BAFFR-targeting CAR T Cells for Patients With Relapsed or Refractory B-NHL

Официальное название

A Phase 1 Study Evaluating BAFFR-targeting CAR T Cells for Patients With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma (B-NHL)

Обзор

A Phase 1 Study Evaluating BAFFR-targeting CAR T Cells for Patients with Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma (B-NHL)

Подробное описание

This phase I trial evaluates the side effects and best dose of BAFFR-CAR T cells in treating patients with B-cell Non-Hodgkin's Lymphoma (B-NHL) that has come back (recurrent) or does not respond to treatment (refractory). T cells are infection fighting blood cells that can kill cancer cells. The T cells given in this study will come from the patient and will have a new gene put in them that makes them able to recognize BAFFR, a protein on the surface of cancer cells. These BAFFR-specific T cells may help the body's immune system identify and kill BAFFR+ cancer cells.

Вмешательства

• Биопрепарат BAFFR-CAR T cells
  First-in-human trial examining the safety and preliminary efficacy of BAFFR-CAR T cells in participants with r/r B-NHL

Первичные конечные точки

• Incidence of adverse events [Срок оценки: Up to 1 year post treatment]
• Maximum Tolerated Dose (MTD) [Срок оценки: The DLT evaluation period is defined as 28 days following BAFFR CAR-T infusion.]

Вторичные конечные точки (5)

• Disease Response [Срок оценки: Up to 1 year post treatment]
• Minimal Residual Disease (MRD) [Срок оценки: Up to 1 year post treatment]
• B Cell Quantification [Срок оценки: Up to 1 year post treatment]
• Progression-free survival (PFS) [Срок оценки: From CAR T cell infusion to the first observation of disease relapse/progression or death from any cause, whichever occurs first, assessed up to 15 years.]
• Overall Survival (OS) [Срок оценки: From the day of BAFFR-CAR T cell infusion to death from any cause assessed, up to 15 years.]

Критерии участия

Критерии включения

• Informed Consent: Signed informed consent by the participant or legally authorized representative.
• Age \& Performance Status:

• Age ≥ 18 years
• ECOG performance status ≤ 2
• Diagnosis \& Disease Criteria:

• Histologically confirmed B-NHL, including LBCL, MCL, and FL/MZL subtypes meeting specified prior treatment conditions.
• BAFF-R expression on lymphoma cells required.
• Measurable Disease: Tumor ≥1.5 cm on CT/PET scan or evidence of disease in blood, BM, GI, skin, or spleen.
• Prior CAR T-cell Therapy: Allowed if ≥ 3 months since last treatment and CD19 CAR-T persistence < 5% before leukapheresis.
• Organ Function \& Laboratory Criteria:

• Hematologic: ANC ≥ 1000/μL, Platelets ≥ 75,000/μL (exceptions for BM involvement).
• Liver Function: Bilirubin ≤ 1.5x ULN (except Gilbert's), AST/ALT < 3x ULN.
• Renal Function: CrCl ≥ 50 mL/min.
• Cardiac \& Pulmonary: LVEF ≥ 45%, QTcF ≤ 480 ms, O₂ saturation > 91% on room air.
• Infectious Disease Screening: Seronegative for HIV, active HBV, active HCV (or undetectable viral load if positive).
• Reproductive Considerations:

• Negative pregnancy test for females of childbearing potential.
• Use of effective contraception or abstinence through 3 months post-treatment.

Критерии исключения

• Prior Therapies \& Transplants:

• Prior allogeneic SCT.
• Autologous SCT < 6 months before leukapheresis.
• Concurrent systemic steroids or chronic immunosuppressant use.
• Disease-Specific Exclusions:

• Cardiac lymphoma involvement.
• Need for urgent therapy due to tumor-related complications (e.g., bowel obstruction).
• Medical Conditions:

• Active autoimmune disease requiring immunosuppressants.
• Primary immunodeficiency.
• Cardiac conditions, including NYHA Class III/IV heart disease, arrhythmia, recent MI (≤ 6 months), stroke (≤ 6 months), or significant VTE (≤ 6 months).
• Neurologic conditions, including prior optic neuritis, CNS inflammatory diseases, or seizure disorders.
• History of malignancy, unless resected/treated with curative intent or in remission for ≥ 3 years.
• Uncontrolled systemic infections or active CNS lymphoma.
• Pregnancy \& Breastfeeding: Females who are pregnant or nursing.
• Other Considerations:

• Investigator-determined safety concerns.
• Potential noncompliance with study procedures.

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

США · 6 центров

• City of Hope Medical Center — Duarte
• Stanford University — Stanford
• University of Kansas Hospital — Kansas City
• University of Minnesota — Minneapolis
• Atrium Health Levine Cancer Institute - Morehead — Charlotte
• Providence Swedish Cancer Institute — Seattle

Публикации

• Dong Z, Budde LE, Oh E, Szymura S, Anderson A, Del Real M, Cha SC, Forman SJ, Kwak LW, Wang X. Analysis of polyfunctionality for enhanced BAFF-R CAR T-cell therapy for hematologic malignancies. Blood Adv. 2024 Aug 13;8(15):4066-4076. doi: 10.1182/bloodadvances.2024013195. PMID 38885481

Идентификаторы

NCT: NCT05370430 · PMB-102 · PMB-BAFFR-102

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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