A Clinical Study of Allogeneic CD19/BCMA CAR-T Cells for the Treatment of R/R B-cell Malignant Tumors

Официальное название

An Exploratory Clinical Study on the Safety and Efficacy of Allogeneic CD19/BCMA CAR-T Cell Treatment for Relapsed/ Refractory B-cell or Plasma Cell-derived Malignant Tumors

Обзор

A single arm, open-label pilot study is designed to determine the safety and efficacy of CD19 and B-cell maturation antigen (BCMA) targeted allogenic CAR-T cells (RN1101) in patients with relapsed/refractory B-cell or plasma cell-derived malignant tumors. 21 patients are planned to be enrolled in the dose-escalation trial. The primary objective of the study is to evaluation of the safety and feasibility of RN1101 for the treatment of relapsed/refractory B-cell or plasma cell-derived malignant tumors. The secondary objective is to evaluate the efficacy of RN1101 for the treatment of relapsed/refractory B-cell or plasma cell-derived malignant tumors. The exploratory objective is to evaluate expansion, persistence and ability of RN1101 to deplete CD19 or BCMA positive cells in patients with relapsed/refractory B-cell or plasma cell-derived malignant tumors.

Вмешательства

• Препарат RN1101 injection
  RN1101 injection is an allogenic CAR-T targeted CD19 and BCMA. A single infusion of CAR-T cells will be administered intravenously.

Первичные конечные точки

• Incidence and severity of adverse events after RN1101 infusion [Срок оценки: up to 24 weeks after RN1101 infusion]

Вторичные конечные точки (6)

• Percentage of MRD negative patients after RN1101 treatment [Срок оценки: 12 weeks, 24 weeks after RN1101 infusion]
• ORR (PR, VGPR, CR and sCR) of patients receive RN1101 treatment [Срок оценки: 12 weeks, 24 weeks after RN1101 infusion]
• Progression free survival after RN1101 treatment [Срок оценки: 12 weeks, 24 weeks after RN1101 infusion]
• CAR copies and cell count of CAR-T in blood and bone marrow (if available) after RN1101 treatment [Срок оценки: 12 weeks, 24 weeks after RN1101 infusion]
• Duration of response after RN1101 treatment [Срок оценки: 12 weeks, 24 weeks after RN1101 infusion]
• Overall survival after RN1101 treatment [Срок оценки: 12 weeks, 24 weeks after RN1101 infusion]

Критерии участия

Критерии включения

• Willingness to participate in the trial and provision of signed informed consent.
• Patients diagnosed with B-lymphocyte or plasma cell-derived malignancies as per the 2017 revised WHO criteria, including acute B-lymphoblastic leukemia (B-ALL), and mature B-cell lymphomas such as diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), marginal zone lymphoma (MZL), small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL), mantle cell lymphoma (MCL), multiple myeloma (MM), etc.
• Refractory or recurrent B-lymphocyte or plasma cell-derived malignancies, defined as failure to achieve complete remission after standard treatment, or relapse during follow-up after achieving remission with first-line or salvage therapy.
• Patients with B-cell acute lymphoblastic leukemia (ALL) who have achieved hematologic remission but have persistent minimal residual disease (MRD).
• According to the revised International Working Group (IWG) criteria, relapsed/refractory lymphoma patients must have at least one measurable lesion with a longest diameter ≥1.5 cm.
• 18 Years and older, regardless of gender.
• An expected survival of ≥12 weeks.
• Serum total bilirubin level < twice the upper limit of normal, serum creatinine level < upper limit of normal, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < three times the upper limit of normal.
• Absolute neutrophil count ≥0.5×10⁹/L, platelets ≥20×10⁹/L; for B-lymphocyte malignancies with definitive bone marrow involvement, no requirements for neutrophil and platelet counts.
• ECOG performance status of 0 - 2.
• Left ventricular ejection fraction (LVEF) ≥50% and no pericardial effusion.
• At least 2 weeks have passed since the last treatment (radiotherapy, chemotherapy, monoclonal antibody therapy, or other treatments).

Критерии исключения

• Known allergies, hypersensitivity, intolerance, or contraindications to CD19/BCMA allogenic CAR-T or any components of the trial drugs (including fludarabine, cyclophosphamide, and rituximab), or a history of severe allergic reactions.
• Recurrence after allogeneic hematopoietic stem cell transplantation with active graft - versus - host disease (GVHD) requiring steroid or immunosuppressive therapy.
• Severe active infection.
• Acquired or congenital immunodeficiency.
• New York Heart Association (NYHA) Class Ⅲ or Ⅳ heart failure.
• History of epilepsy or other central nervous system diseases.
• Lymphoma with extranodal involvement of the brain, lungs, or gastrointestinal tract.
• Other primary cancers, except:

• Non-melanoma skin cancer (e.g., basal cell carcinoma) cured by resection.
• Carcinoma in situ (e.g., cervical, bladder, or breast cancer) cured.
• Systemic high-dose steroids within 2 weeks before treatment.
• Pregnant, breastfeeding, or plans to become pregnant within 6 months.
• Participation in another clinical trial within the past month.
• Any situation the investigator deems may raise risks or interfere with trial results.

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

Китай · 1 центр

• Affiliated Hospital of Jiangsu University — Zhenjiang

Идентификаторы

NCT: NCT06976437 · RunNing

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗