Combination CAR-T therapy targeting AML using CLL-1 plus CD123 or CD33

Multi-center Phase I/II Clinical Trial of Multiple CAR T Cells for Treating Acute Myeloid Leukemia

This trial will test whether giving people with relapsed or refractory AML a mix of CAR‑T cells that target CLL‑1 together with CD123 or CD33 is safe and can help control their leukemia.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 6 Months to 75 Years
• Sex: All
• Sponsor: Shenzhen Geno-Immune Medical Institute (Academic / other)
• Drugs / interventions: CAR T, CAR-T
• Locations: 1 site (Shenzhen, Guangdong)
• Trial ID: NCT04010877 on ClinicalTrials.gov

What this trial studies

This phase 1/2 trial engineers patients' (or donor) T cells with lentiviral CAR constructs directed at CLL‑1 and at CD123 or CD33, then delivers the modified cells intravenously. The study enrolls people with relapsed or refractory acute myeloid leukemia whose blasts express one or more of the target antigens. Primary goals are to determine feasibility and safety and to gather early evidence of anti‑leukemia activity and CAR‑T cell persistence. Investigators will monitor patients for response, side effects, and how long the engineered T cells remain detectable.

Who should consider this trial

Good fit: People (age >6 months) with relapsed or refractory AML whose blasts express CLL‑1 and/or CD123 or CD33, who have good performance status and adequate organ function, and who can provide informed consent are the intended candidates.

Not a fit: Patients whose leukemia lacks the target antigens, or who have uncontrolled infection, severe comorbidities, poor organ function, or do not meet performance criteria are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the combination approach could deepen remissions and reduce relapse by targeting both bulk leukemia and leukemia stem cells while addressing antigen escape.

How similar studies have performed: CD33 and CD123 CAR‑T approaches have shown AML clearance in preclinical work and some early clinical reports, but relapse from antigen escape remains a problem, and combining CLL‑1 with these targets is a newer, less tested strategy.

Eligibility criteria

Inclusion Criteria:

1. Age older than 6 months.
2. Confirmed expression of CLL-1, CD123 and/or CD33 in blast AML by immuno-histochemical staining or flow cytometry.
3. Karnofsky performance status (KPS) score is higher than 80 and life expectancy \> 3 months.
4. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements: cardiac ejection fraction ≥ 50%, oxygen saturation ≥ 90%, creatinine ≤ 2.5 × upper limit of normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal, total bilirubin ≤ 2.0mg/dL.
5. Hgb≥80g/L.
6. No cell separation contraindications.
7. Abilities to understand and the willingness to provide written informed consent.

Exclusion Criteria:

1. Sever illness or medical condition, which would not permit the patient to be managed according to the protocol, including active uncontrolled infection.
2. Active bacterial, fungal or viral infection not controlled by adequate treatment.
3. Known HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
4. Pregnant or nursing women may not participate.
5. Use of glucocorticoid for systemic therapy within one week prior to entering the trial.
6. Previous treatment with any gene therapy products.
7. Patients, in the opinion of investigators, may not be able to comply with the study.

Where this trial is running

Shenzhen, Guangdong

• Shenzhen Geno-immune Medical Institute — Shenzhen, Guangdong, China (Recruiting)

Study contacts

• Principal investigator: Lung-Ji Chang, Ph.D — Shenzhen Geno-Immune Medical Institute
• Study coordinator: Lung-Ji Chang, Ph.D

Conditions Acute Myeloid Leukemia; AML; CAR T; CD33, CD123, CLL-1