A Study of Murine CD19 CAR-T Therapy for Patients With Relapsed or Refractory CD19+ B-cell Hematological Malignancies

Официальное название

Clinical Trial for the Safety and Efficacy of Murine CD19 CAR-T Cells Therapy for Patients With Relapsed and/or Refractory B-cell Acute Lymphoblastic Leukemia and B-cell Non-Hodgkin's Lymphoma

Обзор

A Study of Murine CD19 CAR-T Cells Therapy for Patients With Relapsed or Refractory CD19+ B-cell Hematological Malignancies.

Подробное описание

This is a single arm, open-label, single-center study. This study is indicated for relapsed or refractory CD19+ B-cell hematological malignancies, including acute lymphoblastic leukemia and B-cell non-Hodgkin's lymphoma. The selections of dose levels and the number of subjects are based on clinical trials of similar foreign products. Two groups of patients will be enrolled, 36 in each group. Primary objective is to explore the safety, main consideration is dose- related safety.

Вмешательства

• Препарат Murine CD19 CAR-T cells
  Each subject receive murine CD19 CAR T-cells by intravenous infusion

Первичные конечные точки

• Dose-limiting toxicity (DLT) [Срок оценки: Baseline up to 28 days after murine CD19 targeted CAR T-cells infusion]
• Incidence of treatment-emergent adverse events (TEAEs) [Срок оценки: Up to 2 years after murine CD19 targeted CAR T-cells infusion]

Вторичные конечные точки (9)

• 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 murine CD19 CAR-T cells infusion]
• B-ALL, Event-free survival (EFS) [Срок оценки: Up to 2 years after murine CD19 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]
• 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

• Inclusion criteria only for B-ALL:

• Histologically confirmed diagnosis of CD19+ B-ALL per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Lymphoblastic Leukemia (2016.v1)；
• Relapsed or refractory CD19+ B-ALL (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;
• The number of primordial cells (lymphoblast and prolymphocyte) in bone marrow is > 5% (by morphology), and/or > 1% (by flow cytometry);
• Philadelphia-chromosome-negative (Ph-) patients; or Philadelphia-chromosome-positive (Ph+) patients who cannot tolerate TKI treatments or do not respond to 2 TKI treatments;
• Inclusion criteria only for B-NHL:

• Histologically confirmed diagnosis of DLBCL (NOS), FL, DLBCL transformed from CLL/SLL, PMBCL, and HGBCL per the WHO Classification Criteria for Lymphoma (2016);
• Relapsed or refractory B-NHL (meeting one of the following conditions):

• No response or relapse after second-line or above chemotherapy regimens;
• Primary drug resistance;
• Relapse after auto-HSCT;
• At least one assessable tumor lesion per Lugano 2014 criteria;
• Common inclusion criteria for B-ALL and B-NHL:

• Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit of normal, creatinine ≤ 176.8 umol/L;
• Echocardiogram shows left ventricular ejection fraction (LVEF) ≥ 50%;
• No active infection in the lungs, blood oxygen saturation in indoor air is ≥ 92%;
• Estimated survival time ≥ 3 months;
• ECOG performance status 0 to 2;
• Patients or their legal guardians 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 tractinfectionand bacterial pharyngitis);
• Active infection of hepatitis B virus or hepatitis C virus;
• Concurrent therapy with systemic steroids within 2 weeks prior to screening, except for the patients recently or currently receiving in haled steroids;
• 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

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The First Affiliated Hospital，College of Medicine, Zhejiang University — Ханчжоу

Идентификаторы

NCT: NCT04532281 · mCD19-002

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗