Consolidation of First-Line MRD+ Remission With Cema-cel in Patients With LBCL
- Conditions
- Large B-cell Lymphoma
- Interventions
- Device: Foresight CLARITY™ IUO MRD test, powered by PhasED-Seq™Genetic: cemacabtagene ansegedleucel
- Registration Number
- NCT06500273
- Lead Sponsor
- Allogene Therapeutics
- Brief Summary
This is a randomized, open-label study in adult patients who have completed standard first line 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 250
- LBCL per WHO 2017 including diffuse large B-cell lymphoma, high-grade B-cell lymphoma, and primary mediastinal B-cell lymphoma histologically confirmed by pathology report.
- Participant has completed a full course of standard first line therapy (e.g., R-CHOP, dose-adjusted EPOCH-R, Pola-R-CHP) as intended. Participants cannot have received additional lines of therapy.
- Participant achieved CR, or PR suitable for observation at the end of first line therapy based on PET/CT evaluation
- Foresight CLARITY™ IUO MRD test, powered by PhasED-Seq™, is positive.
- Adult participants ≥18 years of age.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
- Adequate hematological, renal, hepatic, pulmonary, and cardiac function
- Non-hematologic toxicities related to prior therapy must be recovered to baseline or grade ≤1.
Key
- LBCL with history of central nervous system involvement, transformed from other malignancy (e.g., transformed follicular lymphoma or marginal zone lymphoma, Richter's transformation), or T-cell/histiocyte rich LBCL.
- Prior treatment with anti-CD19 targeted therapies.
- Anti-cancer treatment, including radiation, after end of treatment PET/CT and/or MRD testing is performed.
- Active and clinically significant autoimmune disease.
- Active systemic bacterial, fungal, or viral infections requiring systemic treatment (e.g., HIV).
- History of another primary malignancy or bone marrow disorder (e.g., myelofibrosis, smoldering multiple myeloma) within 3 years prior to enrollment.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Observation Foresight CLARITY™ IUO MRD test, powered by PhasED-Seq™ Participants do not receive any study treatments. They are observed as per the current standard of care. cemacabtagene ansegedleucel, ALLO-647 Foresight CLARITY™ IUO MRD test, powered by PhasED-Seq™ Participants receive cemacabtagene ansegedleucel following lymphodepletion regimen comprised of fludarabine, cyclophosphamide, and ALLO-647. cemacabtagene ansegedleucel cemacabtagene ansegedleucel Participants receive cemacabtagene ansegedleucel following lymphodepletion regimen comprised of fludarabine and cyclophosphamide. cemacabtagene ansegedleucel, ALLO-647 cemacabtagene ansegedleucel Participants receive cemacabtagene ansegedleucel following lymphodepletion regimen comprised of fludarabine, cyclophosphamide, and ALLO-647. cemacabtagene ansegedleucel Foresight CLARITY™ IUO MRD test, powered by PhasED-Seq™ Participants receive cemacabtagene ansegedleucel following lymphodepletion regimen comprised of fludarabine and cyclophosphamide. cemacabtagene ansegedleucel, ALLO-647 ALLO-647 Participants receive cemacabtagene ansegedleucel following lymphodepletion regimen comprised of fludarabine, cyclophosphamide, and ALLO-647. cemacabtagene ansegedleucel Fludarabine Participants receive cemacabtagene ansegedleucel following lymphodepletion regimen comprised of fludarabine and cyclophosphamide. cemacabtagene ansegedleucel, ALLO-647 Fludarabine Participants receive cemacabtagene ansegedleucel following lymphodepletion regimen comprised of fludarabine, cyclophosphamide, and ALLO-647. cemacabtagene ansegedleucel, ALLO-647 Cyclophosphamide Participants receive cemacabtagene ansegedleucel following lymphodepletion regimen comprised of fludarabine, cyclophosphamide, and ALLO-647. cemacabtagene ansegedleucel Cyclophosphamide Participants receive cemacabtagene ansegedleucel following lymphodepletion regimen comprised of fludarabine and cyclophosphamide.
- Primary Outcome Measures
Name Time Method Event-free survival per independent review committee assessment Up to 60 months
- Secondary Outcome Measures
Name Time Method 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 Up to 60 months 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.
Incidence and severity of laboratory toxicities related to cemacabtagene ansegedleucel and ALLO-647 Up to 60 months Change from baseline value and NCI toxicity grading of laboratory values outside of normal ranges using CTCAE version 5.0.
Minimal residual disease clearance Up to 60 months
Trial Locations
- Locations (46)
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
Alta Bates Summit Medical Center
🇺🇸Berkeley, California, United States
City of Hope
🇺🇸Duarte, California, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
University of California, Los Angeles
🇺🇸Los Angeles, California, United States
University of California, Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
University of California, San Diego
🇺🇸San Diego, California, United States
University of California, San Francisco
🇺🇸San Francisco, California, United States
Rocky Mountain Cancer Centers
🇺🇸Denver, Colorado, United States
Medical Oncology Hematology Consultants
🇺🇸Newark, Delaware, United States
MedStar Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
Miami Cancer Institute at Baptist Health, Inc.
🇺🇸Miami, Florida, United States
Advent Health Cancer Institute
🇺🇸Orlando, Florida, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Augusta University Georgia Cancer Center
🇺🇸Augusta, Georgia, United States
Indiana Blood and Marrow Transplantation
🇺🇸Indianapolis, Indiana, United States
The University of Kansas Hospital
🇺🇸Kansas City, Kansas, United States
University of Kentucky Medical Center
🇺🇸Lexington, Kentucky, United States
University of Louisville Health Brown Cancer Center
🇺🇸Louisville, Kentucky, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Washington University School of Medicine - Siteman Cancer Center
🇺🇸Saint Louis, Missouri, United States
Astera Cancer Care
🇺🇸East Brunswick, New Jersey, United States
John Theurer Cancer Center
🇺🇸Hackensack, New Jersey, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Columbia University Irving Medical Center and New York-Presbyterian Hospital
🇺🇸New York, New York, United States
Duke Blood Cancer Center
🇺🇸Durham, North Carolina, United States
Oncology Hematology Care - Kenwood
🇺🇸Cincinnati, Ohio, United States
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Oncology Associates of Oregon
🇺🇸Eugene, Oregon, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Texas Oncology - Central South
🇺🇸Austin, Texas, United States
Texas Oncology - Dallas Fort Worth
🇺🇸Dallas, Texas, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Texas Transplant Institute
🇺🇸San Antonio, Texas, United States
Texas Oncology - Tyler
🇺🇸Tyler, Texas, United States
Huntsman Cancer Institute, University of Utah
🇺🇸Salt Lake City, Utah, United States
Intermountain Health LDS Hospital
🇺🇸Salt Lake City, Utah, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Virginia Oncology Associates - Norfolk
🇺🇸Norfolk, Virginia, United States
Fred Hutchinson Cancer Center
🇺🇸Seattle, Washington, United States