## Protocol Section
### Identification Module
**NCT ID:** NCT06420089

**Acronym:** VIPER101

**Brief Title:** 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

#### Organization Study ID Info
**ID:** VIPER 101
#### Organization
**Class:** INDUSTRY
**Full Name:** Vittoria Biotherapeutics
### Status Module
#### Completion Date
**Date:** 2027-06-30

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-17

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-16

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-06-30

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06-30

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-17
**Type:** ACTUAL
**Study First Submit Date:** 2024-04-30
**Study First Submit QC Date:** 2024-05-16
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** University of Pennsylvania

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Vittoria Biotherapeutics

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Oversight Has DMC:** True

### Description Module

**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.

### Conditions Module

**Conditions:**

- T Cell Non-Hodgkin Lymphoma

### Design Module

#### Design Info

**Allocation:** NON_RANDOMIZED

**Intervention Model:** SEQUENTIAL

**Intervention Model Description:** Open label

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 30

**Type:** ESTIMATED

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Four treatment arms with Standard of Care Lymphodepletion:

Fludarabine 25mg/m2 IV for 3 days Cyclophosphamide 250mg/m2 IV for 3 days

**Intervention Names:**

- Drug: Senza5 CART5

**Label:** Senza5 CART5 with standard of care lymphodepletion

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Four treatment arms in patients are lymphopenic into the corresponding dose level.

**Intervention Names:**

- Drug: Senza5 CART5

**Label:** Senza5 CART5 without standard of care lymphodepletion

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Senza5 CART5 with standard of care lymphodepletion

- Senza5 CART5 without standard of care lymphodepletion

**Description:** The Senza5 CART5 drug product consists of a dual population of engineered autologous T cells: CD5 knockout (KO)cells and CD5KO-CART5 cells

**Name:** Senza5 CART5

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Measure the occurrence of Dose Limiting Toxicity events of each dose level per arm

**Measure:** Determine the recommended phase 2 dose (RP2D) of Senza5 CART5 cells

**Time Frame:** 12 months

#### Secondary Outcomes

**Description:** Quantify quantifying the type and frequency of adverse events

**Measure:** Determine the safety of Senza5 CART5 cells

**Time Frame:** 12 months

**Description:** Quantify the safety and tolerability of the highest dose

**Measure:** Determine the maximum tolerated dose (MTD)

**Time Frame:** 12 months

**Description:** Quantify the number of product release failures and occurrence of dose failures (inability to meet targeted dose)

**Measure:** Determine the manufacturing feasibility of Senza5 CART5

**Time Frame:** 12 months

**Description:** Measure the objective response rate

**Measure:** Determine efficacy of Senza5 CART5

**Time Frame:** 12 months

**Description:** Measure the complete response rate

**Measure:** Determine efficacy of Senza5 CART5

**Time Frame:** 12 months

**Description:** Measure the best overall response

**Measure:** Determine efficacy of Senza5 CART5

**Time Frame:** 12 months

**Description:** Measure the duration of response

**Measure:** Determine efficacy of Senza5 CART5

**Time Frame:** 12 months

**Description:** Measure the overall survival

**Measure:** Determine efficacy of Senza5 CART5

**Time Frame:** 12 months

**Description:** Measure the progression free survival

**Measure:** Determine efficacy of Senza5 CART5

**Time Frame:** 12 months

### Eligibility Module

**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.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** ClinOps@vittoriabio.com

**Name:** Vittoria Biotherapeutics, MD, PhD

**Phone:** (215) 600-1380

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Philadelphia

**Country:** United States

**Facility:** Vittoria Biotherapeutics

**State:** Pennsylvania

**Zip:** 19104

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000008232

- Term: Lymphoproliferative Disorders

- ID: D000008206

- Term: Lymphatic Diseases

- ID: D000007160

- Term: Immunoproliferative Disorders

- ID: D000007154

- Term: Immune System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC15

- Name: Blood and Lymph Conditions

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M11220

- Name: Lymphoma

- Relevance: HIGH

- As Found: Lymphoma

- ID: M18829

- Name: Lymphoma, T-Cell

- Relevance: HIGH

- As Found: T-cell non-Hodgkin lymphoma

- ID: M11222

- Name: Lymphoma, Non-Hodgkin

- Relevance: HIGH

- As Found: Non-Hodgkin Lymphoma

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M11225

- Name: Lymphoproliferative Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M11203

- Name: Lymphatic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10206

- Name: Immunoproliferative Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M10200

- Name: Immune System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T3543

- Name: Lymphosarcoma

- Relevance: HIGH

- As Found: Lymphoma

### Condition Browse Module - Meshes

- ID: D000008223

- Term: Lymphoma

- ID: D000008228

- Term: Lymphoma, Non-Hodgkin

- ID: D000016399

- Term: Lymphoma, T-Cell

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: ARhu

- Name: Antirheumatic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M6727

- Name: Cyclophosphamide

- Relevance: LOW

- As Found: Unknown

- ID: M283230

- Name: Fludarabine

- Relevance: LOW

- As Found: Unknown

- ID: M225513

- Name: Fludarabine phosphate

- Relevance: LOW

- As Found: Unknown

- ID: M2853

- Name: Immunomodulating Agents

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
