Study of TBI-2001(Autologous CD19 Specific Chimeric Antigen Receptor (CAR) Gene-transduced T Lymphocytes) for Relapsed or Refractory CD19+ B-cell Lymphoma, CLL/SLL

Официальное название

Phase I/Ib Study of TBI-2001 for Patients With Relapsed or Refractory CD19+ B-cell Lymphoma, Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL)

Обзор

This is a Phase 1/1b, open-label, dose-escalation study to evaluate the safety and the efficacy of anti-CD19 chimeric antigen receptor (CAR) (TBI-2001) for relapsed or refractory CD19+ B-cell lymphoma Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL).

Подробное описание

TBI-2001 is a next-generation CAR-T product including costimulatory sequences that lead to the activation of cytokine-related JAK/STAT signaling pathways. This is a first-in-human study of TBI-2001 and will follow a 3+3 design of dose-escalation cohorts. Additional subjects will be treated with TBI-2001 at the determined recommended phase 2 dose (RP2D) following cyclophosphamide and fludarabine pre-treatment. Long-term follow-up is conducted for 5 years following the infusion of TBI-2001

Вмешательства

• Биопрепарат TBI-2001
  Phase-I portion: cohort 1: 3×10\^5 cells/kg, cohort 2: 1×10\^6 cells/kg, cohort 3: 3×10\^6 cells/kg). Phase-Ib portion: The dose of Phase-Ib will be determined during the phase I portion.
• Препарат Cyclophosphamide
  IV Cyclophosphamide (for 3 days) will be administered as conditioning before cell infusion with TBI-2001.
• Препарат Fludarabine
  IV Fludarabine (for 3 days) will be administered as conditioning before cell infusion with TBI-2001.

Первичные конечные точки

• Safety of TBI-2001 [Срок оценки: One month]
• Safety of TBI-2001 [Срок оценки: One year]
• Safety of TBI-2001 [Срок оценки: One year]
• Recommended phase 2 dose (RP2D) of TBI-2001 [Срок оценки: One year]

Вторичные конечные точки (4)

• Efficacy of TBI-2001; Overall Response Rate (ORR) [Срок оценки: One year]
• Efficacy of TBI-2001; Durable Response Rate (DRR) [Срок оценки: One year]
• Efficacy of TBI-2001; Progression free survival (PFS) [Срок оценки: One year]
• Efficacy of TBI-2001; Overall survival (OS) [Срок оценки: One year]

Критерии участия

Критерии включения

• Patients with histologically or cytologically confirmed CD19 positive B cell Non-Hodgkin Lymphoma (NHL), Chronic Lymphocytic Leukemia (CLL), or Small Lymphocytic Lymphoma (SLL) who have received at least 2 prior therapies.
• Phase Ib cohort will enroll CLL/SLL patients only.
• ECOG Performance Status 0 or 1.
• Age ≥18 years at time of consent.
• Life expectancy greater than 4 months.
• For cessation of therapies prior to apheresis and lymphodepleting chemotherapy (bridging therapies), the institutional (UHN) SOPs related to Kymriah will be followed. However, an exception will be made for targeted and biological therapies that decrease circulating disease and are not expected to negatively impact successful harvest of lymphocytes by apheresis. In these cases, after discussion with and approval by the Sponsor, no washout will be required.
• Patients must have adequate key organ function (bone marrow, heart, lung, liver, renal, etc)
• Consent must be appropriately obtained in accordance with applicable local and regulatory requirements.
• The treating investigator should consider the patient to have disease that is incurable, and that the patient would be a reasonable candidate for future treatment with TBI-2001 within the next 3 months

Критерии исключения

• Uncontrolled intercurrent illnesses or medical conditions that may interfere with trial participation.
• Active or prior documented autoimmune disease within the past 2 years.
• History of primary immunodeficiency.
• History of organ transplant that requires use of immunosuppressive medications.
• History hypersensitivity to components of manufacture or excipients of investigational drug.
• Untreated central nervous system (CNS) metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation, and/or corticosteroids.
• Other invasive malignancy within 2 years except for noninvasive malignancies
• Current or prior use of immunosuppressive medication within 14 days before apheresis.
• Any condition that, in the opinion of the investigator, would interfere with the evaluation of TBI-2001 or interpretation of subject safety or study results.
• Known history of untreated active tuberculosis.
• HIV positivity.
• Active HTLV or syphilis infection.
• Active hepatitis B or active hepatitis C. Subjects with a negative PCR assay for viral load for hepatitis B or C are permitted.
• Pregnant or lactating women.
• Received allogeneic-HSCT.
• Any prior CD19 directed therapy.
• Live vaccine within 28 days prior to apheresis.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Канада · 1 центр

• Princess Margaret Cancer Centre — Toronto

Идентификаторы

NCT: NCT05963217 · TBI-200101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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