T-Cell Therapy (EB103) in Adults With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma (NHL)

Официальное название

An Open-Label, Dose Escalation, Multi-Center Phase I/II Clinical Trial of EB103 T-Cell Therapy in Adults With Relapsed/Refractory (R/R) B-Cell Non-Hodgkin's Lymphoma (NHL)

Обзор

This is an open-label, dose escalation, multi-center, Phase I/II clinical trial to assess the safety of an autologous T-cell therapy (EB103) and to determine the Recommended Phase II Dose (RP2D) in adult subjects (≥ 18 years of age) who have relapsed/refractory (R/R) B-cell NHL. The study will include a dose escalation phase followed by an expansion phase.

Подробное описание

This is an open-label, dose escalation, multi-center, Phase I/II clinical trial to assess the safety of EB103 and determine the RP2D in adult subjects (≥ 18 years of age) who have R/R B-cell NHL.

The study will include a dose escalation phase followed by an expansion phase. A traditional dose escalation model (3+3 design) will be used to determine the RP2D, and once determined, the expansion phase will commence. Additional subjects will be enrolled in the expansion phase to further confirm the safety profile of EB103 at the RP2D and evaluate the preliminary efficacy of EB103.

Вмешательства

• Биопрепарат EB103
  EB103 is an autologous T-cell therapy whereby a subject's own T cells are transduced with a lentiviral vector expressing the EB103 transgene.

Первичные конечные точки

• To assess the Dose Limiting Toxicities of EB103. [Срок оценки: Time Frame: 28 days]
• Incidence rates of Treatment-Emergent Adverse Events of EB103. [Срок оценки: Time Frame: 90 days]
• Incidence rates Treatment-Emergent Laboratory Abnormalities reported for EB103. [Срок оценки: Time Frame: 90 days]
• To determine the Recommended Phase II Dose (RP2D) of EB103. [Срок оценки: Time Frame: 21 months]

Вторичные конечные точки (9)

• To assess the Overall Response Rate of EB103 in our study subject population. [Срок оценки: Time Frame: Up to 2 years]
• To assess the Disease Control Rate of EB103 in our study subject population. [Срок оценки: Time Frame: Up to 2 years]
• To assess the Duration of Response of EB103 in our study subject population. [Срок оценки: Time Frame: Up to 2 years]
• To assess the Progression-Free Survival rate of EB103 in our study subject population. [Срок оценки: Time Frame: Up to 2 years]
• To assess the Event-Free Survival rate of EB103 in our study subject population. [Срок оценки: Time Frame: Up to 2 years]
• To assess the Overall Survival rate of EB103 in our study subject population. [Срок оценки: Time Frame: Up to 2 years]
• To characterize the pharmacokinetic (PK) profile of EB103 by measuring the peak exposure (Cmax). [Срок оценки: Time Frame: Up to 2 years]
• To characterize the pharmacokinetic (PK) profile of EB103 by measuring the time to reach peak exposure (Tmax). [Срок оценки: Time Frame: Up to 2 years]
• To characterize the pharmacokinetic (PK) profile of EB103 by measuring the partial area under the curve (pAUC). [Срок оценки: Time Frame: Up to 2 years]

Критерии участия

Критерии включения

• Age 18 years or older at the time of informed consent
• Histologically confirmed R/R B-cell non-Hodgkin's lymphoma (NHL)
• Adequate organ function
• Relapsed or refractory (R/R) disease defined as ONE OR MORE of the following:

• R/R after ≥ 2 lines of systemic therapy

• For the following NHL types: Burkitt lymphoma, Precursor B-cell lymphoblastic lymphoma, or Mantle cell lymphoma: R/R after ≥ 1 lines of systemic therapy
• Disease progression or recurrence ≤ 12 months after autologous hematopoietic stem cell transplantation (HSCT)
• For subjects who are considered transplant-ineligible: progressive disease as best response after ≥ 4 cycles of first-line therapy and stable disease as best response after ≥ 2 cycles of second-line (salvage) therapy; subject must have received an anti-CD20 monoclonal antibody and an anthracycline as one of their qualifying regimens
• All subjects must have received an appropriate chemoimmunotherapy regimen which at a minimum includes an:

• Anti-CD20 monoclonal antibody AND
• An anthracycline-containing chemotherapy regimen
• Positron emission tomography (PET)-positive disease according to Cheson 2014
• Eastern Cooperative Oncology Group (ECOG) ≤ 2
• Toxicities due to prior therapy must be stable and recovered to Grade 1 or less

Критерии исключения

• Prior CD19-targeted cellular therapy
• History of Richter's transformation of chronic lymphocytic leukemia (CLL)
• History of another primary malignancy that has not been in remission for ≥ 2 years.
• History or presence of clinically relevant Central Nervous System (CNS) pathology
• CNS disease which is progressing on most recent therapy or with a parenchymal mass which is likely to cause clinical symptoms
• Subjects with active cardiac lymphoma involvement which is not responding to treatment
• History of myocardial infarction, cardiac angioplasty and stenting, unstable angina, or other clinically significant cardiac disease within 6 months of informed consent
• Active, uncontrolled systemic bacterial, fungal, or viral infection. Patients with HIV, hepatitis B, or hepatitis C are eligible provided their infection is being treated and the viral load is controlled.
• History of autoimmune disease resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years
• History of severe, immediate hypersensitivity reaction to any agents used in this study, including the conditioning chemotherapeutic agents
• Venous thrombosis or embolism not managed on a stable regimen of anticoagulation
• Autologous HSCT within 3 months of informed consent
• Subjects with a prior allogeneic transplant at least 6 months prior to study enrollment are eligible unless experienced graft-versus-host disease (GvHD) that requires ongoing treatment with systemic steroids or other systemic GvHD therapy, such as a calcineurin inhibitor, within 12 weeks of initial screening
• Live vaccine within 3 months prior to planned start of conditioning regimen

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 2 центра

• University of California, Davis — Sacramento
• Baylor Scott & White Research Institute, Texas Oncology — Dallas

Идентификаторы

NCT: NCT06343311 · EBUS22CD19AR100

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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