A Clinical Study to Investigate the Safety and Efficacy of CT0991 in Patients with Relapsed/Refractory Acute Myeloid Leukemia.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
CAR-T cells# chimeric antigen receptor T cells#
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, China
MTD and/or dose range
Evaluate Dose limited toxicity and recommended dosage range after CT0991 infusion.
Time frame: Up to 28 days after CAR-T cells infusion
Adverse Events (AE) after CT0991 infusion
An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria.
Time frame: 12 months after CT0991 infusion
Dose-limiting toxicity (DLT)
The DLT is evaluated as the proportion of patients who experienced adverse events related to CT0991 that meet the criteria for DLT events after the first infusion.
Time frame: Up to 28 days after CAR-T cells infusion.
Complete response (CR), complete response with partial hematologic recovery (CRh)
and complete response with incomplete hematologic recovery (CRi).Performed according to the Technical Guidelines for Clinical Development of New Drugs for Acute Myeloid Leukemia and ELN 2022 Criteria for AML defined of Achieve CR、CRh and CRi.
Time frame: 12 months after CT0991 infusion.
Morphologic leukemia-free status (MLFS) and partial response (PR)
Performed according to the Technical Guidelines for Clinical Development of New Drugs for Acute Myeloid Leukemia and ELN 2022 Criteria for AML defined of Achieve CRh, MLFS and PR.
Time frame: 12 months after CT0991 infusion
Duration of response (DOR)
Participants achieving CR/CRi/CRh will be included in the analysis set for DOR. DOR is defined as the time from the date of confirmed response until the date of disease relapse or death from any cause, whichever occurs first.
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Time frame: 12 months after CT0991 infusion.
Event-free survival (EFS)
Defined as the time from the date of receiving the infusion to the date of treatment failure (failure to achieve CR/CRh/CRi/MLFS/PR after both efficacy assessments), or relapse (hematologic relapse or extramedullary relapse after CR/CRh/CRi), or death from any cause, whichever occurs first. When an EFS event was "Ineffective Therapy", the primary analysis of EFS was performed on a 1-day basis (ie, time to treatment received as the event). For a more comprehensive assessment, sensitivity analyses could be performed using the actual date of treatment failure, end of treatment, or start of next-line anti-leukemia therapy as the end of EFS for treatment failure, respectively.
Time frame: 12 months after CT0991 infusion.
Overall survival (OS)
Defined as the time from the date of receiving the infusion to the date of death from any cause.
Time frame: 12 months after CT0991 infusion.
Minimal Residual Disease (MRD) Negative Rate
tested in all participants who achieved CR/CRh/CRi. MRD negativity was defined as abnormal cells detected by the MFC method accounting for \< 0.1% of CD45-positive cells.
Time frame: 12 months after CT0991 infusion.
Pharmacokinetic parameters of CT0991, including CAR copy number, peak value, AUC (area under the curve), in vivo persistence, etc.
Time to peak expansion, peak expansion, area under the curve (AUC) and duration in plasma after infusion of CT0991 cells.
Time frame: 12 months after CT0991 infusion.