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

NCT06786299 | Not Yet Recruiting Early Phase 1 DMC

• 1 other identifier: [2024]TXB NO.019
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Relapsed/Refractory Acute Myeloid Leukemia(AML)

Keywords

Relapsed/Refractory Acute Myeloid Leukemia(AML); CD84 Chimeric Antigen Receptor T-Cell Therapy

Outcome Measures

Primary Outcomes (1)

• Maximal tolerable dose (MTD）; Recommended phase II dose (RP2D）; Dose limiting toxicity （DLT）

  Dose limiting toxicity (DLT) is defined as an adverse event that is judged to be definitely or possibly related to RD-IIT-001, occurring from the first infusion of RD-IIT-001 up to Day 28 (±3 days). Safety evaluations are conducted using the NCI-CTCAE 5.0 criteria. Maximal tolerable dose (MTD）：Three dose levels （1.0×10\^6 cells/kg；3.0×10\^6 cells/kg；6.0×10\^6 cells/kg）are preset, with the observation period for dose-limiting toxicity (DLT) from the first infusion of RD-IIT-001 up to Day 28 (±3 days). Dose escalation follows the "3+3" design principle. Recommended phase II dose (RP2D）：After completing dose escalation, 3-6 additional subjects may be enrolled at the MTD dose level to determine the RP2D. If the MTD dose level has not been reached, the investigator may decide, based on PK and efficacy data, whether to increase to a higher dose or expand with 3-6 3-6 additional subjects at the current highest dose level to determine the RP2D.

  28 days ±3 days

Study Arms (1)

CD84-CART therapy arm

EXPERIMENTAL

Biological: RD-IIT-001; Drug: CD84-CART

Interventions

RD-IIT-001 BIOLOGICAL

Autologous CD84 Chimeric Antigen Receptor T-Cell Therapy

CD84-CART therapy arm

CD84-CART DRUG

Autologous CD84 Chimeric Antigen Receptor T-Cell Therapy

CD84-CART therapy arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ages 18-70 years (inclusive of boundary values), gender unrestricted.
• Voluntarily participate in this clinical study, sign the informed consent form, have good compliance, and cooperate with follow-up visits.
• Diagnosed with relapsed/refractory acute myeloid leukemia (AML), patients with relapsed/refractory AML must meet one of the following conditions: patients who have not achieved remission after two standard treatment courses; relapse within 12 months after complete remission; relapse after 12 months but have not achieved remission after one standard treatment; patients with second or subsequent relapses. Relapse is defined as the reappearance of leukemia cells in the peripheral blood or the presence of ≥5% blasts in the bone marrow (excluding other causes such as bone marrow regeneration after consolidation chemotherapy) or the infiltration of leukemia cells in extramedullary sites after achieving complete remission (CR) of AML, excluding cases where the above conditions occur after granulocyte colony-stimulating Factor （G-CSF） treatment.
• Flow cytometry confirms the presence of CD84-positive blasts.
• ECOG (Eastern Cooperative Oncology Group) score of 0-1.
• Able to collect T cells that meet the required specifications.
• Liver Function: Alanine Aminotransferase (ALT) ≤ 3 × Upper Limit of Normal (ULN); Aspartate Aminotransferase (AST) ≤ 3 × ULN; Total Bilirubin (TBIL) ≤ 1.5 × ULN (except in cases of Gilbert's syndrome).
• Renal Function: Creatinine Clearance Rate (CrCl) ≥ 60 ml/minute (Cockcroft/Gault formula).
• Coagulation Function: International Normalized Ratio (INR) ≤ 1.5 × Upper Limit of Normal (ULN), Prothrombin Time (PT) ≤ 1.5 × ULN.
• Cardiac Function: Hemodynamic stability is good, with a Left Ventricular Ejection Fraction (LVEF) ≥ 50%.
• Pulmonary Function: No clinically significant pleural effusion, baseline oxygen saturation \>92%.
• Female subjects of childbearing potential and male subjects with partners of childbearing potential must use medically recognized contraceptive measures or abstain from sexual activity during the study treatment period and for at least 6 months after the study treatment ends. Female subjects of childbearing potential must have a negative serum human chorionic gonadotropin （HCG） test within 7 days prior to study enrollment and must not be breastfeeding.

You may not qualify if:

• Individuals with a history of severe drug allergies or allergic constitution;
• Those with uncontrolled active infections;
• Individuals with severe cardiac diseases, such as angina, myocardial infarction, heart failure, and arrhythmias;
• Subjects with congenital immunoglobulin deficiencies;
• Patients with other malignant tumors (except for non-melanoma skin cancer, carcinoma in situ of the cervix, bladder cancer, and breast cancer with more than 5 years of disease-free survival);
• Subjects with end-stage renal failure;
• Subjects who are positive for Hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (HBcAb) with peripheral blood HBV DNA levels above the detection limit; those positive for Hepatitis C virus (HCV) antibody with peripheral blood HCV RNA positivity; individuals positive for Human Immunodeficiency Virus (HIV) antibody; and those with positive syphilis tests;
• Individuals with mental illnesses and severe cognitive impairments;
• Those who have participated in other clinical trials within the last month;
• Pregnant or breastfeeding women;
• Recipients of allogeneic transplants who relapsed within three months or still have graft-versus-host disease (GVHD) reactions more than three months after the transplant;
• Central nervous system leukemia involvement.

Sponsors & Collaborators

• First Affiliated Hospital of Zhejiang University: lead
• BRL Medicine Inc.: collaborator

Study Sites (1)

No. 79, Qingchun Road, Hangzhou City, Zhejiang Province.

Hangzhou, Zhejiang, 310003, China

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

Huafeng Wang, M.D.

CONTACT

86-13857147029; 1509036@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2025
• First Posted: January 22, 2025
• Study Start: February 10, 2025
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 22, 2025

Record last verified: 2025-01

Locations

CN (1)