Clinical Trials/NCT03520920

NCT03520920

Completed

Phase 2

A Phase 2 Study to Assess the Safety, Tolerability, and Activity of BGB-3111 in Combination With Rituximab in Chinese Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (Non-GCB Subtype) and Relapsed/Refractory Indolent Lymphoma (Follicular Lymphoma and Marginal Zone Lymphoma)

BeiGene4 sites in 1 country41 target enrollmentJanuary 4, 2018

ConditionsMarginal Zone Lymphoma Follicular Lymphoma Diffuse Large B-Cell Lymphoma

InterventionsZanubrutinib Rituximab

DrugsZanubrutinib Rituximab

Overview

Phase: Phase 2
Intervention: Zanubrutinib
Conditions: Marginal Zone Lymphoma
Sponsor: BeiGene
Enrollment: 41
Locations: 4
Primary Endpoint: Overall Response Rate (ORR) As Measured By The Investigator
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This was a multicenter, open-label, phase 2 study to evaluate efficacy, safety, and tolerability of BGB-3111 (zanubrutinib) 160 milligrams (mg) twice daily (BID) in combination with rituximab in Chinese participants with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) (non-GCB [non-germinal center B-cell-like] subtype) and R/R indolent lymphoma (follicular lymphoma [FL] and marginal zone lymphoma [MZL]).

Registry

clinicaltrials.gov

Start Date

January 4, 2018

End Date

August 28, 2020

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

BeiGene

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•≥ Age 18 years at time of signing of informed consent.
•Measurable disease by computed tomography (CT) or positron emission tomography/CT or magnetic resonance imaging, defined as ≥1 nodal lesion that was \>1.5 centimeters (cm) in the longest diameter, or ≥1 extra-nodal lesion (for example, hepatic nodules) that was \>1 cm in the longest diameter.
•Availability of archival or fresh tumor tissue sample from an evaluable core or excisional biopsy.
•Participants meet the following criteria:
•Cohort 1: R/R non-GCB DLBCL i. Histologically confirmed non-GCB DLBCL per Hans criteria with non-transformed disease; additional methodologies for confirming non-GCB DLBCL may have been considered in consultation with the medical monitor. ii. Relapsed disease (disease progression after most recent therapy for DLBCL occurring more than 6 months after the completion of last therapy) or refractory disease (failure to achieve complete response \[CR\] or partial response \[PR\] to therapy for non-GCB DLBCL or disease progression within 6 months after completion of the most recent therapy for non-GCB DLBCL). iii. Must have received at least one standard anthracycline ± rituximab-based treatment (for example, rituximab plus cyclophosphamide, doxorubicin \[or epirubicin, hydroxydaunorubicin, or similar\], vincristine, and prednisone) or cyclophosphamide, vincristine, and prednisone +/- rituximab for DLBCL.
•Cohort 2: R/R FL or R/R MZL i. Histologically confirmed CD20+ FL (Grade 1, 2, or 3a) or MZL. ii. Relapsed disease (disease progression after most recent therapy for FL or MZL occurring more than 6 months after the completion of last therapy) or refractory disease (failure to achieve complete response (CR) or partial response (PR) to most recent therapy for FL or MZL, or disease progression within 6 months after completion of the most recent therapy for FL or MZL).
•Laboratory parameters as specified below:
•Hematologic: Platelet count ≥75 x 10\^9/liter (L) independent of growth factor or transfusion within 7 days of study entry; absolute neutrophil count (ANC) ≥1 x 10\^9/L independent of growth factor within 7 days of study entry, hemoglobin \>8 grams/deciliter within 7 days of study entry.
•Hepatic: Total bilirubin ≤ 2x upper limit of normal (ULN) unless documented Gilbert's syndrome; aspartate aminotransferase/serum glutamic-oxaloacetic transaminase and alanine transaminase/serum glutamic-pyruvic transaminase ≤3x ULN.
•Renal: Creatinine clearance ≥30 milliliters/minute (as estimated by the Cockcroft-Gault equation based on ideal body weight or as measured by nuclear medicine scan or 24-hour urine collection).

Exclusion Criteria

•Known central nervous system lymphoma or leukemia.
•Histological confirmed gastric mucosa-associated lymphoid tissue type MZL.
•Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.
•Clinically significant cardiovascular disease.
•History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention.
•History of stroke or intracranial hemorrhage within 6 months before first dose of study drug.
•Severe or debilitating pulmonary disease.
•Hypersensitivity reaction to zanubrutinib or rituximab or any of the other ingredients of the study drugs.
•Prior Bruton tyrosine kinase inhibitor treatment.
•Required ongoing treatment with a strong cytochrome P450 protein inhibitor or inducer.

Arms & Interventions

R/R Non-GCB DLBCL

Participants with non-GCB DLBCL received zanubrutinib plus rituximab for up to progressive disease or intolerance.

Intervention: Zanubrutinib

R/R Non-GCB DLBCL

Participants with non-GCB DLBCL received zanubrutinib plus rituximab for up to progressive disease or intolerance.

Intervention: Rituximab

R/R FL or MZL

Participants with R/R FL or MZL received zanubrutinib plus rituximab for up to progressive disease or intolerance.

Intervention: Zanubrutinib

R/R FL or MZL

Participants with R/R FL or MZL received zanubrutinib plus rituximab for up to progressive disease or intolerance.

Intervention: Rituximab

Outcomes

Primary Outcomes

Overall Response Rate (ORR) As Measured By The Investigator

Time Frame: Up to approximately 2.5 years

The percentage of participants whose best overall response met partial response (PR) or complete response (CR) criteria among all participants. The 95% confidence interval (CI) was calculated with the Clopper-Pearson method.

Secondary Outcomes

Progression-free Survival (PFS) As Determined By Investigator(Up to approximately 2.5 years)
OS: Survival Rate(Up to approximately 2.5 years)
Duration Of Response (DOR) As Determined By Investigator(Up to approximately 2.5 years)
DOR: Event-free Rate(Up to approximately 2.5 years)
Overall Survival (OS)(Up to approximately 2.5 years)
PFS: Event-free Rate(Up to approximately 2.5 years)
Time To Response (TTR) As Determined By The Investigator(Up to approximately 2.5 years)
Median TTR(Up to approximately 2.5 years)
Complete Response Rate As Determined By The Investigator(Up to approximately 2.5 years)
Number Of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) And Serious TEAEs(Up to approximately 2.5 years)