Universal 4SCAR7U Targeting CD7-positive Malignancies

• ClinicalTrials.gov Identifier: NCT05995028
• Recruitment Status: Recruiting
• First Posted: August 16, 2023
• Last Update Posted: October 12, 2023
• Sponsor: Shenzhen Geno-Immune Medical Institute
• Information provided by (Responsible Party): Shenzhen Geno-Immune Medical Institute

Tracking Information

• First Submitted Date: August 8, 2023
• First Posted Date: August 16, 2023
• Last Update Posted Date: October 12, 2023
• Estimated Study Start Date: October 31, 2023
• Estimated Primary Completion Date: September 30, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 8, 2023)

Safety of infusion [ Time Frame: 6 months ]

Treatment-related adverse events are assessed by NCI CTCAE V4.0 criteria.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 8, 2023)

Clinical response [ Time Frame: 1 year ]

Objective responses (complete response (CR) + partial response (PR)) are assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Universal 4SCAR7U Targeting CD7-positive Malignancies
• Official Title: Safety and Efficacy of Universal 4SCAR7U T Cell Therapy Targeting CD7-positive Hematological Malignancies
• Brief Summary: The purpose of this clinical trial is to assess the feasibility, safety and efficacy of universal CAR T cells based on 4SCAR7U design against CD7-positive hematological malignancies using CD7 specific universal CAR T cells. The study also aims to learn more about the function of CD7 targeting CAR T cells and their persistence in patients of hematological malignancies.

Detailed Description

Hematological malignancies including B-, T-cell acute lymphoblastic leukemia (B-ALL, T-ALL), B and T cell lymphoma (BCL, TCL), natural killer cell lymphoma (NKL) and acute myeloid leukemia (AML) are aggressive diseases which may express the early T cell development molecule CD7.T-ALL represents 15% of childhood and 25% of adult ALL, and T-ALL patients are prone to early disease relapse and suffer from poor treatment outcomes. According to European Group for the Immunological Characterization of Leukemias (EGIL), the presence of cytoplasmic or membrane expression of CD3 defines T-ALL. Several immunophenotypic classifications have been proposed: (TI) the immature subgroup or pro-T-ALL is defined by the expression of CD7 and cCD3; (TII) pre-T-ALL also expresses CD2 and/or CD5 and/or CD8; (TIII) or cortical T-ALL shows CD1a positivity; and (TIV), mature T-ALL is characterized by the presence of surface CD3 and CD1a negativity.Over the past few years, T cells modified with lentiviral chimeric antigen receptor (CAR) gene have been studied in different clinical settings. CD7 is a T cell surface molecule that plays important role in T cell and B cell interaction in early lymphoid development, displays membrane expression early during T cell development before TCR rearrangement, and persists through terminal stages of T cell development, and has been a well-known marker for T-ALL. CD7 is considered a promising target for the treatment of T-ALL, TCL, AML and NKL. In this study, the study proposes to investigate an universal CD7 targeting CAR-T design, 4SCAR7U in combination with alternative targeting CAR-T cells as a new strategy to treat CD7-positive hematological malignancies.

The 4SCAR7U T cells are genetically engineered and manufactured in bulk amount that can be supplied off-the-shelf without being custom made from individual patients. The immediate availability of the CAR-T cells makes clinical treatment convenient and timely for rapid progressing disease or for highly immune suppressed patients. This application can be time- and cost-effective. This novel approach may also overcome problems of functionally defective autologous T cells. The purpose of this clinical trial is to assess the feasibility, safety and efficacy of the 4SCAR7U T cell product in hematological malignancies. Another goal of the study is to learn more about the function of this novel product and its persistence in the patients.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• T-cell Acute Lymphoblastic Leukemia
• T-cell Acute Lymphoblastic Lymphoma
• Acute Myeloid Leukemia
• NK Cell Lymphoma

Intervention

Biological: Universal CD7-specific CAR gene-engineered T cells

Infusion of 4SCAR7U T cells

Study Arms

Experimental: Universal 4SCAR7U cells to treat CD7-positive hematological malignancies

Intervention: Biological: Universal CD7-specific CAR gene-engineered T cells

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 8, 2023): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2026
• Estimated Primary Completion Date: September 30, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Age older than 6 months.
2. Confirmed expression of CD7 and additional surface antigens in the cancer cells 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 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Months to 75 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Lung-Ji Chang, Ph.D; 86-136 7112 1909; c@szgimi.org

Contact: Ying Deng; 86-0755-8672 5195; c@szgimi.org

• Listed Location Countries: China

Administrative Information

• NCT Number: NCT05995028
• Other Study ID Numbers: GIMI-IRB-23002
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Shenzhen Geno-Immune Medical Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: Shenzhen Geno-Immune Medical Institute
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Shenzhen Geno-Immune Medical Institute
• Verification Date: October 2023