CAR-T Cells Combined With Dasatinib for Patients With Relapsed and/or Refractory B-cell Hematological Malignancies

Официальное название

Clinical Trial for the Safety and Efficacy of CD19/BCMA-targeted CAR-T Cells Combined With Dasatinib for Patients With Relapsed and/or Refractory B-cell Acute Lymphoblastic Leukemia, B-cell Non-Hodgkin's Lymphoma and Multiple Myeloma

Обзор

A Study of CD19/BCMA-targeted CAR-T Cells Combined With Dasatinib for Patients With Relapsed and/or Refractory B-cell Acute Lymphoblastic Leukemia, B-cell Non-Hodgkin's Lymphoma and Multiple Myeloma.

Подробное описание

This is a double-arm, single-center study. This study is indicated for relapsed and/or refractory B-cell acute lymphoblastic leukemia, B-cell non-Hodgkin's lymphoma and multiple myeloma, the selections of dose levels and the number of subjects are based on clinical trials of similar foreign products. 120 patients will be enrolled for this trial. Primary objective is to explore the safety.

Вмешательства

• Препарат CD19/BCMA Targeted CAR T-cells and dasatinib
  Each subject receive CS1 Targeted CAR T-cells by intravenous infusion, and the dasatinib was combined according to the presumed regimens.
• Препарат CD19/BCMA Targeted CAR T-cells
  Each subject receive CS1 Targeted CAR T-cells by intravenous infusion.

Первичные конечные точки

• Dose-limiting toxicity (DLT) [Срок оценки: Baseline up to 28 days after CAR T-cells infusion]
• Incidence of treatment-emergent adverse events (TEAEs) [Срок оценки: Up to 2 years after CAR T-cells infusion]

Вторичные конечные точки (11)

• B-cell acute lymphocytic leukemia(B-ALL), Overall response rate (ORR) [Срок оценки: At Month 1, 3, 6, 12, 18 and 24]
• B-ALL, Overall survival (OS) [Срок оценки: Up to 2 years after CAR-T cells infusion]
• B-ALL, Event-free survival (EFS) [Срок оценки: Up to 2 years after CAR-T cells infusion]
• B cell non-hodgkin's lymphoma (B-NHL), Overall response rate (ORR) [Срок оценки: At Week 4, 12, and Month 6, 12, 18, 24]
• B-NHL, disease control rate (DCR) [Срок оценки: At Week 12 and Month 6, 12, 18, 24]
• Multiple myeloma (MM), Overall response rate (ORR) [Срок оценки: At Day 28]
• MM, Overall survival (OS) [Срок оценки: At Month 6, 12, 24]
• Quality of life [Срок оценки: At Baseline, Month 1, 3, 6, 9 and 12]
• Activities of Daily Living (ADL) score [Срок оценки: At Baseline, Month 1, 3, 6, 9 and 12]
• Instrumental Activities of Daily Living (IADL) score [Срок оценки: At Baseline, Month 1, 3, 6, 9 and 12]
• Hospital Anxiety and Depression Scale (HADS) score [Срок оценки: At Baseline, Month 1, 3, 6, 9 and 12]

Критерии участия

Критерии включения

• Histologically confirmed diagnosis of CD19+ ALL, CD19+ NHL, or BCMA+ MM per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines (2020.v2);
• Relapsed or refractory B cell hematological malignancies (meeting one of the following conditions):

• CR not achieved after standardized chemotherapy;
• CR achieved following the first induction, but CR duration is less than 12 months;
• Ineffectively after first or multiple remedial treatments;
• 2 or more relapses;
• Relapse after hematopoietic stem cell transplantation;
• Extramedullary leisions which were ineffective to radiotherapy or chemotherapy;
• Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit ofnormal, creatinine ≤ 176.8 umol/L;
• Echocardiogram shows left ventricular ejection fraction (LVEF) ≥50%;
• No active infection in the lungs, blood oxygen saturation in indoorair is ≥ 92%;
• Estimated survival time ≥ 12 weeks;
• ECOG performance status 0 to 2;
• Women of childbearing age had negative pregnancy test during screening period and before administration, and agreed to take effective contraceptive measures at least one year after infusion.
• Patients volunteer to participate in the study and sign the informed consent.

Критерии исключения

Subjects with any of the following exclusion criteria were not eligible for this trial:

• History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular, hemorrhagic diseases;
• Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
• Pregnant (or lactating) women;
• Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis);
• Active infection of hepatitis B virus or hepatitis C virus;
• Concurrent therapy with systemic steroids within 2 weeks prior toscreening, except for the patients recently or currently receiving in haledsteroids;
• Previously treated with any CAR-T cell product or other genetically-modified T cell therapies;
• Creatinine >2.5mg/dl, or ALT / AST > 3 times of normal amounts, or bilirubin >2.0 mg/dl;
• Other uncontrolled diseases that were not suitable for this trial;
• Patients with HIV infection;
• Any situations that the investigator believes may increase the risk of patients or interfere with the results of study.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The First Hospital of Zhejiang Medical Colleage Zhejiang University — Ханчжоу

Идентификаторы

NCT: NCT04603872 · DASA001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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