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Consolidation of First-Line MRD+ Remission With Cema-cel in Patients With LBCL

Phase 2
Recruiting
Conditions
Large B-cell Lymphoma
Interventions
Genetic: cemacabtagene ansegedleucel
Device: Foresight CLARITY™ IUO MRD test, powered by PhasED-Seq™
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.

In this study, participants with MRD are randomized 1:1 to treatment with cema-cel or an observation arm. Treatment includes cema-cel following a lymphodepletion regimen of fludarabine and cyclophosphamide.

Prior to August 2025, participants may also have received an anti-CD52 monoclonal antibody, ALLO-647, as part of their lymphodepletion regimen.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
250
Inclusion Criteria
  1. 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.
  2. 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.
  3. Participant achieved CR, or PR suitable for observation, at the end of first line therapy based on PET/CT evaluation
  4. Foresight CLARITY™ IUO MRD test, powered by PhasED-Seq™, is positive.
  5. Adult participants ≥18 years of age.
  6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
  7. Adequate hematological, renal, hepatic, pulmonary, and cardiac function
  8. Non-hematologic toxicities related to prior therapy must be recovered to baseline or grade ≤1.

Key

Exclusion Criteria
  1. 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.
  2. Prior treatment with anti-CD19 targeted therapies.
  3. Anti-cancer treatment, including radiation, after end of treatment PET/CT and/or MRD testing is performed.
  4. Active and clinically significant autoimmune disease.
  5. Active systemic bacterial, fungal, or viral infections requiring systemic treatment.
  6. 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
GroupInterventionDescription
cemacabtagene ansegedleucelcemacabtagene ansegedleucelParticipants receive cemacabtagene ansegedleucel following lymphodepletion regimen comprised of fludarabine and cyclophosphamide.
cemacabtagene ansegedleucelFludarabineParticipants receive cemacabtagene ansegedleucel following lymphodepletion regimen comprised of fludarabine and cyclophosphamide.
cemacabtagene ansegedleucelCyclophosphamideParticipants receive cemacabtagene ansegedleucel following lymphodepletion regimen comprised of fludarabine and cyclophosphamide.
cemacabtagene ansegedleucelForesight CLARITY™ IUO MRD test, powered by PhasED-Seq™Participants receive cemacabtagene ansegedleucel following lymphodepletion regimen comprised of fludarabine and cyclophosphamide.
ObservationForesight 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.
Primary Outcome Measures
NameTimeMethod
Event-free survival per independent review committee assessmentUp to 60 months
Secondary Outcome Measures
NameTimeMethod
Overall survivalUp to 60 months
Incidence and severity of adverse events and their relationship to cemacabtagene ansegedleucel and ALLO-647Up 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-647Up to 60 months

Change from baseline value and NCI toxicity grading of laboratory values outside of normal ranges using CTCAE version 5.0.

Progression-free survival per independent review committee assessmentUp to 60 months
Minimal residual disease clearanceUp to 60 months

Trial Locations

Locations (53)

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

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Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
Matthew Ulrickson, MD
Principal Investigator

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