CD79b-19 CAR T Cells for the Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma

Inclusion Criteria

• INCLUSION CRITERIA FOR LEUKAPHERESIS FOR PARTS A AND B: Voluntarily sign informed consent form(s)
• INCLUSION CRITERIA FOR LEUKAPHERESIS FOR PARTS A AND B: ≥ 18 years of age at the time of signing informed consent
• INCLUSION CRITERIA FOR LEUKAPHERESIS FOR PARTS A AND B: Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnofsky ≥ 60%)
• INCLUSION CRITERIA FOR LEUKAPHERESIS FOR PARTS A AND B: Diagnosis of histologically or cytologically confirmed relapsed/refractory (R/R) Non-Hodgkins lymphoma as defined as one of the following (Note: only patients with indolent lymphomas that warrant treatment should be treated, this will include those with local symptoms due to progressive/bulky disease, compromised organ function, B symptoms, extra-nodal disease, cytopenias from marrow involvement and/or in the opinion of the treating physician believe that any of the above symptoms or potentially life threatening involvement will occur will be treated): * Follicular lymphoma (FL) grade 1, grade 2, or grade 3a ** R/R disease after 2 or more prior lines of systemic therapy * Marginal zone lymphoma (MZL) nodal or extranodal: ** R/R disease after 2 or more prior lines of systemic therapy * Diffuse large B-cell lymphoma (DLBCL), including transformed follicular lymphoma (FL), primary mediastinal B-cell lymphoma (PMBCL), high-grade B-cell lymphoma (HGBCL) and grade 3b follicular lymphoma (FL) ** R/R disease after 2 or more prior lines of therapy OR ** Relapsed following autologous stem cell transplantation (SCT), OR ** Ineligible for autologous SCT. * Mantle cell lymphoma ** R/R disease as defined by disease progression after last regimen (including autologous SCT) OR ** Refractory disease as defined as failure to achieve a complete response (CR) to last regimen ** Prior therapy must include: *** Anthracycline or bendamustine-containing chemotherapy AND *** Anti-CD20 monoclonal antibody therapy AND *** BTK inhibitor (BTKi) therapy (progression does not have to be documented on BTKi)
• INCLUSION CRITERIA FOR LEUKAPHERESIS FOR PARTS A AND B: Subjects must have measurable disease according to appropriate disease specific criteria
• INCLUSION CRITERIA FOR LEUKAPHERESIS FOR PARTS A AND B: Adequate absolute lymphocyte count (ALC > 100 cells/ul) within one week of apheresis
• INCLUSION CRITERIA FOR LEUKAPHERESIS FOR PARTS A AND B: Adequate bone marrow function defined by absolute neutrophil count (ANC) > 1000 cells/mm^3 without growth factor support (filgrastim within 7 days or pegfilgrastim within 14 days) and untransfused platelet count > 50,000 mm^3
• INCLUSION CRITERIA FOR LEUKAPHERESIS FOR PARTS A AND B: Left ventricular ejection fraction > 40%
• INCLUSION CRITERIA FOR LEUKAPHERESIS FOR PARTS A AND B: Adequate hepatic function defined by aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 × upper limit of normal (ULN) and direct bilirubin < 1.5 × ULN
• INCLUSION CRITERIA FOR LEUKAPHERESIS FOR PARTS A AND B: Adequate renal function defined by creatinine clearance > 60 ml/min using the Cockcroft-Gault formula
• INCLUSION CRITERIA FOR LEUKAPHERESIS FOR PARTS A AND B: The effects of CD79b-19 CAR T cells on the developing human fetus are unknown. For this reason, women of child-bearing potential and men with partners of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to leukapheresis. Women of childbearing potential are required to use adequate contraception for up to 1 year post CD79b-19 CAR T cell infusion. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men with partners of childbearing potential treated or enrolled on this protocol must also agree to use adequate contraception prior to the study and until 6 months after last CD79b-19 CAR T cells administration
• INCLUSION CRITERIA FOR LEUKAPHERESIS FOR PARTS A AND B: Ability and willingness to adhere to the study visit schedule and all protocol requirements
• INCLUSION CRITERIA FOR TREATMENT (INITIATING LYMPHODEPLETION/CELL INFUSION): Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnofsky ≥ 60%)
• INCLUSION CRITERIA FOR TREATMENT (INITIATING LYMPHODEPLETION/CELL INFUSION): No active, uncontrolled, systemic bacterial, viral, or fungal infection. If febrile, the patient must have negative blood cultures negative x48 hours at the time of cell infusion AND be on appropriate broad spectrum antibiotic therapy
• INCLUSION CRITERIA FOR TREATMENT (INITIATING LYMPHODEPLETION/CELL INFUSION): Oxygen saturation > 92% on room air while awake
• INCLUSION CRITERIA FOR TREATMENT (INITIATING LYMPHODEPLETION/CELL INFUSION): No additional anti-cancer therapy since leukapheresis, with the exception steroids at or below physiologic dosing and bridging therapy

Exclusion Criteria

• EXCLUSION CRITERIA FOR LEUKAPHERESIS FOR PARTS A AND B: Treatment with an any investigational cellular therapy within 8 weeks prior to apheresis
• EXCLUSION CRITERIA FOR LEUKAPHERESIS FOR PARTS A AND B: No bispecific T cell engagers within 6 months of leukapheresis
• EXCLUSION CRITERIA FOR LEUKAPHERESIS FOR PARTS A AND B: No bendamustime within 6 months of leukapheresis
• EXCLUSION CRITERIA FOR LEUKAPHERESIS FOR PARTS A AND B: Any systemic anti-cancer therapy within 1 week or five half-lives of leukapheresis, whichever is shortest, excluding steroids (prednisone) at or below physiologic dosing (5mg)
• EXCLUSION CRITERIA FOR LEUKAPHERESIS FOR PARTS A AND B: Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine or systemic steroids above physiologic dosing). Intermittent topical, inhaled, or intranasal corticosteroids are allowed
• EXCLUSION CRITERIA FOR LEUKAPHERESIS FOR PARTS A AND B: Ongoing systemic immunosuppression for acute and/or chronic graft versus host (GVH) as a result of previous allogeneic bone marrow transplant and at least 12 weeks out from prior allogeneic SCT
• EXCLUSION CRITERIA FOR LEUKAPHERESIS FOR PARTS A AND B: Presence of active central nervous system (CNS) disease
• EXCLUSION CRITERIA FOR LEUKAPHERESIS FOR PARTS A AND B: Significant co-morbid condition or disease which in the judgment of the principal investigator would place the subject at undue risk or interfere with the study; examples include, but are not limited to, cirrhotic liver disease, sepsis, and/or recent significant traumatic injury
• EXCLUSION CRITERIA FOR LEUKAPHERESIS FOR PARTS A AND B: Active, uncontrolled, systemic bacterial, viral, or fungal infection
• EXCLUSION CRITERIA FOR LEUKAPHERESIS FOR PARTS A AND B: Subjects with a history of class III or IV congestive heart failure or with a history of nonischemic cardiomyopathy
• EXCLUSION CRITERIA FOR LEUKAPHERESIS FOR PARTS A AND B: Subjects with unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the previous 3 months
• EXCLUSION CRITERIA FOR LEUKAPHERESIS FOR PARTS A AND B: Subjects with arterial vascular disease such as history of cerebrovascular accident or peripheral vascular disease requiring therapeutic anti-coagulation
• EXCLUSION CRITERIA FOR LEUKAPHERESIS FOR PARTS A AND B: Subjects with history of a new pulmonary embolism (PE) /deep vein thrombosis (DVT) within 6 months of beginning lymphodepletion requiring ongoing anticoagulation
• EXCLUSION CRITERIA FOR LEUKAPHERESIS FOR PARTS A AND B: Subjects with second malignancies if the second malignancy has required therapy in the last 3 years or is not in complete remission; exceptions to this criterion include successfully treated non-metastatic basal cell or squamous cell skin carcinoma, or prostate cancer that does not require therapy other than hormonal therapy
• EXCLUSION CRITERIA FOR LEUKAPHERESIS FOR PARTS A AND B: Pregnant or lactating women. Pregnant women are excluded from this study because CAR-79b-19 T cell drug product is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CAR-79b-19 T cell drug product, breastfeeding should be discontinued if the mother is treated with CAR-79b-19 T cell drug product
• ADDITIONAL EXCLUSION CRITERIA FOR LEUKAPHERESIS FOR PART B, ARM B.2: Prior CD19-directed cellular therapy