Anti-CD7 CAR-T Cell Therapy for Relapse and Refractory CD7 Positive T Cell Malignancies

Phase 1

Recruiting

• Conditions: Peripheral T Cell Lymphoma; T Lymphoblastic Leukemia/Lymphoma; T-cell Acute Lymphoblastic Leukemia; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma
• Interventions: Drug: anti-CD7 CAR-T cells

• Registration Number: NCT05290155
• Lead Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of CAR T cell treatment targeting CD7 in patients with relapsed or refractory CD7 positive T-cell hematological maliganacies

Detailed Description

This study is single-armed，open lable，dose escalation clinical trial.The main purpose is to evaluate the safety and efficacy of anti-CD7 CAR-T cells in relapsed/refractory patients with CD7 positive T cell malignancies,including T lymphoblastic lymphoma/leukemia ,T-cell non-Hodgkin lymphoma(peripheral T cell lymphoma,NOS,angioimmunoblastic T cell lymphoma and anaplastic large cell lymphoma).There will be three CAR T cell dose groups:0.5\*10\^6 cells per kilogram of body weight;1\*10\^6 cells per kilogram of body weight，2 \*10\^6 ells per kilogram of body weight.

Study Timeline

• Study First Submitted: 2022-03-09
• Study First Submitted QC: 2022-03-18
• Study First Posted: 2022-03-22
• Study Start: 2022-05-04
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-26
• Last Update Posted: 2023-11-28
• Primary Completion: 2024-08-01
• Study Completion: 2024-11-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 4

Inclusion Criteria

Not provided

Exclusion Criteria

1. Malignant tumors other than T cell malignancies within 5 years prior to screening, in addition to adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, localized prostate cancer after radical resection, and ductal carcinoma in situ after radical resection;
2. Uncontrolled infection including bacteral or virus or fugal disease;patients with positive HBsAg or HBcAb and positive peripheral blood HBV DNA titer detection ;HCV antibody positive and peripheral blood HCV RNA positive; HIV antibody positive; syphilis positive;
3. Any instability of systemic disease, including but not limited to unstable angina, cerebrovascular accident, or transient cerebral ischemic (within 6 months prior to screening),myocardial infarction (within 6 months prior to screening), congestive heart failure (New York heart association (NYHA) classification ≥ III), need drug therapy of severe arrhythmia,liver, kidney, or metabolic disease;
4. Any uncontrolled disease may affect entry
5. Current or history of CNS involvement by malignancy.Known history or presence of clinically relevant central nervous system (CNS) pathology.Patients with a known history or prior diagnosis other immunologic or inflammatory disease affecting the CNS (such as epilepsy)
6. Patients who are receiving systemic steroid treatment and requiring long-term systemic steroid treatment during the treatment as determined by the investigator before screening (except inhalation or topical use); And subjects treated with systemic steroids (except inhalation or topical use) within 72h prior to cell transfusion;
7. Subjects treated with anti-PD1 or anti-PDL1 therapies within 3months before enrollment
8. Pregnant or lactating woman, and female subject who plans to have a pregnancy within 1 year after cell transfusion, or male subject whose partner plans to have a pr egnancy within 1 year after cell transfusion;
9. Active or uncontrollable infection requiring systemic therapy Received CAR-T treatment or other gene therapies before enrollment;
10. Kown be allergic to anti-TRBC1 CAR-T cells or drugs(Fludarabine or Cyclophophamide)
11. The investigators consider other conditions unsuitable for enrollment.
12. Patients who may not be able to sign the Informed Consent due to disease,or who do not understand or unwillingness or inability to comply with research requirements

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Anti-CD7 CAR T cells	anti-CD7 CAR-T cells	Administration with anti-CD7 CAR-T cells in the relapsed/refractory T cell hematological malignancy patients

Primary Outcome Measures

Name	Time	Method
Incidence of Treatment-Emergent Adverse Events	28 days post infusion	The occurence of study related adverse effects defined by NCI CTCAE5.0

Secondary Outcome Measures

Name	Time	Method
Duration of remission (DOR) after administration	2 years post infusion	Duration of remission (DOR) after administration
CAR-T cell persistence	2 years post infusion	Using flow cytometry to reveal cell surface expression of the CAR protein on T cells;and using quantitative polymerase chain reaction to detect DNA copies of the transgene irrespective of gene expression(per ug DNA) to evaluate anti-CD7 CAR-T cell persistence after infusion
Number of CD7+ lymphocytes of peripheral blood	2 years post infusion	To evaluate CD7 positive cells of peripheral blood after infusion
Total response rate (ORR) after administration	3 months post infusion	CR+CRi for T-ALL ;CR+PR for T cell lyphoma and T lymphoblastic lymphoma
CAR-T cell expansion	2 years post infusion	Using flow cytometry to reveal cell surface expression of the CAR protein on T cells;and using quantitative polymerase chain reaction to detect DNA copies of the transgene irrespective of gene expression(per ug DNA) to evaluate anti-CD7 CAR-T cell expansion after infusion
Overall survival(OS) after administration	2 years post infusion	Overall Survival (OS)after administration
Progression Free Survival (PFS) after administration	2 years post infusion	Progression Free Survival (PFS) after administration

Trial Locations

Locations (1)

Xianmin General Song; 🇨🇳 Shanghai, China