CD4-specific CAR T Cells (CD4 CAR T Cells) for Relapsed/Refractory T Cell Malignancies

Study Overview
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Brief Summary
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This is a phase I, interventional, single arm, open label, treatment study to evaluate the safety and tolerability of CD4 CAR T cells in patients with relapsed and/or refractory T cell lymphoma.

Detailed Description
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CD4-specific CAR is a chimeric antigen receptor immunotherapy treatment designed to treat lymphoma/leukemia expressing CD4 antigen. CD4+ T cell lymphomas are a subset of leukemias and lymphomas that are positive for the surface protein CD4. The purpose of this study is to evaluate the efficacy and safety of CD4 CAR T cells.

Official Title
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CD4-specific CAR T Cells (CD4 CAR T Cells) for Relapsed/Refractory T Cell Malignancies

Conditions
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T Cell Lymphoma in Relapse, Refractory T-Cell Lymphoma

Intervention / Treatment
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* Biological: CD4 CAR T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent; Patients volunteer to participate in the research Diagnosis is mainly based on the World Health Organization (WHO) 2008 Patients have exhausted standard therapeutic options Systematic usage of immunosuppressive drug or corticosteroid must have been stopped for more than 1 weeks Female must be not pregnant during the study Exclusion Criteria: Patients declining to consent for treatment Prior solid organ transplantation Potentially curative therapy including chemotherapy or hematopoietic cell transplant Any drug used for GVHD must be stopped >1 week

Ages Eligible for Study
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Minimum Age: 18 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: Sequential Assignment
Interventional Model Description: Dose escalation phase: CD4 CAR T cells transduced with a lentiviral vector to express CD4 chimeric receptor domain on T cells with an escalation approach, 2e6 to 5e6 CAR-T cells/kg
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CD4 CAR T cells<br>Dose escalation phase: CD4 CAR T cells transduced with a lentiviral vector to express CD4 chimeric receptor domain on T cells with an escalation approach, 2e6 to 5e6 CAR-T cells/kg | Biological: CD4 CAR T cells<br>* CD4 CAR T cells administered to patients, will be either fresh or thawed CAR T cells by IV injection after receiving lymphodepleting chemotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events after CD4 CAR T cells cell infusion | Determine the toxicity profile of CD4 CAR T cell therapy | 2 years particularly the first 28 days after infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events | Incidence of treatment-emergent adverse events | up to 6 months | 
| Disease Free Survival (DFS) | Disease Free Survival (DFS) (IMWG criteria) | up to 2 years | 
| Progression-Free Survival (PFS) | Progression-Free Survival (IMWG criteria) | up to 2 years | 
| Overall Survival (OS) | overall survival | up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD4-specific CAR T, T cell leukemia, T cell lymphoma, CD4CAR