Clinical Study on the Safety and Efficacy of Autologous CD84 Chimeric Antigen Receptor T-Cell Therapy for Adult Relapsed/Refractory Acute Myeloid Leukemia.

Overview

Acute Myeloid Leukemia (AML) is an aggressive type of leukemia, with high relapse rate and poor long term survival in adults. Traditional treatment regimens mainly include chemotherapy and hematopoietic stem cell transplantation. In the past decade, with the application of molecular targeted drugs and immunotherapy, the survival of AML patients has significantly improved. Relapsed/refractory (R/R)-AML is a state following the failure of AML treatment, with more complex therapy and poorer prognosis, necessitating more clinical trials and new treatment methods to improve patients' survival and quality of life. In this study, we propose a treatment approach that include therapying with autologous CD84 chimeric antigen receptor T-cell. Our study aims to answer the safety and efficacy of this treatment regimen, and further improve the survival for those participants.

This is a non-randomized, open-label, single-arm clinical study. A total of 12-18 adults aged 18-70 with relapsed/refractory acute myeloid leukemia (AML) participants will be enrolled. The primary endpoint is maximal tolerable dose(MTD), recommended phase II dose, and dose limiting toxicity (28 Days). The research process includes the screening period, apheresis period, lymphocyte depletion preconditioning period, treatment observation period, and follow-up period. Screening period (from signing the informed consent form to D-29): After the subject signs the informed consent form and before the apheresis period, various tests are conducted according to the requirements of the screening period. Subjects who fully meet the inclusion criteria and do not meet the exclusion criteria at all are included in the study. Apheresis period (D-28): After signing the informed consent form, eligible subjects need to undergo peripheral blood mononuclear cell (PBMC) collection before treatment, using a component blood collection method to circulate and collect no less than 1×10\^9 cells of PBMC to prepare RD-IIT-001. Lymphocyte depletion preconditioning period (D-5 to D-1): Five days before the first infusion of RD-IIT-001, a preconditioning assessment is conducted. After the assessment, qualified subjects undergo lymphocyte depletion preconditioning treatment before the first infusion of RD-IIT-001. The lymphocyte depletion preconditioning regimen is as follows: Fludarabine: 25 mg/m2, Day(D)-5, D-4, D-3, for three consecutive days by intravenous infusion; Cyclophosphamide: 300 mg/m2, D-5, D-4, for two consecutive days by intravenous infusion. Or the dosage of the lymphocyte depletion regimen may be adjusted according to the absolute value of peripheral blood lymphocytes. After lymphocyte depletion preconditioning, an assessment is conducted on D-1 before the infusion of RD-IIT-001. For subjects who are not suitable for the infusion of RD-IIT-001, the infusion may be suspended, and the infusion may be postponed for up to 7 days after the end of the lymphocyte depletion treatment. Treatment observation period (D0 to D28): After completing the assessment before the infusion of RD-IIT-001, qualified subjects receive a single one-time intravenous infusion of RD-IIT-001 on D0. Subjects who receive RD-IIT-001 infusion need to be observed in the hospital for at least 14 days. Those with a suitable donor and deemed eligible for transplantation by the study will proceed to undergo allogeneic hematopoietic stem cell transplantation. If not transplanted, patients will be followed up on D21 and D28 for safety and efficacy-related examinations. The period from the day of RD-IIT-001 infusion to day 28 (±3 days) is the DLT observation period. Follow-up period (D29 to M24): Starting from the second month after the first infusion of RD-IIT-001 and ending at the 24th month, the follow-up period involves assessing the effectiveness and safety of the subjects as well as survival follow-up according to the trial process schedule.