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A Study to Investigate the Efficacy and Safety of Sonrotoclax Plus Zanubrutinib Compared With Placebo Plus Zanubrutinib in Adults With Relapsed/Refractory Mantle Cell Lymphoma (CELESTIAL-RRMCL)

RecruitingPhase 3

A Phase 3 Randomized Double-Blind Multicenter Study of Sonrotoclax Plus Zanubrutinib Versus Placebo Plus Zanubrutinib in Patients With Relapsed/Refractory Mantle Cell Lymphoma

Who can join

Ages 18 and older · All sexes

Full eligibility criteria
Inclusion Criteria:

* Histologically locally confirmed diagnosis of MCL based on the World Health Organization 2022 classification of Haematolymphoid Tumors (WHO-HAEM5), or based on International Consensus Classification (ICC)
* Ability to provide archival or fresh tumor tissue for retrospective central confirmation of MCL diagnosis
* Received 1 to 5 prior lines of systemic therapy including an anti-CD20 monoclonal antibody (mAb)-based immunotherapy or chemoimmunotherapy and requiring treatment in the opinion of the investigator
* Relapsed or refractory disease after the last line of therapy
* Measurable disease defined as ≥ 1 nodal lesion that is \> 1.5 cm in longest diameter, or ≥ 1 extranodal lesion that is \> 1 cm in longest diameter
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2
* Adequate organ function

Exclusion Criteria:

* Prior therapy with B-cell lymphoma-2 inhibitor (BCL2i)
* Prior therapy with BTK degraders
* Prior therapy with covalent or non-covalent Bruton tyrosine kinase inhibitor (BTKi) unless the participant was intolerant of non-zanubrutinib covalent or non-covalent BTKi. Participants with refractory disease to BTKi therapy or relapse attributed to failure of BTKi therapy are ineligible.
* Prior autologous stem cell transplantation or chimeric antigen receptor T-cell therapy within 3 months before first dose of study drug
* Prior allogeneic stem cell transplant within 6 months of the first dose of the study drug
* Known central nervous system involvement by lymphoma
* Clinically significant cardiovascular disease
* History of stroke or intracranial hemorrhage within 6 months before first dose of study drug

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

About the study

The goal of this study is to compare how well sonrotoclax plus zanubrutinib works versus zanubrutinib plus placebo in treating adults with relapsed/refractory (R/R) mantle cell lymphoma (MCL). This study will also look at the safety of sonrotoclax plus zanubrutinib versus zanubrutinib plus placebo.

What is being tested

Sponsor: BeOne Medicines · Participants: 300 · Started: Mar 5, 2025

Contact the study team

Official record on ClinicalTrials.gov — NCT06742996

Locations in the U.S.

AlabamaUniversity of Alabama At Birmingham Hospital, Birmingham
ArizonaUniversity of Arizona Cancer Center, Tucson
CaliforniaUcsf Fresno, Fresno
Kaiser Permanente Southern California, Irvine
ConnecticutYale University Yale Cancer Center, New Haven
FloridaMemorial Cancer Institute, Memorial Healthcare System, Pembroke Pines
Cleveland Clinic Florida, Weston
IllinoisRush University Medical Center, Chicago
University of Chicago Medical Center, Chicago
IndianaFort Wayne Medical Oncology and Hematology, Fort Wayne
IowaMission Cancer and Blood, Waukee
LouisianaOur Lady of the Lake Hospital, Baton Rouge
MarylandThe University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore
MassachusettsDana Farber Cancer Institute Longwood Medical Center, Boston
MichiganUniversity of Michigan, Ann Arbor
The Cancer and Hematology Centers, Grand Rapids
MinnesotaMayo Clinic Rochester, Rochester
MississippiHattiesburg Hematology and Oncology Clinic, Hattiesburg
MissouriWashington University School of Medicine, St Louis
NebraskaNebraska Cancer Specialists St Francis Grand Island, Grand Island
Nebraska Cancer Specialists, Omaha
New JerseyThe Valley Hospital, Inc, Paramus
New YorkMemorial Sloan Kettering Cancer Center Mskcc, New York
North CarolinaAtrium Health Levine Cancer Institute (Lci), Charlotte
Duke University, Durham
Atrium Health Wake Forest Baptist, Winston-Salem
OhioCleveland Clinic Foundation, Cleveland
University Hospitals, Cleveland
Ohio Health Research Institute, Columbus
Ohio State University Comprehensive Cancer Center, Columbus
PennsylvaniaPenn State Milton S Hershey Medical Center, Hershey
McGlinn Cancer Institute, West Reading
TennesseeTennessee Oncology, Nashville
Tennessee Oncology Nashville St Thomas Midtown Clinic, Nashville
TexasMd Anderson Cancer Center, Houston
Texas Oncology Austin Midtown, Round Rock
VirginiaUniversity of Virginia, Charlottesville
Virgina Cancer Specialists, Gainesville
Vcu Massey Cancer Center, Richmond
WashingtonNorthwest Cancer Specialist, Pc(Us Oncology Research), Vancouver
WisconsinUniversity of Wisconsin, Madison

Conditions

From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.