CAR T Cells for Refractory B Cell Malignancy

Study Overview
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Brief Summary
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Chimeric antigen receptor (CAR) T cells targeting CD19 will be evaluated for safety and efficacy in patients with B cell malignancy including lymphoma or leukemia.

Detailed Description
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The CAR consists of a CD19 targeting antibody scFv with three intracellular signaling domains derived from CD3 zeta, CD28 and 4-1BB. Autologous T cells will be gene engineered with the CAR gene using a lentivirus vector. Prior to T cell infusion, the patients will be subjected to preconditioning treatment. After T cell infusion, the patients will be evaluated for 24 months for adverse reactions, persistence of CAR T cells and efficacy.

Official Title
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Autologous CD19-targeting CAR T Cells for Refractory B Cell Malignancy

Conditions
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B-Cell Leukemia, B-Cell Lymphoma

Intervention / Treatment
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* Biological: Autologous CD19-targeting CAR T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The treat history meeting the following criteria: Recurrence of lymphoma patients with imaging (CT/MRI/PET-CT) detection and pathological diagnosis, or recurrence including bone marrow morphology relapse and the MRD recurrence of myeloma patients or leukemia patients, after chemotherapy or stem cell transplantation; Can't get complete remission (including MRD positive) after more than twice repeated chemotherapy of incipient lymphoma, myeloma or leukemia patients; One or twice chemotherapy cannot get remission again (including MRD positive), but not suitable for chemotherapy of incipient lymphoma, myeloma or leukemia patients. There is a measurable lesions before treatment at least; ECOG score≤2; To be aged 1 to 70 years; More than a month lifetime from the consent signing date Exclusion Criteria: Serious cardiac insufficiency, left ventricular ejection fraction<50; Has a history of severe pulmonary function damaging; Merging other malignant tumor; Merging uncontrolled infection; Merging the metabolic diseases (except diabetes); Merging severe autoimmune diseases or immunodeficiency disease; patients with active hepatitis B or hepatitis C; patients with HIV infection; Has a history of serious allergies on Biological products (including antibiotics); Happened in 3   4 acute GvHD after allogeneic hematopoietic stem cell transplantation on recurring patients Pregnancy or lactation women; Any situation that would increase dangerousness of subjects or disturb the outcome of the clinical study according to the researcher's evaluation.

Ages Eligible for Study
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Minimum Age: 1 Year
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: CD19 CAR T cells<br>Autologous CD19-targeting CAR T cells | Biological: Autologous CD19-targeting CAR T cells<br>* Autologous CD19-targeting CAR T cells with three signaling domains derived from CD3zeta, CD28 and 4-1BB.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor load | Tumor load will be quantified with radiology, bone marrow and/or blood samples dependent on diagnosis. | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CAR T cell persistence | Tumor load will be quantified with radiology, bone marrow and/or blood samples dependent on diagnosis | Up to 24 months |