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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат 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

Первичные конечные точки

• Determine the recommended phase 2 dose (RP2D) of Senza5 CART5 cells [Срок оценки: 12 months]

Вторичные конечные точки (9)

• Determine the safety of Senza5 CART5 cells [Срок оценки: 12 months]
• Determine the maximum tolerated dose (MTD) [Срок оценки: 12 months]
• Determine the manufacturing feasibility of Senza5 CART5 [Срок оценки: 12 months]
• Determine efficacy of Senza5 CART5 [Срок оценки: 12 months]
• Determine efficacy of Senza5 CART5 [Срок оценки: 12 months]
• Determine efficacy of Senza5 CART5 [Срок оценки: 12 months]
• Determine efficacy of Senza5 CART5 [Срок оценки: 12 months]
• Determine efficacy of Senza5 CART5 [Срок оценки: 12 months]
• Determine efficacy of Senza5 CART5 [Срок оценки: 12 months]

Критерии участия

Критерии включения

• 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.
• No circulating CD5+ malignant cells identified by peripheral blood flow cytometry must be present.

Критерии исключения

• 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.
• History of immunodeficiency.
• 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.
• Active and/or systemic inflammatory or autoimmune diseases.
• Signs or symptoms indicative of active CNS involvement.
• 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.
• Clinically apparent arrhythmia, or arrhythmias that are not stable on medical management
• 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.
• Prior monoclonal antibody therapy within 4 weeks prior to study Day 1
• Prior use of alemtuzumab
• Prior chemotherapy targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1
• Uncontrolled active infection requiring systemic therapy.
• Circulating CD5+ malignant cells identified by peripheral blood flow cytometry present.
• Active and/or systemic inflammatory or autoimmune diseases.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 2 центра

• Columbia University Irving Medical Center — New York
• University of Pennsylvania - Abramson Caner Center — Philadelphia

Идентификаторы

NCT: NCT06420089 · VIPER 101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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