NCT05950802

Optimizing lymphoDepletion to Improve Outcomes In Patients Receiving Cell Therapy With Yescarta

Optimizing lymphoDepletion to Improve Outcomes In Patients Receiving CAR T Cell Therapy With Yescarta/AxicabtageNeciloleucel (ODIN)

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: University Health Network, Toronto · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

Patients will be enrolled in two stages: the dose escalation stage to assess the safety and tolerability of a modified LD regimen, and once the maximum tolerated dose (MTD) is determined, a cohort expansion phase to further characterize the toxicity and efficacy profile and determine the recommended phase 2 dose (RP2D). The study will enroll approximately 18-24 patients in the dose escalation stage (Part 1), and approximately 20 further patients at cohort expansion (Part 2). There will be four dose escalation cohorts, in two study arms. There are two dosing cohorts in each study arm. Patients in Arm 1 will receive the ZUMA-1 chemotherapy LD regimen with or without TLI, and in Arm 2, an intermediate dose of Cy with a fixed dose of Flu, with or without TLI, will be given. The cohorts in Arm 1 will enroll concurrently, and enrollment into Arm 2 will begin after Arm 1 has enrolled all patients and data review by the Trial Steering Committee (TSC). For accrual into Cohort 2, Arm 1, there will be a 15-day staggered enrollment for the first 2 patients. Staggered enrollment with another 15-day delay may be considered for enrollment into Cohorts 3 and 4, Arm 2, after review by the TSC. Following completion of accrual to Arm 1, a 30 day dose-limiting toxicity (DLT) window will be observed, prior to review by the TSC and commencement of enrollment into Arm 2.

Conditions

• DLBCL - Diffuse Large B Cell Lymphoma

Interventions

Type	Name	Description
DRUG	Cyclophosphamide	Higher dose than traditional conditioning chemo
RADIATION	TLI	radiation given with conditioning chemo

Timeline

• Start date: 2023-07-14
• Primary completion: 2027-09-01
• Completion: 2027-09-01
• First posted: 2023-07-18
• Last updated: 2025-12-08

Locations

1 site across 1 country: Canada