DALY II Japan/MB-CART2019.1 for DLBCL

Inclusion Criteria

• •1. Histologically confirmed DLBCL or associated subtype, defined by WHO 2016 classification:
• •* DLBCL not otherwise specified (NOS)
• •* High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements
• •* High-grade B-cell lymphoma, NOS
• •* Primary mediastinal (thymic) large B-cell lymphoma
• •* Transformed lymphoma (e.g. transformed follicular or marginal zone lymphoma, follicular lymphoma Grade 3B)
• •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 being ineligible for or not consenting to ASCT 2.1 Chemotherapy-refractory disease is defined as one of the following:
• •* No response to last line of therapy:
• •* Progressive disease (PD) as best response to most recent therapy regimen
• •* Stable disease (SD) as best response to most recent therapy with duration no longer than 6 months from last dose of therapy OR
• •* Relapsed or persistent disease after prior ASCT for lymphoma
• •* Disease progression or relapse less than or equal to 24 months of ASCT
• •* If salvage therapy is given post-ASCT, the individual must have had no response to or relapsed after the last line of therapy 2.2 Disease relapse in subjects without prior ASCT is defined as relapse of disease in ≤ 12 months after the last dose of most recent therapy regimen 2.3 Ineligible 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
• •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 fluorodeoxyglucose-positron emission tomography (FDG-PET)/computer tomography (CT) in lymphoma (Cheson et al, 2014)
• •6. CD19 or CD20 antigen expression on tumor is not required after the most recent chemoimmunotherapy; however, 6.1 Subject must have at least 20 unstained slides of tissue available prior to MB-CART2019.1 infusion 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
• •8. If the subject has history of CNS disease, 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 the subject 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. An estimated creatinine clearance by Cockcroft-Gault Equation (eGFR) \> 60mL/min
• •11. Cardiac ejection fraction (EF) ≥ 45% as determined by an echocardiogram (ECHO)
• •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 child fathering potential must be willing to practice birth control from the time of enrollment on this study until the follow-up period of the study