EX02 CAR-T Cells for Relapsed and Refractory Acute Myeloid Leukemia

Official title

An Open-label, Single-arm Clinical Study of EX02 CAR-T Therapy for Relapsed and Refractory Acute Myeloid Leukemia

Overview

This is a early Phase 1 open-label, single-arm clinical study of EX02 CAR-T therapy for relapsed and refractory acute myeloid leukemia. Each participant will undergo leukapheresis after enrolment, receive treatment of the conditioning chemotherapy of cyclophosphamide and fludarabine, and an an intravenous infusion of CAR-T cells. Each participant will proceed through the following study procedures: * Screening * Enrollment/Leukapheresis * Conditioning chemotherapy * CAR T treatment * Post-treatment assessment * Long-term follow-up

Interventions

• Biological CAR-T Cell Injection
  Conditioning chemotherapy: Lymphodepletion regimen consisting of fludarabine 25 mg/m2/day and cyclophosphamide 250 mg/m2/day for 3 consecutive days, administered 48 hours before intraperitoneal infusion. On the day of administration, premedication with 500mg of acetaminophen orally and 20mg of promethazine intramuscularly or intravenously (or other non-steroidal anti-inflammatory drugs and antihistamines) should be given 30 minutes before intraperitoneal infusion. The therapeutic dose of CAR-T

Primary outcome measures

• Treatment-Emergent Adverse Events (TEAE) [Time frame: From the infusion (Day 0) to 3 months]
• Overall Response Rate (ORR) [Time frame: From the infusion (Day 0) to Day 60]

Secondary outcome measures (3)

• PFS [Time frame: 12 months]
• OS [Time frame: 12 months]
• ECOG scoring [Time frame: 2 months]

Eligibility criteria

Inclusion criteria

• According to the Chinese Adult Acute Myeloid Leukemia (AML) Diagnosis and Treatment Guidelines (2023 edition/previous edition), patients diagnosed with acute myeloid leukemia (AML) and meeting the diagnostic criteria for refractory AML are eligible, including: initial treatment cases with no response after two courses of standard therapy; relapse within 12 months after achieving complete remission (CR) and failure of consolidation therapy; relapse after 12 months with no response to conventional chemotherapy; two or more relapses; and presence of extramedullary leukemia.
• Peripheral blood, bone marrow, or extramedullary lesion specimens showing leukemia cells with positive surface expression of EX02;
• ECOG performance status score of 0-2;
• Age ≥18 and ≤70 years, any gender;
• Blood cell examination meeting the following conditions: hemoglobin > 60g/L, normal T lymphocyte count (CD3+) > 0.5×10\^9/L, platelet count > 30×10\^9/L;
• Negative pregnancy test for women of childbearing potential before the start of the trial, and agreement to use effective contraception measures during the trial until the final follow-up; male participants of reproductive potential agreeing to use effective contraception measures during the trial until the final follow-up;
• Voluntary participation in this clinical study: after fully understanding the study content, voluntary signing of the informed consent form, and commitment to complete all trial procedures and activities.

Exclusion criteria

• Active hepatitis A, B, C, HIV infection, or other severe active infections that are not yet controlled;
• History of acquired immune deficiency syndrome (AIDS) or long-term use of immunosuppressants due to other diseases (including steroids, equivalent to prednisone >15mg/day);
• Conditions of the heart function: a. New York Heart Association (NYHA) class III or IV heart failure; b. Myocardial infarction or coronary artery bypass surgery within the six months prior to enrollment; c. Clinically significant ventricular arrhythmia or unexplained syncope; d. History of severe non-ischemic cardiomyopathy; e. History of cardiac dysfunction (left ventricular ejection fraction <45%) within 8 weeks before enrollment;
• Pregnant or lactating women; participants (both male and female) unwilling to use contraception;
• Severe liver or kidney dysfunction: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels exceeding 3 times the upper limit of normal, bilirubin exceeding 3 times the upper limit of normal; serum creatinine ≥ 178 μmol/L (decompensated phase);
• History of severe allergic reactions to any drugs planned for use in this study;
• Recipients of hematopoietic stem cell transplantation must have discontinued immunosuppressants for at least 6 weeks before enrollment and have no signs of graft-versus-host disease;
• Other conditions deemed unsuitable for participation in this trial by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The Second Affliated Hospital of Anhui Medical University — Hefei

Identifiers

NCT: NCT06642025 · TXB2024-001(F1)

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗