A Clinical Study of Allogenic CD19-CAR-T in the Treatment of R/R B-Cell Hematologic Malignancies

Официальное название

An Exploratory Clinical Study of the Safety and Efficacy of Allogenic CD19-Targeted Chimeric Antigen Receptor T-Cell Injection in the Treatment of Relapsed/Refractory B-Cell Hematologic Malignancies

Обзор

This is a single-arm, open-label pilot study to evaluate the safety and efficacy of CD19-targeted allogenic CAR-T cells (19UCART) in patients with relapsed/refractory B-cell hematologic malignancies. 12 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 19UCART for the treatment of relapsed/refractory B-cell hematologic malignancies. The secondary objective is to evaluate the efficacy of 19UCART for the treatment of relapsed/refractory B-cell hematologic malignancies. The exploratory objective is to evaluate expansion, persistence and ability of 19UCART to deplete CD19 positive cells in patients with relapsed/refractory B-cell hematologic malignancies.

Вмешательства

• Биопрепарат 19UCART injection
  19UCART injection is a CD19-targeted allogenic CAR-T. A single infusion of CAR-T cells will be administered intravenously.

Первичные конечные точки

• Toxicity and adverse-event grading after 19UCART treatment [Срок оценки: up to 12 months after infusion]
• CRS grading after 19UCART treatment [Срок оценки: up to 12 months after infusion]

Вторичные конечные точки (4)

• Overall response rate (ORR = CR + PR) of patients receive 19UCART treatment [Срок оценки: 1, 3, 6, and 12 months after infusion]
• Disease control rate (DCR = CR + PR + SD) of patients receive 19UCART treatment [Срок оценки: 1, 3, 6, and 12 months after infusion]
• PET-CT Response Criteria according to Lugano metabolic response categories [Срок оценки: 1, 3, 6, and 12 months after infusion]
• CAR copies and cell count of CAR-T in blood after 19UCART treatment [Срок оценки: Day 0, 1, 3, 5, 7, 9, 11, 14, 21, 28, and month 2, 3, 6, 9, 12 after infusion]

Критерии участия

Критерии включения

• Voluntary participation in this trial with signed informed consent.
• Diagnosis of B-cell hematologic malignancy according to the 2017 WHO classification, including B-acute 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), etc.
• Refractory or relapsed B-cell malignancy defined as failure to achieve complete remission after standard therapy, or relapse after achieving remission with first-line or salvage therapy.
• Persistence of minimal residual disease (MRD) positivity despite hematologic remission in B-cell acute lymphoblastic leukemia (ALL).
• At least one measurable lesion ≥1.5 cm in longest diameter by IWG revised criteria for relapsed/refractory lymphoma.
• Age 18-70 years; both sexes eligible.
• Expected survival ≥12 weeks.
• Adequate organ function as follows (no blood products or growth factors within 14 days before first infusion):

1). Hematology: A. White blood cell count (WBC) ≥3.0×10⁹/L B. Absolute neutrophil count (ANC) ≥1.5×10⁹/L C. Platelet count (PLT) ≥100×10⁹/L D. Hemoglobin (Hb) ≥90 g/L 2). Renal: A. Serum creatinine ≤1.5×ULN or calculated creatinine clearance ≥60 mL/min 3). Cardiac: A. Left ventricular ejection fraction (LVEF) ≥50 % B. QTc (Fridericia) ≤450 ms (men) or ≤470 ms (women) 4). Hepatic: A. Total bilirubin ≤1.5×ULN B. Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤2.5×ULN (≤5×ULN if liver involvement) 5). Coagulation: A. International normalized ratio (INR) or Prothrombin time (PT) ≤1.5×ULN B. Activated partial thromboplastin time (APTT) ≤1.5×ULN 6). Pulmonary: Diffusing capacity of the lung (DLCO) ≥50 % of predicted (with or without correction for anemia/alveolar volume).

9\. ECOG performance status 0-2 at screening. 10. LVEF ≥50 % and no pericardial effusion. 11. At least 2 weeks since last prior therapy (radiation, chemotherapy, monoclonal antibody, or other systemic treatment).

12\. Recovery to ≤CTCAE Grade 1 for any preceding serious adverse event (SAE). 13. WOCBP\* not surgically sterilized must use highly effective contraception from study start through 6 months after last dose; men with WOCBP partners must use highly effective contraception through 3 months after last dose. WOCBP must have negative serum β-hCG within 7 days before first dose and must not be breastfeeding.

14\. Ability to comply with study visit schedule and all protocol requirements.

\*WOCBP = women of child-bearing potential

Критерии исключения

• Subjects with any of the following conditions are ineligible for this trial:

• Known hypersensitivity, allergic reaction, intolerance, or contraindication to 19UCART or any study-drug component (including fludarabine, cyclophosphamide, or tocilizumab), or history of severe anaphylaxis.
• Post-allo-HSCT relapse with active graft-versus-host disease requiring systemic corticosteroids or other immunosuppressants.
• Uncontrolled active infection of any etiology.
• Active hepatitis B, hepatitis C, or tuberculosis.
• HIV or syphilis infection.
• Active autoimmune disease or history of severe autoimmune disorder (as judged by the PI) requiring prolonged immunosuppressive therapy.
• Congenital or acquired immunodeficiency syndromes.
• New York Heart Association (NYHA) class III or IV heart failure, unstable angina, myocardial infarction within 6 months, or sustained (>30 s) ventricular arrhythmia.
• History of epilepsy or other significant central nervous system disorders.
• Extra-nodal lymphomatous involvement of brain, lung, or gastrointestinal tract.
• Prior malignancy other than:

• Curatively resected non-melanoma skin cancer (e.g., basal-cell carcinoma)
• Curatively treated carcinoma in situ (cervical, bladder, breast, etc.)
• Systemic high-dose corticosteroids within 2 weeks before study entry.
• Pregnancy, lactation, or intention to become pregnant within 6 months.
• Participation in another clinical trial within 1 month.
• Anticipated need for any other systemic anti-neoplastic therapy during the study.
• Major surgery within 14 days before first study-drug administration.
• Any condition that, in the investigator's opinion, could increase patient risk or interfere with study 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: NCT07316907 · EU19

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗