CD19-targeting 3rd Generation CAR T Cells for Refractory B Cell Malignancy - a Phase I/IIa Trial.

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 lymphoma or leukemia. 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 retrovirus 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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CD19-targeting 3rd Generation CAR T Cells for Refractory B Cell Malignancy - a Phase I/IIa Trial.

Conditions
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B Cell Lymphoma, B Cell Leukemia

Intervention / Treatment
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* Biological: Autologous 3rd generation CD19-targeting CAR T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Relapsed or refractory CD19+ B-cell lymphoma or leukemia. Measurable disease. Performance status ECOG 0-2. >18 years old. Fertile females/males must consent to use contraceptives during participation of the trial. Signed informed consent. Exclusion Criteria: Any significant medical or psychiatric illness that would prevent the patient from giving informed consent or from following the study procedures. Patients with primary CNS lymphoma. Known human immunodeficiency virus (HIV) infection. Active and/or severe infection (e.g. tuberculosis, sepsis and opportunistic infections, active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection). Other serious underlying medical conditions, which, in the Investigator's judgment, could impair the ability of the patient. Treatment with an investigational product within 30 days prior to enrollment, or at least 5 half lives of that drug, which is longest. Patients that do not consent to that tissue and blood samples are stored in a biobank. Pregnancy

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CAR T cells<br>Autologous 3rd generation CD19-targeting CAR T cells | Biological: Autologous 3rd generation 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 |
| --- | --- | --- |
| CAR T cell persistence | Presence of circulating CAR T cells will be evaluated with flow cytometry and real time PCR in patient blood. | At week 1 and 5, there after every 3 months post treatment up to 24 months | 

Secondary 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. | Every 3 months post treatment up to 24 months |