Study of CAR-20/19-T Cells in Patients With Relapsed Refractory B Cell

Inclusion Criteria

• Diagnosis of B-cell non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL) / small lymphocytic leukemia (SLL): Patients must be aged≥18 years with relapsed, refractory disease and no available curative options that meet clinical criteria to initiate treatment.
• Patients with B-cell NHL or CLL/SLL must have either CD19 or CD20 positive disease on most recent biopsy performed (a repeat biopsy is not mandatory for this study except as noted below). A minimum of 5% CD19 or CD20 positivity by immunohistochemistry or flow cytometry on prior or repeat biopsy is required.
• Absolute CD3+ T cell count ≥50/mm^3.
• MRI brain and Lumbar Puncture with cerebral spinal fluid (CSF) analysis by cytology and flow cytometry without evidence of central nervous system (CNS) involvement only in patients with history of CNS involvement.
• Measurable disease must have been documented within 4 weeks of the time of consent defined as the following by disease specific subtype:
• B-cell NHL: Active disease defined as nodal lesions greater than 20 mm in the long axis or extranodal lesions >10 mm in long and short axis or bone marrow involvement that is biopsy proven.
• CLL/SLL: Active disease by either bone marrow, peripheral flow cytometry, or CT and/or positron emission tomography (PET) imaging with nodal disease.
• Patients should have failed at least two lines of a standard treatment and meet disease specific criteria detailed below:
• CLL/SLL: measurable disease as defined above that has relapsed after at least one line of chemo-immunotherapy and progressed or intolerant to ibrutinib monotherapy.
• CD19 or CD20 positive B cell NHL limited to the following histologies: Advanced Stage III or IV Follicular Lymphoma, Diffuse Large B cell Lymphoma and associated subtypes (e.g. aggressive B-cell lymphoma, T-cell/histocyte rich B-cell lymphoma, primary mediastinal B-cell lymphoma, Epstein Barr virus positive diffuse large B-cell lymphoma, transformed lymphoma such as transformed follicular or marginal zone lymphoma, and Richter's transformation) and Mantle cell lymphoma. Specific criteria include:
• Patients must have active, measurable disease after two lines of cytotoxic chemotherapy of which one must be anthracycline containing.
• Must have received Rituximab or another CD20 antibody and at minimum two chemotherapy regimens appropriate for their disease.
• Either failed autologous transplant or ineligible to receive autologous transplant
• Karnofsky performance score ≥70. See Appendix A for scales.
• Normal Baseline Neurological Evaluation: Mini-Mental Status Exam Score 24-30.
• Adequate hepatic function, defined as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 60 ml/min
• Able to provide written informed consent.
• Agree to practice birth control during the study.
• Adequate cardiac function as indicated by New York Heart Association (NYHA) classification I or II AND left ventricular ejection fraction of ≥35% (by echocardiogram or MUGA) and adequate pulmonary function as indicated by room air oxygen saturation of ≥92%.
• Expected survival >12 weeks.
• Negative urine or serum pregnancy test in females of child bearing potential at study entry and again within 48 hours' prior lymphodepleting chemotherapy.
• Patients with prior blinatumomab treatment require repeat biopsy post-blinatumomab treatment that demonstrates CD19 or CD20 positive disease.
• Meet criteria for regarding fertility and contraception.
• Central line access will be required for CAR-20/19-T cell infusion.

Exclusion Criteria

• Positive beta-human chorionic gonadotropin in females of child-bearing potential.
• Patients with known systemic allergy to bovine or murine products.
• Known prior positive serology for human anti-mouse antibody (HAMA).
• Confirmed active human immunodeficiency virus (HIV), Hepatitis B or C infection.
• History of significant autoimmune disease OR active, uncontrolled auto