Multiple CAR-T Cell Therapy Targeting AML

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

The purpose of this clinical trial is to assess the feasibility, safety and efficacy of multiple CAR T-cell therapy which combines CAR T cells against CLL-1 with CAR T cells targeting CD123 or CD33 in patients with relapsed and refractory AML. The study also aims to learn more about the function of CAR T cells and their persistency in AML patients.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Biological: CLL-1, CD33 and/or CD123-specific CAR gene-engineered T cells

Detailed Description

Acute myeloid leukemia (AML) is a malignant disease characterized by the rapid growth of myeloblasts that grow in the bone marrow and interfere with the generation of normal blood cells.

Over the past few years, several groups have demonstrated that CD33 and CD123 CAR T cells can eradicate AML in both preclinical and clinical trials. Nevertheless, relapse after CAR T therapy remains a critical problem in treating AML. Disease relapse can be caused by antigen escape and by the outgrowth of residual leukemia stem cells (LSCs) that are not effectively eliminated by CAR T cells. CLL-1 (C-type lectin-like molecule-1) is a transmembrane glycoprotein, which is overexpressed in LSCs but absent in HSCs (hematopoietic stem cells), suggesting that CLL-1 might be a promising target for novel AML therapy. In this study, we use CLL-1 CAR-T in combination with CD123 and/or CD33 CAR-T as a new strategy to address LSC issue and prevent relapse caused by antigen escape.

The T cells from patients or transplantation donors will be genetically modified with lentiviral CAR vector to recognize specific molecules (CD33, CD123 or CLL-1) expressed on the surface of AML cells. The engineered T cells will be applied to patients through intravenous delivery.

The purpose of this clinical trial is to assess the feasibility, safety and efficacy of multiple CAR-T cell therapy in AML. Another goal of the study is to learn more about the function of CAR T cells and their persistency in the patients.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Lung-Ji Chang, Ph.D; Phone Number: 86-075586725195; Email: c@szgimi.org

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518000
      • Recruiting
      • Shenzhen Geno-immune Medical Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Multiple CAR T cells to treat AML	Biological: CLL-1, CD33 and/or CD123-specific CAR gene-engineered T cells; Infusion of CLL-1, CD33 and/or CD123-specific CAR-T cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of infusion	Treatment-related adverse events are assessed by NCI CTCAE V4.0 criteria.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical response	Objective responses (complete response (CR) + partial response (PR)) are assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.	1 year

Collaborators and Investigators

• Sponsor: Shenzhen Geno-Immune Medical Institute
• Investigators: Principal Investigator: Lung-Ji Chang, Ph.D, Shenzhen Geno-immune Medical Institute

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2025
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: July 4, 2019
• First Submitted That Met QC Criteria: July 4, 2019
• First Posted (Actual): July 8, 2019

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: AML; CAR T; CD33, CD123, CLL-1
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute
• Other Study ID Numbers: GIMI-IRB-19004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No