Consolidation of First-Line MRD+ Remission With Cema-cel in Patients With LBCL
NCT Number: NCT06500273
Acronym: ALPHA3
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Large B-cell Lymphoma
Interventions: GENETIC: cemacabtagene ansegedleucel|BIOLOGICAL: ALLO-647|DRUG: Fludarabine|DRUG: Cyclophosphamide|DEVICE: Foresight CLARITY™ IUO MRD test, powered by PhasED-Seq™
Sponsor: Allogene Therapeutics
Collaborators: Foresight Diagnostics, Inc.
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 250
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-06-18
Completion Date: 2031-08-24
Locations: Alta Bates Summit Medical Center, Berkeley, California, 94704, United States|Rocky Mountain Cancer Centers, Denver, Colorado, 80218, United States|Norton Cancer Institute, Louisville, Kentucky, 40207, United States|Astera Cancer Care, East Brunswick, New Jersey, 08816, United States|Oncology Hematology Care - Kenwood, Cincinnati, Ohio, 45236, United States|Oncology Associates of Oregon, Eugene, Oregon, 97401, United States|Texas Oncology - Dallas Fort Worth, Dallas, Texas, 75246, United States|Texas Oncology - Tyler, Tyler, Texas, 75702, United States|University of Virginia, Charlottesville, Virginia, 22903, United States|Virginia Cancer Specialists, Fairfax, Virginia, 22031, United States|Virginia Oncology Associates - Norfolk, Norfolk, Virginia, 23502, United States

Summary:
This is a randomized, open-label study in adult patients who have completed standard first line of therapy for large B-cell lymphoma (LBCL) and achieved a complete response or partial response suitable for observation, but who have minimal residual disease (MRD) as detected by the Foresight CLARITY™ Investigational Use Only (IUO) MRD test, powered by PhasED-Seq™. The purpose of the trial is to assess the efficacy and safety of consolidation with cemacabtagene ansegedleucel (cema-cel), an allogeneic CD19 CAR T product, as compared to standard of care observation.

The study is conducted in 2 consecutive parts that will be enrolled continuously. In Part A of the study, participants with MRD are randomized to one of two treatment arms or an observation arm. Treatment includes cema-cel following a lymphodepletion regimen of fludarabine and cyclophosphamide administered with or without the anti-CD52 monoclonal antibody, ALLO-647. Part A will culminate with the selection of the lymphodepletion regimen to advance to Part B. Part B will evaluate the selected lymphodepletion regimen followed by cema-cel as compared with observation.

Primary Outcome Measures: Event-free survival per independent review committee assessment, Up to 60 months
Secondary Outcome Measures: Progression-free survival per independent review committee assessment, Up to 60 months|Overall survival, Up to 60 months|Incidence and severity of adverse events and their relationship to cemacabtagene ansegedleucel and ALLO-647, Adverse events, treatment emergent adverse events, serious adverse events, and adverse events of special interest evaluated by the investigator based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. CRS and ICANS will be graded using ASTCT., Up to 60 months|Incidence and severity of laboratory toxicities related to cemacabtagene ansegedleucel and ALLO-647, Change from baseline value and NCI toxicity grading of laboratory values outside of normal ranges using CTCAE version 5.0., Up to 60 months|Minimal residual disease clearance, Up to 60 months