AutologousCD22 Chimeric Antigen Receptor (CAR)T Cells in w/Recurrent/Refractory B Cell Lymphomas

Inclusion Criteria

• •Disease: Must have histologically confirmed disease as defined by WHO 2016\[117\] of one of the following:
• •Follicular Lymphoma, grade 1-3a
• •1. Relapsed or refractory disease after at least 2 lines of systemic therapy. Prior therapy must have included an anti-CD20 monoclonal antibody combined with systemic therapy (single-agent anti- CD20 antibody does not count as line of therapy for eligibility nor does local radiation). Anti-CD20 antibody is not required for participants with CD20 negative disease. A systemic therapy includes, but is not limited to: Bendamustine, CHOP, CVP, CART therapy, lenalidomide, or platinum-based chemotherapy.
• •Mantle Cell Lymphoma 1. Relapsed or refractory disease after at least 2 lines of systemic therapy. Prior therapy must have included an anti-CD20 monoclonal antibody combined with systemic therapy. Anti-CD20 antibody is not required for participants with CD20negative disease.
• •2\. Participants who have received an anti-CD20 monoclonal antibody in combination with chemotherapy AND a Bruton's Tyrosine Kinase inhibitor as a single line of therapy are also eligible.
• •Hairy cell leukemia (HCL)
• •1. Diagnosis of HCL and require treatment as defined by having HCL-related anemia (hemoglobin \<11 g/dL), thrombocytopenia (platelets\<100 x 10\^9 /L), or neutropenia (absolute neutrophil count below 1.5 x 10\^9/L); symptomatic splenomegaly or adenopathy; or other constitutional symptoms directly related to HCL;
• •2. Must have progressed or been refractory to 2 lines of therapy including a purine nucleoside analog.
• •Lymphoplasmacytic lymphoma (Waldenstrom macroglobulinemia (WM)) - participants must meet all eligibility criteria listed
• •1\. Must have confirmed diagnosis of WM based on Second International Workshop on WM 2. Relapsed or refractory disease after 2 or more lines of therapy
• •1\. Prior therapies must include a i. BTKi ii. either chemotherapy and/or proteasome inhibitor 3. Requires treatment based on the recommendations from the Second International Workshop on WM 4. Requires the presence of serum IgM that is at least 2 times the upper limit of normal 5. Patients cannot require plasmapheresis for symptomatic hyperviscosity. 6. Patients cannot have symptomatic central nervous system involvement (Bing-Neel syndrome) that would prevent the assessment of neurotoxicity 7. Patients cannot have transformed to large B cell lymphoma Burkitt lymphoma (BL)
• •1\. Relapsed or refractory to front line chemoimmunotherapy; Participants with high-grade B-cell lymphoma with MYC and BCL2 and/orBCL6 rearrangements will be excluded.
• •Marginal zone lymphoma (MZL)
• •1\. Must have received 2 prior lines of therapy including rituximab in combination with chemotherapy or a BTKi
• •Histologically confirmed Large B-cell lymphoma (LBCL) by WHO 2008 including:
• •i. DLBCL not otherwise specified; DLBCL associated with chronic inflammation; Epstein Barr virus (EBV)+ DLBCL of the elderly; OR ii. primary mediastinal (thymic) large B cell lymphoma; OR iii. transformation of follicular lymphoma, marginal zone lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma to DLBCL; OR iv. Follicular Lymphoma Grade 3B
• •Subjects with DLBCL, Follicular Lymphoma Grade 3B -or-
• •Subjects with transformed FL and MZL who HAVE NOT received chemotherapy prior to transformation:
• •1\) Must have received an anthracycline regimen and an anti CD20 monoclonal antibody (unless documented CD20-negative) and be refractory or relapsed after second line of LBCL treatment. Subjects with a partial response to second line therapy must be ineligible for autologous transplant.
• •Subjects with transformed FL and MZL who HAVE received anthracycline-containing chemotherapy prior to transformation must have progressed, had SD or recurred with transformed disease after initial treatment for LBCL:
• •1. Must have progressed, had SD, or recurred with transformed disease after initial treatment for LBCL
• •6\. Participants with prior CAR therapy must be at least 30 days post CAR infusion and have \< 5% CD3+ cells express the previous CAR prior to apheresis, if a validated assay is available.
• •7\. Toxicities from prior therapy stable or resolved (except for clinically non-significant toxicity and cytopenias covered in footnote).
• •8\. Age ≥ 18 years of age. 9. Adequate performance status (ECOG 0, 1, or 2; or Karnofsky \> 60%) 10. Adequate organ and marrow function as defined by:
• •\- ANC ≥ 750/uL
• •* Platelet count ≥ 50,000/uL
• •* ALC ≥ 150/uL
• •* Adequate renal, hepatic, pulmonary and cardiac function defined as: Creatinine \< 2 mg/dL OR Creatinine clearance (as estimated by Cockcroft Gault Equation) ≥ 45 mL/min, Serum ALT or AST ≤ 10 x ULN (except in participants with liver involvement by lymphoma), Total bilirubin ≤ 1.5 mg/dl, except in participants with Gilbert's syndrome, Cardiac left ventricular ejection fraction ≥ 45%, no evidence of clinically significant pericardial effusion as determined by an Echocardiogram.
• •* No clinically significant pleural effusion or ascites
• •* Baseline oxygen saturation \> 92% on room air ANC Platelet ALC Cr CreatCl AST/ALT Bilirubin LVEF O2 Sat
• •* 11\. Participants with CNS involvement or a history of CNS involvement are eligible only in the absence of neurologic symptoms that may mask or interfere with neurological assessment of toxicity 12. Females of childbearing potential must have negative pregnancy test. 13. Females of child-bearing potential and males of child-fathering potential must be willing to practice birth control from time of enrollment and for 4 months post preparative lymphodepletion regimen or as long as CAR cells are detectable.
• •14\. Must be able to provide informed consent (LAR is permitted if participant able to provide verbal assent).
• •A participant will not be excluded because of pancytopenia ≥ Grade 3 if it is felt by the investigator to be due to underlying disease.