Optimizing lymphoDepletion to Improve Outcomes In Patients Receiving CAR T Cell Therapy With Yescarta/AxicabtageNeciloleucel (ODIN)
This is a Phase 1b study of participants with Diffuse Large B Cell Lymphoma (DLBCL). The purpose of this study is to identify an optimized lymphodenpletion (LD) regimen by evaluating standard and intermediate doses of Fludarabine (Flu) / Cyclophosphamide (Cy) with or without a fixed dose of total lymphoid irradiation (TLI) in the setting of standard of care CAR T cell therapy.
• Age ≥ 18 years at the time of informed consent
• Life expectancy ≥ 12 weeks
• Biopsy-proven and histologically confirmed R/R large B cell lymphoma, including R/R DLBCL, transformation from FL, and R/R PMBCL.
• Radiographically documented measurable disease as per Lugano response criteria (i.e. LDi \> 1.5 cm that is FDG avid).
• At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic cancer therapy at the time the subject provides consent
• Eligible for standard of care CAR T cell therapy, specifically, relapsed or refractory large B cell lymphoma after two or more lines of systemic therapy, and subjects must have received adequate first-line therapy including at a minimum:
‣ Anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20 negative, and
⁃ An anthracycline containing chemotherapy regimen
• Patient does not have active CNS disease
• Patient is sufficiently stable to facilitate planned CAR T-cell therapy (e.g. not rapidly progressing on temporizing therapy, no significant compromise of vital organ functions (intubation, dialysis, requiring ICU/vasopressor support)) and has good performance status
• ECOG performance status 0 or 1 at enrollment
⁃ Patient has not received prior adoptive T-cell immunotherapy
⁃ Patient is not HIV positive
⁃ Patient did not receive prior allogeneic stem cell transplant
⁃ Adequate bone marrow, renal, hepatic, pulmonary and cardiac function
⁃ Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential)
⁃ Sexually active males who accept to use a condom during intercourse during treatment and for 6 months after treatment as they should not father a child in this period. A condom is required to be used also by vasectomized men (as well as during intercourse with a male partner) in order to prevent delivery of the drug via seminal fluid
⁃ Must have an apheresis product of non-mobilized cells accepted for manufacturing.