Clinical trial NCT03222674: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Acute Myeloid Leukemia
Keywords: AML
CAR T
Muc1,CLL1, CD33, CD38, CD56, and/or CD123
Lead sponsor: Shenzhen Geno-Immune Medical Institute
Sponsor class: OTHER
Collaborators: name: Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
name: Yunnan Cancer Hospital
First posted: 2017-07-19
Enrollment: 10
Sex: ALL
Minimum age (years): 2
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Eligibility criteria: Inclusion Criteria:

1. Age older than 2 years.
2. CD33, CD38, CD56, CD123, MucI, and CLL1 expression can be identified in the malignant cells by immuno-histochemical staining or flow cytometry.
3. Karnofsky performance status (KPS) score is higher than 80 and life expectancy \> 2 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 or hepatitis B virus (HBV) infection.
4. Pregnant or nursing women may not participate.
5. History of glucocorticoid for systemic therapy within the week prior to entering the test.
6. Previously treatment with any gene therapy products.
7. Patients, in the opinion of investigators, may not be eligible or not able to comply with the study.

Primary outcomes:
measure: percentage of patients with treatment related adverse effect
timeFrame: a year
Secondary outcomes:
measure: Anti tumor activity of fourth generation CAR-T cells in patients with relapsed or refractory AML
timeFrame: a year
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Zhujiang Hospital of Southern Medical University
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen Geno-immune Medical Institute
state: Guangdong
city: KunMing
country: China
facility: Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center
state: Yunnan
Study officials:
affiliation: Shenzhen Geno-Immune Medical Institute
name: Lung-Ji Chang
role: PRINCIPAL_INVESTIGATOR
References: