Multi-CAR T Cell Therapy for Acute Myeloid Leukemia

Official title

Multi-center Phase I/II Clinical Trial of Multi-CAR T Cell Therapy for Acute Myeloid Leukemia

Overview

The purpose of this clinical trial is to assess the feasibility, safety and efficacy of multi-CAR T cell therapy targeting different AML surface antigens in patients with relapsed or refractory acute myeloid leukemia (AML). Another goal of the study is to learn more about the function of the multi-CAR T cells and their persistency in the patients.

Detailed description

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

In this study, the patients' own T cells will be genetically modified with lentiviral vectors expressing chimeric antigen receptors. The multi-CAR T cells recognize specific molecules such as CD33, CD38, CD123, CD56, MucI, and CLL1, which are often found expressed on the surface of AML cells. The engineered CAR T cells will be infused into patients.

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

Interventions

• Biological Muc1/CLL1/CD33/CD38/CD56/CD123-specific gene-engineered T cells
  Infusion of Muc1/CLL1/CD33/CD38/CD56/CD123-specific gene-engineered T cells

Primary outcome measures

• percentage of patients with treatment related adverse effect [Time frame: a year]

Secondary outcome measures (1)

• Anti tumor activity of fourth generation CAR-T cells in patients with relapsed or refractory AML [Time frame: a year]

Eligibility criteria

Inclusion criteria

• Age older than 2 years.
• CD33, CD38, CD56, CD123, MucI, and CLL1 expression can be identified in the malignant cells by immuno-histochemical staining or flow cytometry.
• Karnofsky performance status (KPS) score is higher than 80 and life expectancy > 2 months.
• 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.
• Hgb≥80g/L.
• No cell separation contraindications.
• Abilities to understand and the willingness to provide written informed consent.

Exclusion criteria

• Sever illness or medical condition, which would not permit the patient to be managed according to the protocol, including active uncontrolled infection.
• Active bacterial, fungal or viral infection not controlled by adequate treatment.
• Known HIV or hepatitis B virus (HBV) infection.
• Pregnant or nursing women may not participate.
• History of glucocorticoid for systemic therapy within the week prior to entering the test.
• Previously treatment with any gene therapy products.
• Patients, in the opinion of investigators, may not be eligible or not able to comply with the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Shenzhen Geno-immune Medical Institute — Shenzhen

Publications

• Pei K, Xu H, Wang P, Gan W, Hu Z, Su X, Zhang H, He Y. Anti-CLL1-based CAR T-cells with 4-1-BB or CD28/CD27 stimulatory domains in treating childhood refractory/relapsed acute myeloid leukemia. Cancer Med. 2023 Apr;12(8):9655-9661. doi: 10.1002/cam4.5916. Epub 2023 Apr 9. PMID 37031462

Identifiers

NCT: NCT03222674 · GIMI-IRB-17015

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗