Consolidation of First-Line MRD+ Remission With Cema-cel in Patients With LBCL (ALPHA3)

Allogene Therapeutics

Status and phase: Enrolling; Phase 2

Conditions: Large B-cell Lymphoma

Treatments: Genetic: cemacabtagene ansegedleucel; Drug: Fludarabine; Device: Foresight CLARITY™ IUO MRD test, powered by PhasED-Seq™; Drug: Cyclophosphamide; Biological: ALLO-647

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT06500273

ALLO-501A-202

Details and patient eligibility

About

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.

Enrollment: 250 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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 (e.g., HIV).
6. History of another primary malignancy or bone marrow disorder (e.g., myelofibrosis, smoldering multiple myeloma) within 3 years prior to enrollment.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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250 participants in 3 patient groups

cemacabtagene ansegedleucel, ALLO-647

Experimental group

Description:

Participants receive cemacabtagene ansegedleucel following lymphodepletion regimen comprised of fludarabine, cyclophosphamide, and ALLO-647.

Treatment:

Biological: ALLO-647

Drug: Cyclophosphamide

Device: Foresight CLARITY™ IUO MRD test, powered by PhasED-Seq™

Drug: Fludarabine

Genetic: cemacabtagene ansegedleucel

cemacabtagene ansegedleucel

Experimental group

Description:

Participants receive cemacabtagene ansegedleucel following lymphodepletion regimen comprised of fludarabine and cyclophosphamide.

Treatment:

Drug: Cyclophosphamide

Device: Foresight CLARITY™ IUO MRD test, powered by PhasED-Seq™

Drug: Fludarabine

Genetic: cemacabtagene ansegedleucel

Observation

Other group

Description:

Participants do not receive any study treatments. They are observed as per the current standard of care.

Treatment:

Device: Foresight CLARITY™ IUO MRD test, powered by PhasED-Seq™