Anti-ILT3 CAR-T therapy for relapsed or refractory acute myeloid leukemia

Clinical Study of Autologous T Cells Modified With ILT3 Chimeric Antigen Receptor for Relapsed/Refractory Acute Myeloid Leukemia (M4/M5)

This study is testing a new CAR-T cell therapy to see if it can help people with relapsed or hard-to-treat acute myeloid leukemia feel better and improve their chances of recovery.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Carbiogene Therapeutics Co. Ltd. (Industry-sponsored)
• Drugs / interventions: chemotherapy, CAR-T, CAR T
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT04803929 on ClinicalTrials.gov

What this trial studies

This pilot study evaluates the safety and efficacy of a novel anti-ILT3 CAR-T cell therapy specifically designed for patients with relapsed or refractory acute myeloid leukemia (M4/M5). A total of 25 participants will receive intravenous administration of anti-ILT3 CAR-T cells, with dosages determined through a '3+3' dose escalation approach. The study aims to assess how well this targeted therapy can improve outcomes for patients who have not responded to standard treatments.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 70 with relapsed or refractory AML M4/M5 confirmed by specific diagnostic criteria.

Not a fit: Patients with AML subtypes other than M4/M5 or those who do not meet the eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for patients with difficult-to-treat forms of acute myeloid leukemia.

How similar studies have performed: While CAR-T therapies have shown promise in other hematological malignancies, this specific approach targeting ILT3 is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

1. Male or female patients, aged ≥18 years or ≤70 years;
2. Acute myeloid leukemia AML M4/M5 subtype was diagnosed according to Fab standard classification, confirmed by bone marrow IHC or ILT3-positive expression by flow cytometry in monocytes (primary and young monocytes in bone marrow ≥20%)
3. Relapsed/refractory patients, whose conditions meet:

   * Recurrent AML diagnosis standard: complete remission (CR) after the original cells in peripheral blood again leukemia cells or bone marrow \> 0.050 (with the exception of consolidation chemotherapy after bone marrow regeneration for other reasons) or myeloid leukemia cells infiltrating outside.
   * Refractory AML diagnostic criteria: after two standard regimen for treatment invalid early cure; patients who relapsed within 12 months after consolidation and intensive treatment after CR; relapsed after 12 months but failed to respond to conventional chemotherapy; 2 or more recurrences; patients with persistent extramedullary leukemia.
4. Main organ functions meet the following conditions:

   * Kidney function: creatinine clearance (absolute value) or 60 ml/min or creatinine \< 2.0 mg/dl or \< 2 times the subjects' age group upper limit of normal (ULN) blood.
   * Liver function: ALT ≤ 3 or less ULN, AST ≤ 3 or less ULN.
   * Heart function: the ejection fraction ≥ 50%, measured by echocardiography (ECHO) or more acquisition scan (MUGA).
   * Lung function: no clinical significance of pleural effusion, baseline blood oxygen saturation \> 92%.
5. ECOG physical status score 0-3.
6. No use of steroid hormones within 2 weeks.
7. Sufficient venous access to single or venous blood collection is available, and there are no other contraindications to blood cell separation.
8. Signed written informed consent form.

Exclusion Criteria:

Subjects will not be included in the study if they meet any of the following criteria:

1. Pregnant or lactating women;
2. HIV serological positive;
3. Active bacterial, fungal or viral infections that are not controlled by treatment;
4. Suffer from coronary heart disease, angina pectoris, myocardial infarction, arrhythmia, cerebral thrombosis, cerebral hemorrhage or other serious cardiovascular and cerebrovascular diseases;
5. History and concomitant diseases:

   * Subjects with known or suspected autoimmune diseases or immunodeficiency diseases;
   * Subjects requiring systemic treatment with corticosteroids or other immunosuppressive agents during treatment;
   * Subjects who have previously received other gene therapies;
   * Subjects with a history of organ transplantation (referring to solid organ transplantation);
   * Subjects with severe mental disorders;
   * Participated in other clinical studies within one month before the collection of PBMC;
   * Uncontrolled active hepatitis B and/or C infection (hepatitis B: HBV DNA \> 500 IU/ml or copy number \> 2500 copies /ml;
   * Hepatitis C: HCV antibody positive and HCV-RNA levels above the detection limit);
   * Any serious or uncontrolled disease that the Investigator considers to be likely to increase the risk associated with study participation, study drug administration, or affect the subject's ability to receive the study drug;
   * Subjects who underwent major surgery or suffered significant trauma within 4 weeks prior to the collection of PBMCs, or who are expected to require major surgery during the study period.

Where this trial is running

Hangzhou, Zhejiang

• Zhejiang Provincal People's Hospital — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Principal investigator: Jianping Lan — Zhejiang Provincial People's Hospital
• Study coordinator: Lai Jin

Conditions AML M4; AML M5