A Randomized, Open-Label Study Evaluating The Efficacy And Safety Of Cemacabtagene Ansegedleucel In Participants With Minimal Residual Disease After Response To First Line Therapy For Large B-Cell Lymphoma (Alpha3)
Study on Treatment for Large B-Cell Lymphoma
Varun Mittal
Primary Investigator
Brief description of study
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.
Detailed description of study
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.
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Large B-Cell Lymphoma, Cancer
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Age: 18 years - 100 years
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Gender: All
Key Eligibility Criteria
Inclusion:
• LBCL histologically confirmed, per WHO 2017, by pathology report with one of the
listed histologies AND with at least one of the listed clinical criteria:
− Histologies (one of the following):
o Diffuse LBCL (DLBCL) not otherwise specified, Epstein-Barr
virus-positive (EBV+) DLBCL, DLBCL with IRF4/MUM1 rearrangement,
o High-grade B-cell lymphoma not otherwise specified, or with MYC and
BCL2 and/or BCL6 rearrangements,
o Primary mediastinal B-cell lymphoma.
− Clinical criteria (at least one of the following):
o International prognostic index (IPI) score of 2 to 5 at diagnosis,
o Ann Arbor Stage III or Stage IV disease at diagnosis,
o Ann Arbor Stage I or II disease at diagnosis with history of an equivocal
response (e.g., partial metabolic response) at interim or end of therapy
PET/CT.
• Blood sample was collected for ctDNA-based MRD testing between 3 and 8 weeks (± 2
weeks) after EOT of 1L therapy and MRD assay result was positive.
• Per the Lugano criteria 2014 (Cheson 2014), participant achieved CR, or PR suitable
for observation at the end of 1L therapy based on PET/CT evaluation after last
treatment (e.g., dose of chemotherapy, fraction of radiation) and remains in response on
PET/CT within 5 weeks of randomization. Repeat PET/CT is not required if initial end
of therapy PET/CT was performed within 5 weeks of randomization.
• Adult participants ≥18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• Adequate hematological, renal, liver, and cardiac function as per prespecified criteria.
Exclusion:
• LBCL includes history of CNS involvement (primary of secondary) or has arisen or
transformed from other malignancy (e.g., transformed follicular lymphoma or marginal
zone lymphoma, Richter’s transformation). Additionally, T-cell/histiocyte rich LBCL is
excluded.
• Prior treatment with anti-CD19 targeted therapies.
• Any anti-cancer treatment after MRD sample collection.
• Participants with active systemic bacterial, fungal, or viral infection requiring systemic
treatment.
• Any other active malignancies that have required systemic treatment within 3 years
prior to enrollment.
• Participants unwilling to undergo an extended safety monitoring period (up to 15 years
after cema-cel infusion).
This study investigates the use of an investigational medication in patients with large B-cell lymphoma (LBCL) who have minimal residual disease after completing first-line therapy. Large B-cell lymphoma is a type of cancer that affects white blood cells. The purpose of this study is to compare the effects of a treatment called cemacabtagene ansegedleucel, which is a type of cell therapy, with standard observation in these patients.
Participants in the study will be randomly assigned to one of two study arms: one receiving the investigational treatment and the other under observation. Those in the treatment arm will receive the investigational medication following a preparation regimen that includes specific drugs to help the body accept the treatment. This study will help understand the safety and effectiveness of this new approach compared to standard care.
- Who can participate: Adults aged 18 and older with confirmed large B-cell lymphoma who have completed first-line therapy and have minimal residual disease can participate. Participants must have good overall health and meet specific clinical criteria.
- Study details: Participants will be assigned to either receive the investigational treatment or be in an observation arm. The investigational treatment involves a specific type of cell therapy following a preparation regimen. Participants need to be willing to undergo long-term safety monitoring.
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