DALY II USA/MB-CART2019.1 for DLBCL

You may be able to join if

• 1. Histologically confirmed DLBCL or associated subtype, defined by WHO 2016 classification: o DLBCL not otherwise specified (NOS) o High-grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements o High-grade B cell lymphoma, NOS o Primary mediastinal (thymic) large B cell lymphoma o Transformed lymphoma (e.g. transformed follicular or marginal zone lymphoma, follicular lymphoma Grade 3) 1.1. CNS Cohort only: B-cell primary or secondary central nervous system lymphoma (PCNSL or SCNSL) 2. Relapsed or refractory disease after 2 or more lines of chemotherapy including rituximab and anthracycline and either having failed autologous stem cell transplant (ASCT), or ineligible, not intended for or not consenting to ASCT (only 2.4 applicable to CNS cohort) 2.1. Chemotherapy-refractory disease is defined as one or more of the following: • Persistent disease after last line of therapy: o Progressive disease (PD) as best response to most recent therapy regimen o Stable disease (SD) as best response to most recent therapy o Partial response (PR) with measurable lesion(s) and Deauville score of at least 4, that in the opinion of the investigator requires change of treatment to CAR-T for improvement in treatment outcome OR • Relapsed or persistent disease after prior ASCT for lymphoma o If salvage therapy is given post-ASCT, the individual must have had persistent disease (as described above) or relapsed after the last line of therapy 2.2. Disease relapse in subjects without prior ASCT is defined as relapse of disease after the last dose of most recent therapy regimen 2.3. Not intended for ASCT is defined as meeting one of the following criteria: • Chemotherapy-refractory disease after salvage therapy • Disease progression or relapse ≤ 12 months after salvage therapy • Intolerance to salvage therapy • Age ≥ 70 2.4. CNS Cohort: Subjects with relapsed/refractory PCNSL that have failed (or unable to tolerate) first-line therapy: • First-line therapy is defined as either high dose methotrexate-based therapy, temozolomide, high dose cytarabine, pemetrexed, lenalidomide or bruton thyrosine kinase (BTK) inhibitor-based therapy. • Unable to tolerate therapy is defined as Grade 3+ acute kidney injury (AKI) and/or transaminitis preventing repeat treatment exposure • Persistent disease after last line of therapy (as in 2.1) • No contraindications for MRI evaluation 2.5. CNS Cohort: Subjects with SCNSL must have relapsed or refractory disease after having received at least 1 prior line of systemic therapy • Prior lines of systemic therapy should include an anti- CD20 monoclonal antibody and anthracycline containing chemotherapy regimen and/or an autologous stem cell transplant • No contraindications for MRI evaluation In addition, all subjects must have: 3. Age ≥18 years 4. Eastern Cooperative Oncology Group (ECOG) performance status that is either 0 or 1 at screening. ECOG performance status of 2 at screen is allowed if the decrease in performance status is due to DLBCL 5. Measurable disease according to Lugano 2014 criteria for assessing FDG-PET/CT in lymphoma (Cheson et al, 2014) for DLBCL and SCNSL while IPCG criteria for the primary PCNSL.
• Continued translation (1-5)
• 6. CD19 or CD20 antigen expression on tumor is not required after the most recent chemoimmunotherapy; however, 6.1 Subject must have a tumor biopsy sample (at least 16 unstained slides of tissue or tissue block) from the most recent relapse available prior to MB-CART2019.1 infusion. If medically not feasible to obtain a biopsy from the most recent relapse and for cases when the amount of tissue is limited, the sponsor should be consulted, to confirm adequacy of the sample for study required analyses 6.2 If archival tissue is not available, subject must be willing to undergo attempted repeat biopsy. 7. No clinical suspicion of central nervous system (CNS) lymphoma (not applicable to CNS cohort) 8. If the subject has history of CNS disease (not applicable to CNS cohort), then he/she must 8.1. Have no signs or symptoms of CNS disease 8.2. Have no active disease on magnetic resonance imaging (MRI) 8.3. Have no large cell lymphoma present in cerebral spinal fluid (CSF) on cytospin preparation and flow cytometry, regardless of the number of white blood cells (WBCs) 9. If has history of cerebral vascular accident (CVA) 9.1. The CVA event must be greater than 12 months prior to leukapheresis 9.2. Any neurological deficits must be stable 10. A creatinine clearance (as estimated by direct urine collection or Cockcroft-Gault Equation) > 60mL/min 11. Cardiac ejection fraction (EF) ≥ 45% as determined by an echocardiogram (ECHO) or Multigated Radionuclide Angiography (MUGA) 12. Resting O2 saturation >90% on room air 13. Serum alanine aminotransferase (ALT) / aspartate aminotransferase (AST) <5 times the Upper Limit of Normal (ULN) for age 14. Total bilirubin <1.5 mg/dl, except in individuals with Gilbert’s syndrome 15. Absolute neutrophil count (ANC) > 1000/μL 16. Absolute lymphocyte count > 100/μL 17. Platelet count > 50,000/μL 18. Estimated life expectancy of more than 3 months other than primary disease 19. Subjects of childbearing or childfathering potential must be willing to practice birth control from the time of enrollment on this study until the follow-up period of the study