LILRA6 CAR-T therapy for relapsed or refractory acute myeloid leukemia.

Dose Escalation and Expansion Clinical Study of Targeted LILRA6 CAR-T for the Treatment of Relapsed/Refractory Acute Myeloid Leukemia

This trial will test LILRA6-directed CAR-T cell therapy to see if it helps adults (18–75) whose acute myeloid leukemia has returned or not responded to prior treatments.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 48 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, CAR-T, chimeric antigen receptor
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT07263906 on ClinicalTrials.gov

What this trial studies

This single-center, open-label, single-arm Phase I study delivers LILRA6-directed CAR-T cells by intravenous infusion to adults with relapsed or refractory AML that express LILRA6. The dose-escalation phase uses a conventional 3+3 design to identify a safe and tolerable dose, with at least 28 days of close safety monitoring and up to two years of follow-up for each patient. After a recommended dose is selected based on safety, persistence, and preliminary efficacy, an approximately 30-patient dose-expansion cohort will further evaluate safety and anti-leukemia activity. All treated patients will continue long-term follow-up for up to two years post-infusion.

Who should consider this trial

Good fit: Adults aged 18–75 with relapsed or refractory AML that expresses LILRA6, who meet organ-function and other eligibility criteria and can travel to the study site, are the intended candidates.

Not a fit: Patients whose leukemia lacks LILRA6 expression, or who are too frail or have uncontrolled infections or severe organ dysfunction, are unlikely to benefit.

Why it matters

Potential benefit: If successful, the therapy could produce deeper or longer remissions for patients whose AML has failed standard treatments.

How similar studies have performed: CAR-T therapies for AML have shown only limited and early successes and substantial risks to date, and targeting LILRA6 is a novel and largely untested approach.

Eligibility criteria

Inclusion Criteria:

1. Voluntarily participate in this study and sign the informed consent form.
2. Age range: 18 - 75 years old. Gender is not restricted.
3. Refractory/Recurrent AML: Meeting any one of the following criteria for refractory or recurrent cases is sufficient. 1) Refractory: (1) In the case of a newly diagnosed patient, treatment with the standard regimen for two courses fails to achieve complete remission (CR); (2) Recurrence within 12 months after consolidation and intensification therapy following CR; (3) Recurrence after 12 months with no response to salvage chemotherapy; (4) ≥ 2 recurrences; (5) Persistent extramedullary leukemia; 2) Recurrence: (1) Leukemia cells reappear in the peripheral blood after complete remission (CR) of AML; (2) The percentage of blasts in the bone marrow is ≥ 5% (excluding other reasons such as bone marrow regeneration after consolidation chemotherapy); (3) Infiltration of leukemia cells in sites other than the bone marrow (excluding the central nervous system).
4. Expected survival period ≥ 12 weeks.
5. The positive rate of LILRA6 expression in bone marrow/tumor cells is ≥ 20%
6. ECOG score ranging from 0 to 2 points.
7. Sufficient organ function reserve: Alanine aminotransferase and Aspartate aminotransferase ≤ 2.5× UNL (upper limit of normal value); Creatinine clearance rate (Cockcroft-Gault method) ≥ 45 mL/min; Serum total bilirubin ≤ 1.5× UNL; Ejection fraction of the heart (EF) ≥ 45%; In an indoor natural air environment, baseline oxygen saturation \> 92%; Blood routine: All of the following criteria are met: Absolute number of neutrophils ≥ 0.5×10\^9 /L, Platelet count ≥ 30×10\^9 /L, Hemoglobin ≥ 7.0 g/dl.
8. Allow those who have previously undergone a single autologous hematopoietic stem cell transplantationAllowing previous recipients of a single autologous hematopoietic stem cell transplantation.
9. Pregnancy tests for the female subjects of childbearing age must be negative, and they must also agree to take effective contraceptive measures during the trial.
10. There are no uncontrollable infectious activities (including lung infections).
11. Distance from the last anti-tumor treatment: Systemic chemotherapy / systemic radiotherapy / immunotherapy ≥ 3 weeks, targeted drug elution period ≥ 2 weeks.
12. No active infection of the novel coronavirus or influenza.

Exclusion Criteria:

1. Those who have a severe history of allergic reaction to any component of the cell preparation or the pre-treatment chemotherapy drugs.
2. Those with a history of other active malignant tumors.
3. There are active infections that require treatment (excluding simple urinary tract infections and bacterial pharyngitis); the use of prophylactic antibiotics, antiviral drugs, and antifungal drugs is permitted.
4. Active hepatitis B (with HBsAg positive and HBV-DNA ≥ 10³ copies/mL), hepatitis C infection, syphilis, or other acquired/innate immune deficiency disorders (including HIV infection).
5. According to the New York Heart Association (NYHA) classification of cardiac function, those with cardiac function at grade III or IV.
6. Previous anti-tumor treatment-related toxic reactions have not yet recovered to a grade ≤ 1 (according to CTCAE 5.0), except for fatigue, anorexia and hair loss.
7. Those with a history of epilepsy or other central nervous system diseases that may affect the research assessment.

8: Those who have received any other targeted LILRA6 drug treatment before. 9.Breastfeeding women who do not wish to stop breastfeeding. 10.The researchers believe that there may be any other circumstances that could increase the risks for the subjects or interfere with the test results.

Where this trial is running

Hangzhou, Zhejiang

• The Second Affiliated Hospital,School of Medicine,Zhejiang University — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: Wenbin Qian, Professor

Conditions Refractory Acute Myeloid Leukemia; Recurrent Acute Myeloid Leukemia; Refractory/recurrent acute myeloid leukemia; LILRA6 CAR-T; Acute myeloid leukemia