Clinical trial NCT04427449: 4SCAR-CD44v6 T Cell Therapy Targeting Cancer
Official title: Multi-center Phase I/II Clinical Trial of 4SCAR-CD44v6 T Cells for Treating Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Cancers Which Are CD44v6 Positive
Keywords: CAR-T
CD44v6
Breast cancer
Gastric cancer
Lymphoma
Lead sponsor: Shenzhen Geno-Immune Medical Institute
Sponsor class: OTHER
Collaborators: name: Shenzhen Hospital of Southern Medical University
name: The Seventh Affiliated Hospital of Sun Yat-sen University
name: Shenzhen Children's Hospital
First posted: 2020-06-11
Enrollment: 100
Sex: ALL
Minimum age (years): 6
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 4SCAR-CD44v6 T-cell therapy targeting multiple cancers. The study also aims to learn more about the function of the CD44v6 CAR-T cells and their persistency in the patients.

Detailed description: CD44 variant domain 6 (CD44v6) which belongs to CD44 family has been implicated in tumorigenesis, tumor cell invasion and metastasis. The expression of CD44v6 was reported for the majority of squamous cell carcinomas, a proportion of adenocarcinomas of differing origin, a proportion of melanoma and lymphoma. This expression pattern has made CD44v6 an attractive target for the therapy of various types of CD44v6 positive cancers.

The T cells from patients or transplantation donors will be genetically modified with lentiviral CAR vector to recognize specific molecules - CD44v6 expressed on the surface of the cancer 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 CD44v6 CAR-T cell therapy in multiple cancers including - but not limited to - stomach cancer, breast cancer, prostate cancer, multiple myeloma and lymphoma which are CD44v6 positive. Another goal of the study is to learn more about the function of the 4SCAR-CD44v6 T cells and their persistency in the patients.

Eligibility criteria: Inclusion Criteria:

1. Age older than 6 months.
2. Confirmed expression of CD44v6 in tumor specimens by immuno-histochemical staining or flow cytometry.
3. Karnofsky performance status (KPS) score is higher than 70 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. Receive treatment related to CD44v6 targeted therapy.
7. Patients, in the opinion of investigators, may not be able to comply with the study.

Primary outcomes:
measure: Safety of infusion
timeFrame: 1 year
measure: Clinical response
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Shenzhen
country: China
facility: Shenzhen Children's Hospital
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen Geno-immune Medical Institute
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen Hospital of Southern Medical University
state: Guangdong
city: Shenzhen
country: China
facility: The Seventh Affilliated Hospital, Sun Yat-Sen University
state: Guangdong
Study officials:
References: