CD7 CAR-T Cells in T-cell Lymphoma/Leukemia

Study Overview
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Brief Summary
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T-cell lymphoma/leukemia is a group of highly lethal diseases with a high relapse rate and poor prognosis. CD7 was proved to be widely expressed in T-cell malignant, which makes it a promising therapeutic target. In this study we aim to test the safety and efficacy of CD7 CAR-T cells in T-cell lymphoma/leukemia.

Detailed Description
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T-cell lymphoma accounts for 10% 15% of non-Hodgkin lymphoma in China. According to the World Health Organization (WHO), T-cell lymphoma was divided into the following subtypes: T-cell, NK cell lymphoma/leukemia. There were two major categories: anterior T-cell tumors and posterior thymic T-cell lymphomas, which originate from lymph nodes, extranodal tissue, or skin; mature or peripheral T-cell lymphomas. Generally speaking, the relapse accounts for 50-60% after first-line treatment, while the remission rate with second-line treatment was extremely low. Collectively, there was an urgent need for new treatment modalities to improve the clinical outcomes of these patients. CD7 is a transmembrane glycoprotein that plays an important role in T-cell and T-cell/B-cell interactions during early lymphoid development. The expression of CD7 persist from stem to mature T cells. CD7 was proved to be widely expressed in T-cell malignant, which makes it a promising therapeutic target. In this study we aim to testify the safy and efficacy of CD7 CAR-T cells in T-cell lymphoma/leukemia.

Official Title
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Study of CD7 CAR-T Cells in Adult Refractory and Recurrent T-cell Lymphoma/Leukemia

Conditions
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T Lymphoblastic Leukemia/Lymphoma

Intervention / Treatment
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* Biological: CD7 CAR-T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-75 (≥ 18 years old, ≤ 75 years old), gender is not limited; The subject voluntarily participates in the research and signs the Informed Consent by himself or his legal guardian; According to the National Comprehensive Cancer Network (NCCN) T lymphocytic lymphoma (2020.V1)/acute lymphoblastic leukemia (2020. V1) practice guidelines, diagnosed with T-cell lymphoma; Meet the diagnostic criteria for relapsed/refractory T-cell lymphoma, including any of the following: 1) Failure to obtain CR at the end of induction therapy; 2) Patients who have obtained CR have blasts in peripheral blood or bone marrow (proportion >5%), or extramedullary diseases; 5. Have not received antibody therapy within 2 weeks before cell therapy; 6. ECOG score of 0-2; 7. The subject has no contraindications to peripheral apheresis; 8. Expected survival time of more than 3 months. Exclusion Criteria: Those who have a history of allergy to any of the ingredients in cell products; Laboratory tests for the following: including but not limited to, total serum bilirubin≧ 1.5mg/dl; Serum ALT or AST greater than 2.5 times the upper limit of normal; Blood creatinine≧ 2.0mg/dl; Platelet count≦ 10×109/L; Patients with cardiac insufficiency who belong to class III or IV according to the New York Cardiology Association (NYHA) cardiac function grading standards; or echocardiography with left ventricular ejection fraction (LVEF) < 50%; Abnormal lung function, blood oxygen saturation under indoor air < 92%; Myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other serious clinical heart disease within 12 months before enrollment; Grade 3 hypertension with poor control of blood pressure with medication; Patients with other advanced tumors (those who are assessed as stable after treatment of other tumors can be enrolled); Previous head trauma, impaired consciousness, epilepsy, more serious cerebral ischemia or cerebral hemorrhage disease; Known central nervous system leukemia (CNS2 or CNS3), resistance to intrathecal chemotherapy injections and/or ongoing head and/or spinal radiation therapy; Previous CNS history but has been effectively controlled to allow enrollment; Patients with autoimmune diseases, immunodeficiency or other patients requiring immunosuppressant therapy; presence of uncontrolled, active infection; Have previously used any CAR-T cell product or other genetically modified T cell therapy; Live vaccination within 4 weeks prior to enrollment; HIV, HBV, HCV and TPPA/RPR infections, and HBV carriers; Subject has a history of alcoholism, drug addiction or mental illness; The subject has participated in any other clinical research within 3 months before joining this clinical study; Female subjects have any of the following conditions: a) are pregnant/lactating; or b) have plans to become pregnant during the trial; or c) are of childbearing potential and unable to use effective contraception; There are other circumstances in which the investigator believes that the subject is not suitable for this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group<br>CD7 CAR-T treatment group | Biological: CD7 CAR-T cells<br>* patient was subjected to 0.5-2×10^6 cells/kg of CD7 CAR- T<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TEAEs | Adverse events during treatment | From date of initial treatment to the 30 days after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall response rate | the proportion of complete and partial response patients | baseline and 8 weeks, up to 1 year |