Clinical trial NCT06500273: Consolidation of First-Line MRD+ Remission With Cema-cel in Patients With LBCL
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Large B-cell Lymphoma
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
ALLO-647
PMBCL
Consolidation
First-line
Front-line
Frontline
PhasED-Seq™
CLARITY™
Anti-CD52
AlloCAR T™
Lead sponsor: Allogene Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Foresight Diagnostics, Inc.
First posted: 2024-07-15
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Event-free survival per independent review committee assessment
timeFrame: Up to 60 months
Secondary outcomes:
measure: Progression-free survival per independent review committee assessment
timeFrame: Up to 60 months
measure: Overall survival
timeFrame: Up to 60 months
measure: Incidence and severity of adverse events and their relationship to cemacabtagene ansegedleucel and ALLO-647
timeFrame: Up to 60 months
measure: Incidence and severity of laboratory toxicities related to cemacabtagene ansegedleucel and ALLO-647
timeFrame: Up to 60 months
measure: Minimal residual disease clearance
timeFrame: Up to 60 months
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Berkeley
country: United States
facility: Alta Bates Summit Medical Center
state: California
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Sacramento
country: United States
facility: University of California, Davis Comprehensive Cancer Center
state: California
city: San Diego
country: United States
facility: University of California, San Diego
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Newark
country: United States
facility: Medical Oncology Hematology Consultants
state: Delaware
city: Washington
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
city: Miami
country: United States
facility: Miami Cancer Institute at Baptist Health, Inc.
state: Florida
city: Orlando
country: United States
facility: Advent Health Cancer Institute
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Augusta
country: United States
facility: Augusta University Georgia Cancer Center
state: Georgia
city: Indianapolis
country: United States
facility: Indiana Blood and Marrow Transplantation
state: Indiana
city: Kansas City
country: United States
facility: The University of Kansas Hospital
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky Medical Center
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville Health Brown Cancer Center
state: Kentucky
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine - Siteman Cancer Center
state: Missouri
city: East Brunswick
country: United States
facility: Astera Cancer Care
state: New Jersey
city: Hackensack
country: United States
facility: John Theurer Cancer Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: New York
country: United States
facility: Columbia University Irving Medical Center and New York-Presbyterian Hospital
state: New York
city: Durham
country: United States
facility: Duke Blood Cancer Center
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care - Kenwood
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Eugene
country: United States
facility: Oncology Associates of Oregon
state: Oregon
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology - Central South
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Dallas Fort Worth
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Texas Transplant Institute
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Tyler
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute, University of Utah
state: Utah
city: Salt Lake City
country: United States
facility: Intermountain Health LDS Hospital
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates - Norfolk
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
Study officials:
affiliation: Allogene Therapeutics, Inc.
name: Allogene Study Director
role: STUDY_DIRECTOR
References: