A Clinical Study to Explore the Safety and Efficacy of CT0991 in Relapsed/ Refractory Acute Myeloid Leukemia

Официальное название

A Clinical Study to Investigate the Safety and Efficacy of CT0991 in Patients With Relapsed/Refractory Acute Myeloid Leukemia.

Обзор

A Clinical Study to Investigate the Safety and Efficacy of CT0991 in Patients with Relapsed/Refractory Acute Myeloid Leukemia.

Подробное описание

This is a single-arm, open-label, dose-escalation clinical trial to evaluate the safety, efficacy, and cellular pharmacokinetics of CT0991 in patients with relapsed or refractory acute myeloid leukemia. It is planned to enroll 3-24 participants in this trial.

Вмешательства

• Препарат CT0991 CAR-T cells infusicn
  CAR-T cells# chimeric antigen receptor T cells#

Первичные конечные точки

• MTD and/or dose range [Срок оценки: Up to 28 days after CAR-T cells infusion]
• Adverse Events (AE) after CT0991 infusion [Срок оценки: 12 months after CT0991 infusion]
• Dose-limiting toxicity （DLT） [Срок оценки: Up to 28 days after CAR-T cells infusion.]

Вторичные конечные точки (7)

• Complete response (CR), complete response with partial hematologic recovery (CRh) [Срок оценки: 12 months after CT0991 infusion.]
• Morphologic leukemia-free status (MLFS) and partial response (PR) [Срок оценки: 12 months after CT0991 infusion]
• Duration of response （DOR) [Срок оценки: 12 months after CT0991 infusion.]
• Event-free survival (EFS) [Срок оценки: 12 months after CT0991 infusion.]
• Overall survival (OS) [Срок оценки: 12 months after CT0991 infusion.]
• Minimal Residual Disease (MRD) Negative Rate [Срок оценки: 12 months after CT0991 infusion.]
• Pharmacokinetic parameters of CT0991, including CAR copy number, peak value, AUC (area under the curve), in vivo persistence, etc. [Срок оценки: 12 months after CT0991 infusion.]

Критерии участия

Критерии включения

• Volunteer to participate in the clinical trial; Fully understand and are informed of this study and sign the informed consent form; Willing to follow and able to complete all trial procedures.
• Age 18-75 years (inclusive), male or female.
• Estimated survival > 12 weeks.
• Patients with relapsed or refractory AML as defined in the Chinese Guidelines for the Diagnosis and Treatment of Relapsed and Refractory Acute Myeloid Leukemia (Version 2023);
• Flow cytometry or immunohistochemical examination of bone marrow or peripheral blood samples showed positive expression of CD38 in tumor cells and the expression rate was ≥80%.
• ECOG score 0-2.
• Participants should meet the following test results (no ongoing supportive care):

• Left ventricular ejection fraction (LVEF) > 50%;
• ALT≤ 2.5 × ULN, AST ≤ 2.5 × ULN, total bilirubin ≤ 2 × ULN;
• Endogenous creatinine clearance ≥ 30 mL/min (creatinine clearance calculated using the Cockcroft-Gault formula);
• Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN and prothrombin time (PT) ≤ 1.5 × ULN.

Критерии исключения

• The participant has any serious illness, laboratory abnormality, or psychiatric disorder that may impair the ability to receive or tolerate planned trial treatment; or the investigator judges that the participant's participation in the clinical trial is not in his/her best interest (e.g.,compromised health), or may hinder, limit, or confound protocol-specific Assessments.
• Participants were diagnosed with acute promyelocytic leukemia (APL),BCR-ABL positive leukemia (chronic myeloid leukemia in acute phase),secondary AML (other than MDS), central nervous system leukemia.
• Participants with a history of epilepsy or other central nervous system disease;
• Participants who have previously received autologous or allogeneic CAR-T therapy.
• Participants who have received autologous stem cell transplantation or allogeneic stem cell transplantation within 12 weeks.
• Participants who have received prior immunotherapy targeting CD38.
• Participant has clinically significant active GVHD or is receiving systemic corticosteroids for GVHD.
• Participant has any of the following at screening:

1)Active, uncontrolled systemic infection or requiring intravenous anti-infective agents.

2)Any of the following cardiac conditions, including:

• New York Heart Association Class III-IV heart failure;
• History of myocardial infarction, coronary artery bypass grafting, or unstable angina within 6 months prior to Qinglin;
• History of uncontrolled arrhythmia of significant clinical significance (as judged by the investigator), such as ventricular arrhythmia;
• History of severe nonischemic ardiomyopathy;
• Other cardiac disease that the investigatorbelieve could jeopardize the participant 's well-being or compromise participation in this clinical trial; 3) Active bleeding of clinical significance as judged by the investigator; 4)Requiring supplemental oxygen to maintain oxygen saturation> 92%; 5)Patients with severe chronic obstructive pulmonary disease (COPD) or other lung diseases that cannot tolerate CAR-T treatment as judged by the investigator.

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

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Ухань

Идентификаторы

NCT: NCT07233018 · CT0991-CG9001_01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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