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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

Tracking Information
First Submitted Date  ICMJE May 5, 2017
First Posted Date  ICMJE May 9, 2017
Results First Submitted Date  ICMJE August 31, 2021
Results First Posted Date  ICMJE November 8, 2021
Last Update Posted Date November 8, 2021
Actual Study Start Date  ICMJE June 30, 2017
Actual Primary Completion Date May 24, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 11, 2021)
Overall Response Rate [ Time Frame: Up to approximately 23 months ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 5, 2017)
Rate of objective response [ Time Frame: up to 3 years ]
The achievement of either a partial response (PR) or complete response (CR)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 11, 2021)
  • Progression-free Survival [ Time Frame: Up to 3 years and 2 months ]
    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.
  • Duration Of Response [ Time Frame: Up to 3 years and 2 months ]
    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 To Response [ Time Frame: Up to 3 years and 2 months ]
    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.
  • Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ 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) ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 5, 2017)
  • Progression free survival (PFS) [ Time Frame: up to 3 years ]
    Defined as time from first dose of BGB-3111 until first documentation of Progression (by IWG on NHL criteria) or death, whichever comes first
  • Duration of response (DOR) [ Time Frame: up to 3 years ]
    Defined as the time from the date that the response criteria are first met to the date that progressive disease (PD) is objectively documented or death, whichever occurs first.
  • Time to response (TTR) [ Time Frame: up to 3 years ]
    Defined as the time from first dose of BGB-3111 to documentation of a response.
Current Other Pre-specified Outcome Measures
 (submitted: October 11, 2021)
Overall Survival [ Time Frame: Up to 3 years and 2 months ]
Overall survival was defined as the time from first dose of zanubrutinib until death due to any cause.
Original Other Pre-specified Outcome Measures
 (submitted: May 5, 2017)
Overall survival (OS) [ Time Frame: up to 3 years ]
Defined as the time from first dose of BGB-3111 until death.
 
Descriptive Information
Brief Title  ICMJE Study of BTK Inhibitor Zanubrutinib in Participants With Relapsed/Refractory Non-GCB Type Diffuse Large B Cell Lymphoma
Official Title  ICMJE A Phase 2, Single Arm, Multicenter, Open-label Study of Bruton's Tyrosine Kinase (BTK) Inhibitor BGB-3111 in Subjects With Relapsed/Refractory Non-GCB Type Diffuse Large B Cell Lymphoma
Brief Summary Screening (up to 28 days); daily treatment until disease progression, unacceptable toxicity or death, withdrawal of consent, lost to follow-up, or study termination from sponsor; treatment (up to 2 years), safety follow-up (30 days); survival follow-up until data cutoff for final analysis.
Detailed Description

This is a single-arm, multicenter, open-label Phase 2 study to evaluate efficacy, safety, tolerability of BGB-3111 (zanubrutinib) in participants with relapsed/refractory non-germinal center B-cell (GCB) type diffuse large B-cell lymphoma (DLBCL).

The study will enroll approximately 40 participants treated with zanubrutinib (160 milligrams [mg]) twice daily (BID). All participants in the study were treated until disease progression, unacceptable toxicity, death, withdrawal of consent, or the study was terminated by the sponsor for final analysis. At the time of final analysis, participants who remained on treatment were considered for participation in the extension study when eligible. A treatment cycle consisted of 28 days.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Diffuse Large B-cell Lymphoma
Intervention  ICMJE Drug: Zanubrutinib
Administered at a dose of 160 mg BID orally.
Other Names:
  • BGB-3111
  • BRUKINSA
Study Arms  ICMJE Experimental: Zanubrutinib
Participants received zanubrutinib BID.
Intervention: Drug: Zanubrutinib
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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 5, 2018)
41
Original Estimated Enrollment  ICMJE
 (submitted: May 5, 2017)
100
Actual Study Completion Date  ICMJE September 3, 2020
Actual Primary Completion Date May 24, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  1. Histologically confirmed non-germinal center DLBCL, by immunohistochemistry using the Hans algorithm:

    1. Cluster of differentiation 10 (CD10)- and B-cell lymphoma 6 protein (BCL6)-,
    2. CD10-, BCL6+, but maximal unique match+
  2. Men and women ≥ 18 years of age.
  3. Eastern Cooperative Oncology Group performance status of 0-2.
  4. Measurable disease was defined as at least 1 lymph node > 1.5 centimeters in longest diameter and measurable in 2 perpendicular dimensions.
  5. All participants must have provided fresh tumor biopsy or recent tumor tissue samples (within 2 years of study entry [informed consent form signed]).
  6. Received at least one prior therapy for DLBCL that included anthracycline-based chemotherapy.
  7. Participant not eligible for or refused intensive chemotherapy and hematopoietic stem cell transplant.
  8. Documented failure to achieve at least partial response with, or documented disease progression after response to, the most recent treatment regimen.
  9. Neutrophils ≥ 1 x 10^9/liter (L) independent of growth factor support within 7 days of study entry.
  10. Platelets ≥ 75 x 10^9/L, independent of growth factor support or transfusion within 7 days of study entry.
  11. Creatinine clearance of ≥ 30 milliliters/minute (as estimated by the Cockcroft-Gault equation or estimated glomerular filtration rate).
  12. Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x upper limit of normal (ULN).
  13. Bilirubin ≤ 2 x ULN (unless documented Gilbert's syndrome), then up to 5 x ULN allowed.
  14. Independent of erythropoietin support or transfusion within 7 days of first dose of study drug.
  15. International normalized ratio ≤ 1.5 and activated partial thromboplastin time ≤ 1.5 x ULN.
  16. Participants may be enrolled who relapsed after autologous stem cell transplant if they are at least 6 months after transplant, participants should have had no active infections (that is, fungal or viral).
  17. Females of childbearing potential must have agreed to use highly effective forms of birth control throughout the course of the study and at least up to 90 days after last dose of study drug. Highly effective forms of birth control were defined as abstinence, hysterectomy, bilateral oophorectomy with no menstrual bleeding for up to 6 months, intrauterine contraception, hormonal methods such as contraceptive injection, oral contraceptive. Males must have undergone sterilization-vasectomy, or utilized a barrier method where the female partner utilized the effective forms of birth control noted above.
  18. Life expectancy of > 3 months.
  19. Able to provide written informed consent and could understand and comply with the requirements of the study.

Key Exclusion Criteria:

  1. Current or history of central nervous system lymphoma.
  2. Prior exposure to a BTK inhibitor.
  3. Prior corticosteroids (at dosages equivalent to prednisone > 20 mg/day) given with anti-neoplastic intent within 7 days, prior chemotherapy, targeted therapy, or radiation therapy within 3 weeks, or antibody-based therapies or Chinese anti-cancer herbal therapies within 4 weeks of the start of study drug.
  4. Major surgery within 4 weeks of screening.
  5. Toxicity of ≥ Grade 2 from prior anti-cancer therapy (except for alopecia, absolute neutrophil count [ANC]) and platelets. For ANC and platelets, please follow inclusion criteria #9 [neutrophils] and #10 [platelets]).
  6. History of other active malignancies within 2 years of study entry, with exception of (1) adequately treated in-situ carcinoma of cervix; (2) localized basal cell or squamous cell carcinoma of skin; (3) previous malignancy confined and treated locally (surgery or other modality) with curative intent.
  7. Currently active clinically significant cardiovascular disease such as uncontrolled arrhythmia, congestive heart failure, any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or history of myocardial infarction within 6 months of screening. Left ventricular ejection fraction is lower than 50% measured by echocardiography.
  8. QTcF (Fridericia's correction) > 450 milliseconds or other significant electrocardiogram abnormalities including second degree atrioventricular (AV) block Type II, or third-degree AV block.
  9. Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
  10. Uncontrolled systemic infection or infection requiring parenteral anti-microbial therapy.
  11. Known human immunodeficiency virus, or active hepatitis B or hepatitis C infection (detected positive by polymerase chain reaction).
  12. Pregnant or lactating women.
  13. Any life-threatening illness, medical condition or organ system dysfunction, which, in the investigator's opinion, could compromise the participant's safety, or put the study at risk.
  14. On medications that were strong cytochrome P450 (CYP), family 3, subfamily A (CYP3A) inhibitors or CYP3A inducers.

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Gender Based Eligibility: Yes
Gender Eligibility Description: male and female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03145064
Other Study ID Numbers  ICMJE BGB-3111-207
CTR20170091 ( Registry Identifier: Center for drug evaluation, CFDA )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Responsible Party BeiGene
Study Sponsor  ICMJE BeiGene
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Study Director BeiGene
PRS Account BeiGene
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP