4SCAR-CD44v6 T Cell Therapy Targeting Cancer

Multi-center Phase I/II Clinical Trial of 4SCAR-CD44v6 T Cells for Treating Cancer

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.

Study Overview

• Status: Recruiting
• Conditions: Cancers Which Are CD44v6 Positive
• Intervention / Treatment: Biological: CD44v6-specific CAR gene-engineered T cells

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.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518000
      • Recruiting
      • Shenzhen Geno-Immune Medical Institute
    • Shenzhen, Guangdong, China, 518000
      • Recruiting
      • Shenzhen Children's Hospital
      • Contact: Xiuli Yuan, MD; Phone Number: 86-18938690212; Email: 18938690212@163.com
    • Shenzhen, Guangdong, China, 518101
      • Recruiting
      • Shenzhen Hospital of Southern Medical University
      • Contact: Jie Mao, MD; Phone Number: 86-0755-233; Email: myw921@163.com
    • Shenzhen, Guangdong, China, 518107
      • Recruiting
      • The Seventh Affilliated Hospital, Sun Yat-Sen University

Participation Criteria

Eligibility Criteria

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

Description

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.

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: Experimental: Single arm 4SCAR-CD44v6 T cells to treat cancer	Biological: CD44v6-specific CAR gene-engineered T cells; 4SCAR-CD44v6 Infusion of 4SCAR-CD44v6 T cells at 10^6 cells/kg body weight

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
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
• Collaborators: The Seventh Affiliated Hospital of Sun Yat-sen University; Shenzhen Children's Hospital; Shenzhen Hospital of Southern Medical University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Anticipated): May 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: June 9, 2020
• First Submitted That Met QC Criteria: June 9, 2020
• First Posted (Actual): June 11, 2020

Study Record Updates

• Last Update Posted (Actual): June 11, 2020
• Last Update Submitted That Met QC Criteria: June 9, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: CAR-T; Gastric cancer; Lymphoma; Breast cancer; CD44v6
• Other Study ID Numbers: GIMI-IRB-20004

Drug and device information, study documents

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