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Study of BTK Inhibitor Zanubrutinib in Participants With Relapsed/Refractory Non-GCB Type Diffuse Large B Cell Lymphoma

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ClinicalTrials.gov Identifier: NCT03145064
Recruitment Status : Completed
First Posted : May 9, 2017
Results First Posted : November 8, 2021
Last Update Posted : November 8, 2021
Sponsor:
Information provided by (Responsible Party):
BeiGene

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Condition Diffuse Large B-cell Lymphoma
Intervention Drug: Zanubrutinib
Enrollment 41
Recruitment Details This study was conducted at 11 centers in China, all of which enrolled participants. The first participant was dosed on 30 June 2017. Since the primary and secondary objectives were met and the analysis was complete, the sponsor ended the study on 03 September 2020 (Last patient last visit). As of the final database lock (15 October 2020), 41 participants were enrolled and treated with zanubrutinib.
Pre-assignment Details  
Arm/Group Title Zanubrutinib
Hide Arm/Group Description Participants received 160 milligrams (mg) of zanubrutinib twice daily (BID).
Period Title: Overall Study
Started 41
Received At Least 1 Dose of Study Drug 41
Completed 0
Not Completed 41
Reason Not Completed
Death             24
Lost to Follow-up             3
Withdrawal by Subject             6
Study ended by sponsor once primary/ secondary analysis was complete and participants discontinued             4
Other: Transferred to Long term Extension (LTE) study BGB-3111-LTE1 (NCT04170283)             4
Arm/Group Title Zanubrutinib
Hide Arm/Group Description Participants received 160 mg of zanubrutinib BID.
Overall Number of Baseline Participants 41
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 41 participants
57.2  (12.45)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants
Female
16
  39.0%
Male
25
  61.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants
American Indian or Alaska Native
0
   0.0%
Asian
41
 100.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
0
   0.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Eastern Cooperative Oncology Group Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants
Grade 0
10
  24.4%
Grade 1
27
  65.9%
Grade 2
4
   9.8%
[1]
Measure Description: Grade 0 : Fully active, able to carry on all pre-disease performance without restriction; Grade 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, eg, light house work, office work; Grade 2: Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours; Lower grades indicate better outcome.
Hepatitis B Core Antibody   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants
Positive
13
  31.7%
Negative
28
  68.3%
[1]
Measure Description: All positive participants were undetectable for hepatitis B virus DNA assessment.
1.Primary Outcome
Title Overall Response Rate
Hide Description Overall response rate was defined as the percentage of participants achieving either a partial response (PR) or complete response (CR) as determined by investigator according to the 2014 modification of the International Working Group (IWG) in Non-Hodgkin's lymphoma (NHL) Criteria.
Time Frame Up to approximately 23 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Analysis Set, which included all participants who received any dose of study drug, was the analysis set used for the efficacy and safety analyses.
Arm/Group Title Zanubrutinib
Hide Arm/Group Description:
Participants received 160 mg of zanubrutinib BID.
Overall Number of Participants Analyzed 41
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
29.3
(16.13 to 45.54)
2.Secondary Outcome
Title Progression-free Survival
Hide Description Progression-free survival was defined as the time from first dose of zanubrutinib until first documentation of progression (by IWG on NHL criteria) or death, whichever occurred first.
Time Frame Up to 3 years and 2 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Analysis Set, which included all participants who received any dose of study drug, was the analysis set used for the efficacy and safety analyses
Arm/Group Title Zanubrutinib
Hide Arm/Group Description:
Participants received 160 mg of zanubrutinib BID.
Overall Number of Participants Analyzed 41
Median (95% Confidence Interval)
Unit of Measure: months
2.8
(2.56 to 5.45)
3.Secondary Outcome
Title Duration Of Response
Hide Description Duration of response was defined as the time from the date that the response criteria were first met to the date that progressive disease was objectively documented or death, whichever occurred first. Duration of response was summarized for responders (with a best overall response of CR or PR) only.
Time Frame Up to 3 years and 2 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Analysis Set, which included all participants who received any dose of study drug, was the analysis set used for the efficacy and safety analyses
Arm/Group Title Zanubrutinib
Hide Arm/Group Description:
Participants received 160 mg of zanubrutinib BID.
Overall Number of Participants Analyzed 12
Median (95% Confidence Interval)
Unit of Measure: months
4.5 [1] 
(2.14 to NA)
[1]
NA = Not estimable due to insufficient number of participants with events
4.Secondary Outcome
Title Time To Response
Hide Description Time to response was defined as the time from the first dose of zanubrutinib to the documentation of first response. Time to response was summarized for responders (with a best overall response of CR or PR) only.
Time Frame Up to 3 years and 2 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Analysis Set, which included all participants who received any dose of study drug, was the analysis set used for the efficacy and safety analyses.
Arm/Group Title Zanubrutinib
Hide Arm/Group Description:
Participants received 160 mg of zanubrutinib BID.
Overall Number of Participants Analyzed 12
Median (Full Range)
Unit of Measure: months
2.83
(2.6 to 3.2)
5.Secondary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Hide Description A treatment-emergent adverse event was defined as an adverse event that had an onset date or a worsening in severity from baseline (pretreatment) on or after the date of first dose of study drug up to 30 days following study drug discontinuation (Safety Follow-up Visit) or initiation of new anticancer therapy, whichever occurred first.
Time Frame From the time of informed consent to 30 days after the last dose of study drug (approximately Up to 3 years and 2 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Analysis Set included all participants who received any dose of study drug.
Arm/Group Title Zanubrutinib
Hide Arm/Group Description:
Participants received 160 milligrams (mg) of zanubrutinib twice daily (BID).
Overall Number of Participants Analyzed 41
Measure Type: Number
Unit of Measure: Participants
Participants with at least1 TEAE 36
Serious TEAE 12
TEAE leading to treatment discontinuation 4
6.Other Pre-specified Outcome
Title Overall Survival
Hide Description Overall survival was defined as the time from first dose of zanubrutinib until death due to any cause.
Time Frame Up to 3 years and 2 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Analysis Set, which included all participants who received any dose of study drug, was the analysis set used for the efficacy and safety analyses.
Arm/Group Title Zanubrutinib
Hide Arm/Group Description:
Participants received 160 mg of zanubrutinib BID.
Overall Number of Participants Analyzed 41
Median (95% Confidence Interval)
Unit of Measure: months
8.4 [1] 
(4.8 to NA)
[1]
NA = Not estimable due to insufficient number of participants with events
Time Frame From the time of informed consent to 30 days after the last dose of study drug (approximately up to 3 years and 2 months).
Adverse Event Reporting Description A treatment-emergent adverse event was defined as an adverse event that had an onset date or a worsening in severity from baseline (pretreatment) on or after the date of first dose of study drug up to 30 days following study drug discontinuation (Safety Follow-up Visit) or initiation of new anticancer therapy, whichever occurred first.
 
Arm/Group Title Zanubrutinib
Hide Arm/Group Description Participants received 160 mg of zanubrutinib BID.
All-Cause Mortality
Zanubrutinib
Affected / at Risk (%)
Total   24/41 (58.54%) 
Hide Serious Adverse Events
Zanubrutinib
Affected / at Risk (%)
Total   12/41 (29.27%) 
Ear and labyrinth disorders   
Sudden hearing loss  1  1/41 (2.44%) 
Eye disorders   
Cataract  1  1/41 (2.44%) 
Gastrointestinal disorders   
Abdominal pain  1  1/41 (2.44%) 
Intestinal obstruction  1  1/41 (2.44%) 
General disorders   
Death  1  2/41 (4.88%) 
Gait inability  1  1/41 (2.44%) 
Hepatobiliary disorders   
Liver injury  1  1/41 (2.44%) 
Infections and infestations   
Pneumonia  1  3/41 (7.32%) 
Abdominal infection  1  1/41 (2.44%) 
Herpes zoster  1  1/41 (2.44%) 
Otitis media chronic  1  1/41 (2.44%) 
Urinary tract infection  1  1/41 (2.44%) 
Metabolism and nutrition disorders   
Metabolic acidosis  1  1/41 (2.44%) 
Musculoskeletal and connective tissue disorders   
Back pain  1  1/41 (2.44%) 
1
Term from vocabulary, MedDRA 23.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Zanubrutinib
Affected / at Risk (%)
Total   34/41 (82.93%) 
Blood and lymphatic system disorders   
Anaemia  1  3/41 (7.32%) 
Leukopenia  1  3/41 (7.32%) 
Lymph node pain  1  2/41 (4.88%) 
Ear and labyrinth disorders   
Tinnitus  1  2/41 (4.88%) 
Gastrointestinal disorders   
Constipation  1  4/41 (9.76%) 
Diarrhoea  1  4/41 (9.76%) 
General disorders   
Influenza like illness  1  2/41 (4.88%) 
Malaise  1  2/41 (4.88%) 
Oedema peripheral  1  2/41 (4.88%) 
Infections and infestations   
Urinary tract infection  1  4/41 (9.76%) 
Pneumonia  1  3/41 (7.32%) 
Upper respiratory tract infection  1  3/41 (7.32%) 
Nasopharyngitis  1  2/41 (4.88%) 
Skin infection  1  2/41 (4.88%) 
Investigations   
Neutrophil count decreased  1  9/41 (21.95%) 
Platelet count decreased  1  5/41 (12.20%) 
Blood creatinine increased  1  4/41 (9.76%) 
Lymphocyte count decreased  1  4/41 (9.76%) 
White blood cell count decreased  1  4/41 (9.76%) 
Alanine aminotransferase increased  1  3/41 (7.32%) 
Aspartate aminotransferase increased  1  3/41 (7.32%) 
Weight decreased  1  3/41 (7.32%) 
Blood alkaline phosphatase increased  1  2/41 (4.88%) 
Blood bilirubin increased  1  2/41 (4.88%) 
Metabolism and nutrition disorders   
Hypokalaemia  1  7/41 (17.07%) 
Decreased appetite  1  2/41 (4.88%) 
Hyperglycaemia  1  2/41 (4.88%) 
Hypertriglyceridaemia  1  2/41 (4.88%) 
Hyperuricaemia  1  2/41 (4.88%) 
Hypoalbuminaemia  1  2/41 (4.88%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  3/41 (7.32%) 
Back pain  1  3/41 (7.32%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  4/41 (9.76%) 
Skin and subcutaneous tissue disorders   
Rash  1  4/41 (9.76%) 
Rash maculo-papular  1  2/41 (4.88%) 
Vascular disorders   
Hypertension  1  4/41 (9.76%) 
1
Term from vocabulary, MedDRA 23.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
BeiGene has 18 months from the end of the study at all sites to publish overall study results. After the 1st multi-site publication or the expiration of publication period, Investigators are free to publish/present the results of the study. Investigators must submit all draft publications/presentations to us for review 60 days prior to the planned publication/presentation date. BeiGene may request deletion of its confidential information & may request a further delay to protect its IP rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: BeiGene
Phone: +1-877-828-5568
EMail: clinicaltrials@beigene.com
Publications:
Yang H, Xiang B, Song Y, Zhang H, Zhao W, Zou D, Lv F, Bai O, Liu A, Li C, Tan Z, Wang W, Gui H, Novotny W, Huang J, Li Y. Zanubrutinib monotherapy for patients with relapsed or refractory non-germinal center diffuse large B-cell lymphoma: results from a phase II, single-arm, multicenter, study. American Society of Clinical Oncology. 2020
Layout table for additonal information
Responsible Party: BeiGene
ClinicalTrials.gov Identifier: NCT03145064    
Other Study ID Numbers: BGB-3111-207
CTR20170091 ( Registry Identifier: Center for drug evaluation, CFDA )
First Submitted: May 5, 2017
First Posted: May 9, 2017
Results First Submitted: August 31, 2021
Results First Posted: November 8, 2021
Last Update Posted: November 8, 2021