posted (Actual): May 17, 2024

Study Record Updates

• Last Update Posted (Actual): November 10, 2025
• Last Update Submitted That Met QC Criteria: November 5, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Lymphoma; T Cell Lymphoma; CD5KO CART5; Senza5 CART
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Hemic and Lymphatic Diseases; Lymphoma; Lymphoma, T-Cell
• Other Study ID Numbers: VIPER 101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No