Large B-cell Lymphoma
Conditions
Keywords
Diffuse large B-cell lymphoma, DLBCL, Primary mediastinal B-cell lymphoma, LBCL, High grade B-cell lymphoma, HGBCL, Double-hit lymphoma, High-risk lymphoma, Minimal Residual Disease, MRD, CAR T, Allogeneic CAR T, CD19, cema-cel, cemacabtagene ansegedleucel, PMBCL, Consolidation, First-line, Front-line, Frontline, PhasED-Seq™, CLARITY™, AlloCAR T™
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.
Interventions
GENETICcemacabtagene ansegedleucel
An allogeneic CAR T cell therapy targeting CD19
DRUGFludarabine
Chemotherapy for lymphodepletion
DRUGCyclophosphamide
Chemotherapy for lymphodepletion
DEVICEForesight CLARITY™ IUO MRD test, powered by PhasED-Seq™
A diagnostic test intended to identify patients with minimal residual disease at the end of first line treatment for LBCL.
Sponsors
Allogene Therapeutics
Foresight Diagnostics, Inc.
Natera, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Event-free survival per independent review committee assessment | Up to 60 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
Countries
Australia, Canada, South Korea, United States
Contacts
CONTACTAllogene Therapeutics, Inc
STUDY_DIRECTORAllogene Study Director
Allogene Therapeutics, Inc.
Outcome results
None listed