Using CAR-T cell therapy targeting Tim-3 and CD123 for treating relapsed acute myeloid leukemia

Application of Anti Tim-3/CD123 CAR-T Cell Therapy in Relapsed and Refractory Acute Myeloid Leukemia (rr/AML)

This study is testing a new CAR-T cell therapy that targets specific markers in people aged 18-70 with relapsed acute myeloid leukemia to see if it can safely improve their treatment outcomes.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Xuzhou Medical University (Academic / other)
• Drugs / interventions: CAR-T
• Locations: 1 site (Xuzhou, Jiangsu)
• Trial ID: NCT06125652 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and efficacy of a novel CAR-T cell therapy that targets both Tim-3 and CD123 in patients with relapsed and refractory acute myeloid leukemia (AML). By focusing on Tim-3, which is highly expressed on leukemia stem cells but not on normal hematopoietic stem cells, the therapy aims to improve specificity and reduce harmful side effects associated with traditional CD123-targeting CAR-T cells. Participants will undergo treatment with these engineered T cells, and their responses will be closely monitored to assess both safety and effectiveness. The study is designed for patients aged 18-70 who have experienced relapse or refractory AML.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18-70 with a diagnosis of relapsed or refractory acute myeloid leukemia who have recovered from prior treatment toxicity.

Not a fit: Patients with acute promyelocytic leukemia or those with a history of central nervous system disorders may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a more targeted and effective treatment option for patients with relapsed and refractory AML, potentially improving survival rates and quality of life.

How similar studies have performed: While CAR-T cell therapies have shown promise in treating various cancers, this specific approach targeting both Tim-3 and CD123 is novel and has not been extensively tested in previous studies.

Eligibility criteria

Inclusion Criteria:

1. All subjects must sign and date the Informed Consent before initiating any study specific procedures or activities;
2. At the age of 18-70 years old;
3. Diagnosed as relapse/refractory (r/r) de novo or secondary acute myeloid leukemia (AML);
4. The patient has recovered from the toxicity of previous treatment;
5. ECOG score ≤ 2 and expected survival period is not less than 3 months;
6. Adequate organ function defined as:AST ≤3×ULN; ALT ≤3×ULN; Total bilirubin ≤1.5×ULN; Serum creatinine ≤1.5×ULN, or CCR≥60 mL/min; Hemoglobin ≥60g/L ; Indoor oxygen saturation ≥92%; LVEF≥45%;
7. Pregnancy testing: females of childbearing potential must have a negative serum or urine pregnancy test;
8. From the use of study drug to 2 years after treatment, males and female of childbearing potential must agree to use an effective method of contraception.

Exclusion Criteria:

1. Diagnosis of acute promyelocytic leukemia;
2. History or presence of a CNS disorder;
3. HBsAg is positive; HCV #HIV or Syphilis antibody are positive, CMV-DNA in peripheral blood is more than≥500 copies /mL;
4. History of severe hypersensitivity reaction;
5. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, New York Heart Association Class II or greater congestive heart failure, atrial fibrillation, or other clinically significant cardiac disease within 12 months before enrollment;
6. History of organ transplant surgery;
7. Required systemic application of immunosuppressive or other drugs;
8. Auto-SCT within the 3 months before enrollment;
9. Active autoimmune or inflammatory diseases of the nervous system (e.g., Guillain-Barre syndrome (GBS), amyotrophic lateral sclerosis (ALS)) and clinically active cerebrovascular diseases (e.g., cerebral edema, posterior reversible encephalopathy syndrome (PRES));
10. Requirement for urgent therapy due to ongoing or impending oncologic emergency (eg, leukostasis or tumor lysis syndrome (TLS)) ;
11. Presence or suspicion of a fungal, bacterial, viral, or other infection that is uncontrolled or requiring antimicrobials for management;
12. Live vaccine received within the ≤ 4 weeks before enrollment;
13. Persons with serious mental illness;
14. History of major surgical operations four weeks before enrollment;
15. History of alcoholism or substance abuse;
16. Was identified by the investigators as unsuitable to participate in the study.

Where this trial is running

Xuzhou, Jiangsu

• Kailin Xu — Xuzhou, Jiangsu, China (Recruiting)

Study contacts

• Study coordinator: Kailin Xu, MD.,PD.

Conditions Acute Myeloid Leukemia Refractory; Acute Myeloid Leukemia, in Relapse