A Clinical Study to Explore the Safety and Efficacy of CD33 CAR-T Cell in Relapsed/Refractory Acute Myeloid Leukemia

Обзор

A Clinical Study on the Safety and Effectiveness of targeting CD33 CAR-T Cell in the treatment of Relapsed/Refractory Acute Myeloid Leukemia

Подробное описание

This is a single-arm, open-label, dose-escalation clinical trial to evaluate the safety and efficacy of CD33 CAR-T Cell in patients with relapsed or refractory acute myeloid leukemia. It is planned to enroll 15-27 participants in this trial.

Вмешательства

• Биопрепарат CD33 CAR T-cells
  Each subject receive CD33 CAR T-cells by intravenous infusion

Первичные конечные точки

• Dose-limiting toxicity (DLT) [Срок оценки: Up to 28 days after Treatment]
• Incidence of treatment-emergent adverse events (TEAEs) [Срок оценки: Up to 2 years after Treatment]

Вторичные конечные точки (4)

• Complete response (CR), and complete response with incomplete hematologic recovery (CRi) [Срок оценки: Up to 12 weeks after CAR-T infusion]
• Duration of remission ,DOR [Срок оценки: Up to 1 years after CAR-T infusion]
• Overall survival, OS [Срок оценки: Up to 1 years after CAR-T infusion]
• Leukemia-Free Survival, LFS [Срок оценки: Up to 2 years after Treatment]

Критерии участия

Критерии включения

• 1\. Male or female, age ≥ 18 years old;
• 2\. CAR-T cells can be prepared normally, or who have failed to prepare autologous CAR-T cells (including the number of autologous lymphocytes <1×10\^9 or the expansion during the preparation process is insufficient or cannot reinfusion);
• 3\. Patients diagnosed with CD33 positive acute myeloid leukemia (AML) through histological or immunological examination，and CD33 positive expression rate >80%;
• 4\. Complies with the 2016 WHO classification for AML diagnosis and meets the diagnostic criteria for recurrence and refractory acute myeloid leukemia in the "Chinese Guidelines for the Diagnosis and Treatment of relapsed and refractory acute myeloid leukemia (2017 edition)", and currently there are no clinically relevant treatments or suitable clinical trials for registration:
• a) Diagnostic criteria for recurrent AML: After complete remission (CR), leukemia cells reappear in peripheral blood or primitive cells in bone marrow>0.050 (excluding other reasons such as bone marrow regeneration after consolidation chemotherapy) or leukemia cell infiltration appears outside the bone marrow;
• b) Diagnostic criteria for refractory AML: initial treatment cases that have failed to respond to two courses of standard protocol treatment; Patients who relapse within 12 months after consolidation and intensive treatment after CR; Patients who relapse after 12 months but fail conventional chemotherapy; Patients with 2 or more relapses; Persistent extramedullary leukemia;
• 5\. The number of primitive cells (promyelocytes and/or promyelocytes) in the bone marrow > 5% (morphology) and/or > 1% (flow cytometry detection);
• 6\. Total bilirubin ≤ 51 μmol / L, ALT and AST ≤ 3 times of the upper limit of normal value, serum creatinine ≤ 176.8 μmol / L；
• 7\. Echocardiography shows left ventricular ejection fraction (LVEF) ≥ 50%;
• 8\. There is no active pulmonary infection, and the oxygen saturation during air inhalation is more than 92%;
• 9\. The estimated survival time is more than 3 months;
• 10\. ECOG score was 0-2;
• 11\. Pregnant/lactating women, or male or female patients who have fertility and are willing to take effective contraceptive measures at least 6 months after the last cell infusion during the study period;
• 12\. Those who voluntarily participated in this trial and provided informed consent;

Критерии исключения

• 1\. Patients with the history of epilepsy or other CNS disease;
• 2\. Patients with prolonged QT interval time or severe heart disease;
• 3\. Active infection with no cure;
• 4\. Active infection of hepatitis B virus or C virus ;
• 5\. Before using any gene therapy products;
• 6\. The proiferation rate is less than 5 times response to CD3/CD28 co-stimulation signal;
• 7\. Suffering from other uncontrolled diseases that the researchers consider unsuitable for joining;
• 8\. Infected with AIDS virus;
• 9\. Any situation that researchers believe may increase the risk to the subjects or interfere with the 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

• The first affiliated hospital of medical college of zhejiang university — Ханчжоу

Идентификаторы

NCT: NCT06762132 · TXB2024025

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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