Chimeric Antigen Receptor T-Cell (CAR-T) Cells in Patients With R/R T-LBL

Study Overview
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Brief Summary
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This is a single center, single arm, open-lable phase I study to determine the safety and efficacy of T cells expressing CD7 chimeric antigen receptors (referred to as BT-007 CAR-T cells) in patients with relapsed or refractory acute T cell lymphoblastic lymphoma (R/R T-LBL).

Detailed Description
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Primary objective: To investigate the safety and efficacy of CD7 CAR-T cells in the treatment of patients with relapsed or refractory acute T cell lymphoblastic lymphoma (R/R T-LBL). Secondary objective: To assess the patient's quality of life after receiving the treatment.

Official Title
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Safety and Efficacy of BT-007 CAR-T Cells in the Treatment of Patients With Relapsed/Refractory T Cell Lymphoblastic Lymphoma (R/R T-LBL)

Conditions
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T Cell Lymphoblastic Lymphoma

Intervention / Treatment
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* Biological: BT-007 CD7 CAR-T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with CD7 positive T-cell lymphoma confirmed by histology; Relapsed refractory patients who received at least one line of systemic chemotherapy in the past; At least one measurable target lesion; Age: 18-70 years old (including 18 and 70 years old); The expected survival period is more than 3 months; Eastern Cooperative Oncology Group (ECOG) score 0-1; Important organ functions met: left ventricular ejection fraction≥50% according to cardiac ultrasound; Serum Cr≤1.25 times the upper limit of normal range (ULN) or endogenous creatinine clearance≥45mL/min (Cockcroft Gault formula); ALT and AST≤3 times ULN, TBIL≤1.5 times ULN; Blood routine: hemoglobin (Hgb)≥80g/L, neutrophil count (ANC)≥1×10^9/L, platelet PLT≥50×10^9/L； Coagulation function: International standardized ratio (INR)≤1.5 times ULN; Activated partial thromboplastin time (APTT)≤1.5 times ULN (unless the subject is receiving anticoagulant treatment, and prothrombin time (PT)/INR and APTT are within the expected range of anticoagulant treatment at the time of screening); The pregnancy test of women of childbearing age must be negative; Both male and female patients need to agree to use effective contraceptive measures during the treatment period and within the following 1 year; Participate in this test voluntarily and sign the informed consent. Exclusion Criteria: Used immunosuppressive agents or therapeutic doses of corticosteroids (defined as prednisone>20mg or equivalent dose) within one week before blood collection, or used drugs that stimulate bone marrow hematopoiesis, such as Human Granulocyte Colony Stimulating Factor (G-CSF); But physiological substitution, topical or inhaled steroids are permitted; Uncontrolled systemic active fungi, bacteria, viruses or other infections; Active hepatitis B (HBV DNA>500IU/mL), hepatitis C (HCV RNA positive) or human immunodeficiency virus (HIV) antibody positive; Central nervous system invasion, or central nervous system disease history, such as epilepsy, cerebrovascular disease, etc; Pregnant or lactating women, or patients do not agree to use effective contraceptives during treatment and within the following 1 year; Receiving allogeneic hematopoietic stem cell transplantation or organ transplantation; Previous history of other malignant tumors. Patients with cured skin basal or squamous cell carcinoma and cervical carcinoma in situ at any time before the study were not included; Patients with other tumors not listed above, but which have been cured by surgery but not by other further treatment measures, and disease-free survival≥5 years, can be included in the study; Patients with primary immunodeficiency or autoimmune diseases, but asymptomatic hypothyroidism, or well controlled type I diabetes can participate in this study; Patients who participated in other clinical trials within 4 weeks before blood collection; The investigator considers that there are other factors that are not suitable for inclusion or affect the subjects to participate in or complete the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: BT-007 CD7 CAR-T cells in R/R T-LBL<br>Subjects will receive BT-007 CD7 CAR-T cells infusion on Day 0 : 100% of total dose. | Biological: BT-007 CD7 CAR-T cells<br>* T cells purified from the peripheral blood mononuclear cell (PBMC) of subjects or subjects' relatives which depend on their conditions, transduced with 4-1BB/CD3ζ lentiviral vector, expanded in vitro for future administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | The percentage of participants who achieved complete remission (CR) over all participants. The tumor status of patient is assessed for the baseline when assigned into treatment group. The overall CR is assessed by the Lugano Classification Lymphoma Response Criteria 2014 on Day 28, Month 3, Month 6, as well as Month 24 for termination. The overall CR is also assessed for the case withdraw from treatment before the termination of 24 months. The percentage of participants who achieved partial remission (PR) over all participants. The assessment criteria and time frame are the same as CR. | The changes between baseline and Day 28, Month 3, Month 6, as well as Month 24 for termination. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The retention amount of CAR-T cells remaining in vivo | The retention amount of CAR-T cells in all subjects within 24 months when terminated. The retention amount of CAR-T cells in all subjects is assessed on Day 1, 7, 14, 28 during first month after cell infusion. The retention amount is also assessed every month during Month 2 and 6, and every three months during Month 6 and 24 when terminated. | The retention amount of CAR-T cells in all subjects is assessed on Day 1, 7, 14, 28 during first month after cell infusion, and every month during Month 2 and 6, and every three months during Month 6 and 24 when terminated. | 
| The retention time of CAR-T cells remaining in vivo | The retention time of CAR-T cells in all subjects within 24 months when terminated. The retention time of CAR-T cells in all subjects is assessed on Day 1, 7, 14, 28 during first month after cell infusion. The retention time is also assessed every month during Month 2 and 6, and every three months during Month 6 and 24 when terminated. | The retention time of CAR-T cells in all subjects is assessed on Day 1, 7, 14, 28 during first month after cell infusion, and every month during Month 2 and 6, and every three months during Month 6 and 24 when terminated. |