Phase I Clinical Trial of Autologous CD7-CAR T Cells in the Treatment of High-risk Acute T-cell Leukemia / Lymphoma

Study Overview
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Brief Summary
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This is a phase 1 clinical trial of autologous CD7-CAR T cells in the treatment of high-risk acute T-cell leukemia / lymphoma. Twenty subjects will be enrolled. Subjects will be pretreated with chemotherapy prior to infusion of CAR T cells: about 3 days before cells transfusion, the patients who planned to reinfuse CAR T cells were treated with fluorodarabine 30 mg/m2( body surface area) and cyclophosphamide 250 mg/m2( body surface area) for 3 days. Then this study will be using a 3+3 dose escalation approach from dose 1 (DL-1): 5×105 (±20%) to dose 2 (dl-2): 1×106 (±20%). Below the lowest dose was reinfused at the PI's discretion.

Official Title
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Phase I Clinical Trial of Autologous CD7-CAR T Cells in the Treatment of High-risk Acute T-cell Leukemia / Lymphoma

Conditions
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T-cell Leukemia, T Cell Lymphoma

Intervention / Treatment
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* Biological: chimeric antigen receptor T cell treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In order to be eligible to participate in this study, an individual must meet all of the following criteria: Diagnosed as a high-risk acute T-cell leukemia / lymphoma patient with complete remission within 3 months and persistent positive of minimal residual disease, expressing tumor surface antigen CD7 Refractory or relapsed T-cell acute lymphoblastic leukemia/lymphoma patients with no blasts in peripheral blood by flow cytometry and suspending anti-neoplastic treatment for more than 2 weeks Male or female, aged 0-70 years No serious allergic constitution Eastern Cooperative Oncology Group (ECOG) performance status (Oken et al., 1982) score 0 to 2 Have life expectancy of at least 60 days based on investigator's judgement CD7 positive in bone marrow or peripheral blood or immunohistochemistry Candidates aged 8-70 years need to be sufficiently conscious and able to sign the treatment consent form and voluntary consent form. And Pediatric patients under 8 years old could be recruited after signing an informed consent form by a legal surrogate (Guardian) Minimal residual disease was positive after chemotherapy and there were contraindications of allogeneic hematopoietic stem cell transplantation. Exclusion Criteria: An individual who meets any of the following criteria will be excluded from participation in this study: Intracranial hypertension or disorder of consciousness Symptomatic heart failure or severe arrhythmia Symptoms of severe respiratory failure Complicated with other types of malignant tumors Diffuse intravascular coagulation Serum creatinine and / or blood urea nitrogen ≥ 1.5 times of the normal value Suffering from septicemia or other uncontrollable infections Patients with uncontrollable diabetes Severe mental disorders Obvious and active intracranial lesions were detected by cranial magnetic resonance imaging (MRI) Have received organ transplantation (excluding hematopoietic stem cell transplantation); Reproductive-aged female patients with positive blood HCG test Screened to be positive of infection of hepatitis (including hepatitis B and C), AIDS or syphilis

Ages Eligible for Study
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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: chimeric antigen receptor T cell treatment<br> | Biological: chimeric antigen receptor T cell treatment<br>* Subjects will be pretreated with chemotherapy prior to infusion of CAR T cells: about 3 days before cells transfusion, the patients who planned to reinfuse CAR T cells were treated with fluorodarabine 30 mg/m2( body surface area) and cyclophosphamide 250 mg/m2( body surface area) for 3 days. Then this study will be using a 3+3 dose escalation approach from dose 1 (DL-1): 5×105 (±20%) to dose 2 (dl-2): 1×106 (±20%). Below the lowest dose was reinfused at the PI's discretion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DLT rate | The DLT rate to the CAR-T treatment | 21 days |