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Trial record 1 of 1 for:    NCT02343120
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Study of the Safety and Pharmacokinetics of BGB-3111 in Subjects With B-Cell Lymphoid Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02343120
Recruitment Status : Completed
First Posted : January 21, 2015
Results First Posted : April 27, 2022
Last Update Posted : April 28, 2022
Sponsor:
Information provided by (Responsible Party):
BeiGene

Brief Summary:
This study evaluated the safety, tolerability, pharmacokinetic profile and efficacy of BGB-3111 in participants with B-cell lymphoid malignancies.

Condition or disease Intervention/treatment Phase
B-cell Malignancies Drug: Zanubrutinib Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 385 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II, Open-Label, Multiple-Dose, Dose Escalation and Expansion Study to Investigate the Safety and Pharmacokinetics of the BTK Inhibitor BGB-3111 in Subjects With B-Cell Lymphoid Malignancies
Actual Study Start Date : September 4, 2014
Actual Primary Completion Date : March 31, 2021
Actual Study Completion Date : March 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Zanubrutinib
Participants were administered up to 320 mg total daily dose of zanubrutinib until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up
Drug: Zanubrutinib
Oral administration by capsule
Other Names:
  • BGB-3111
  • Brukinsa




Primary Outcome Measures :
  1. Part 1 and Part 2: Number of Participants With Adverse Events [ Time Frame: Up to approximately 6 years and 7 months ]
    Number of participants with adverse events and serious adverse events, including clinically relevant physical examinations and laboratory measurements

  2. Part 1: Recommended Phase 2 Dose (RP2D) for Zanubrutinib [ Time Frame: Month 9 ]
    RP2D for zanubrutinib was the maximum tolerated dose (MTD) or less, which was determined by testing increasing doses up to 320 mg QD


Secondary Outcome Measures :
  1. Part 1 and Part 2: Area Under the Curve From Time 0 to the Last Sampling Time Point Within the Dose Interval (AUClast) of Zanubrutinib [ Time Frame: Week 1 Day 1 pre-dose, 0.5, 1, 2, 3, 4, and 8 hours ]
  2. Part 1 and Part 2: Area Under the Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Zanubrutinib [ Time Frame: Week 1 Day 1 pre-dose, 0.5, 1, 2, 3, 4, and 8 hours ]
  3. Part 1 and Part 2: Maximum Observed Plasma Concentration (Cmax) After Administration of Zanubrutinib [ Time Frame: Week 1 Day 1 pre-dose, 0.5, 1, 2, 3, 4, and 8 hours ]
  4. Part 1 and Part 2: Maximum Observed Plasma Concentration (Cmax) After Administration of Zanubrutinib [ Time Frame: Week 2 Day 1 pre-dose and 24 hours ]
  5. Part 1 and Part 2: Time to Maximum Observed Plasma Concentration (Tmax) of Zanubrutinib [ Time Frame: Week 1 Day 1 pre-dose, 0.5, 1, 2, 3, 4, and 8 hours ]
  6. Part 1 and Part 2: Time to Maximum Observed Plasma Concentration (Tmax) of Zanubrutinib [ Time Frame: Week 2 Day 1 pre-dose and 24 hours ]
  7. Part 1 and Part 2: Apparent Terminal Half-life (t1/2) of Zanubrutinib [ Time Frame: Week 1 Day 1 pre-dose, 0.5, 1, 2, 3, 4, and 8 hours ]
  8. Part 1 and Part 2: Apparent Clearance (CL/F) of Zanubrutinib [ Time Frame: Week 1 Day 1 pre-dose, 0.5, 1, 2, 3, 4, and 8 hours ]
  9. Part 1 and Part 2: Apparent Volume of Distribution of Zanubrutinib During the Terminal Phase (Vz/F) [ Time Frame: Week 1 Day 1 pre-dose, 0.5, 1, 2, 3, 4, and 8 hours ]
  10. Part 1 and Part 2: Overall Response Rate (ORR) [ Time Frame: Up to 6 years and 7 months ]
    ORR is defined as the percentage of participants with partial or complete response (CR), as assessed by the investigator. For CLL/SLL, ORR includes partial response (PR) with lymphocytosis (PR-L) or better (includes PR-L, PR, nodular PR or nPR and CR with incomplete marrow recovery or CRi) and for MW, ORR includes minor response or better. Efficacy results are reported for each of the B-cell malignancy subtypes: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), Waldenström macroglobulinemia (WM), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), Richter's Transformation (RT), and Hairy cell leukemia (HCL).

  11. Part 1 and Part 2: Complete Response Rate (CRR) [ Time Frame: Up to 6 years and 7 months ]
    CRR is defined as the percentage of participants who achieve a complete response, as assessed by the investigator. For CLL/SLL, CRR includes CRi or better. For WM, CRR includes very good partial response (VGPR) or better. Efficacy results are reported for each of the B-cell malignancy subtypes: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), Waldenström macroglobulinemia (WM), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), Richter's Transformation (RT), and Hairy cell leukemia (HCL).

  12. Part 1 and Part 2: Partial Response (PR) or Better [ Time Frame: Up to 6 years and 7 months ]
    PR or better is defined as the percentage of participants who achieve a partial response or better, as assessed by the investigator. For CLL/SLL, includes PR, nPR, CRi, CR and for WM includes PR, VGPR, and CR. Efficacy results are reported for the B-cell malignancy subtypes chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and Waldenström macroglobulinemia (WM).

  13. Part 1 and Part 2: Progression-free Survival (PFS) [ Time Frame: Up to 6 years and 7 months ]
    PFS is defined as the time from the first dose date of study drug to the date of the earliest occurrence of progressive disease or death due to any cause, whichever occurs first. Efficacy results are reported for each of the B-cell malignancy subtypes: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), Waldenström macroglobulinemia (WM), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), Richter's Transformation (RT), and Hairy cell leukemia (HCL).

  14. Part 1 and Part 2: Overall Survival (OS) [ Time Frame: Up to 6 years and 7 months ]
    OS is defined as the time from the date of the first dose to death due to any cause. Efficacy results are reported for each of the B-cell malignancy subtypes: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), Waldenström macroglobulinemia (WM), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), Richter's Transformation (RT), and Hairy cell leukemia (HCL).

  15. Part 1 and Part 2: Duration of Response (DOR) [ Time Frame: Up to 6 years and 7 months ]
    DOR for responders is defined as time from the date of the earliest qualifying response to the date of progressive disease or death for any cause, whichever occurs earlier. Efficacy results are reported for responders (defined as PR or better, except CLL/SLL and WM) in each of the B-cell malignancy subtypes: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; PR with lymphocytosis or better), Waldenstrom macroglobulinemia (WM; minor response or better), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), Richter's Transformation (RT), and Hairy cell leukemia (HCL).

  16. Number of Participants With Greater Than 75% Bruton's Tyrosine Kinase (BTK) Occupancy [ Time Frame: Week 1 Day 1 (W1D1) predose, W1D1 4 hours, W1D2 24 hours, W1D3 predose, and W2D1 predose ]
    Number of participants with greater than 75% BTK occupancy of zanubrutinib in peripheral blood mononuclear cells (PBMCs)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Aged ≥ 18 years, voluntarily consented to the study.
  2. WHO classification defined B-lymphoid malignancy, with the exception of Burkitt lymphoma/leukemia, plasma cell myeloma, acute lymphoblastic leukemia, lymphoblastic lymphoma, and plasmablastic lymphoma.
  3. Requirement for treatment in the opinion of the investigator.
  4. Disease which has relapsed, or is refractory, following at least one line of therapy, with no therapy of higher priority available.
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  6. Adequate hematologic function, as defined by neutrophils ≥ 1.0 x 10^9/L and platelets ≥ 50 x 10^9/L; participants with neutrophils < 1.0 x 10^9/L due to marrow infiltration are allowed to receive growth factors to bring pre-treatment neutrophils to ≥ 1.0 x 10^9/L.
  7. Adequate renal function, as defined by creatinine clearance of ≥ 30 ml/min (as estimated by the Cockcroft-Gault equation or as measured by nuclear medicine scan or 24 hour urine collection).
  8. Adequate liver function, as defined by aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN), and bilirubin ≤ 1.5 x ULN (unless documented Gilbert's syndrome).
  9. International normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (APTT) ≤ 1.5 x ULN.
  10. Female participants of childbearing potential and non-sterile males must practice at least one of the following methods of birth control with partner(s) throughout the study and for 90 days after discontinuing study drug: total abstinence from sexual intercourse, double-barrier contraception, IUD or hormonal contraceptive initiated at least 3 months prior to first dose of study drug.
  11. Male participants must not donate sperm from initial study drug administration, until 90 days after drug discontinuation.

Exclusion Criteria:

  1. Current central nervous system (CNS) involvement by disease
  2. Current histologically transformed disease.
  3. Prior Bruton's tyrosine kinase (BTK) inhibitor treatment.
  4. Allogeneic stem cell transplantation within 6 months, or has active graft-versus-host disease (GVHD) requiring ongoing immunosuppression.
  5. Receipt of the following treatment prior to first dose of zanubrutinib: corticosteroids given with anti-neoplastic intent within 7 days, chemotherapy or radiotherapy within 2 weeks, monoclonal antibody within 4 weeks.
  6. Not recovered from toxicity of any prior chemotherapy to grade ≤ 1.
  7. 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.
  8. Uncontrolled systemic infection requiring parenteral anti-microbial therapy.
  9. Major surgery in the past 4 weeks.
  10. Known HIV, or active hepatitis B or hepatitis C infection (detected positive by PCR).
  11. Cardiovascular disease resulting in New York Heart Association function status of ≥ 3.
  12. Significant active renal, neurologic, psychiatric, hepatic or endocrinologic disease that in the investigator's opinion would adversely impact on his/her participating in the study.
  13. Inability to comply with study procedures.
  14. On medications which are cytochrome P450 (CYP) 3A inhibitors.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02343120


Locations
Show Show 23 study locations
Sponsors and Collaborators
BeiGene
Investigators
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Study Director: Study Director BeiGene
  Study Documents (Full-Text)

Documents provided by BeiGene:
Study Protocol  [PDF] September 25, 2018
Statistical Analysis Plan  [PDF] October 19, 2018

Publications:
C.S. Tam M. Wang D. Simpson S. Opat G. Cull J. Munoz T.J. Phillips W. Kim S. Atwal R. Wei J. Huang R. Elstrom J. Trotman. UPDATED SAFETY AND EFFICACY DATA IN THE PHASE 1 TRIAL OF PATIENTS WITH MANTLE CELL LYMPHOMA (MCL) TREATED WITH BRUTON TYROSINE KINASE (BTK) INHIBITOR ZANUBRUTINIB (BGB-3111). Hematological Oncology. 2019; 37(S2) DOI: https://doi.org/10.1002/hon.55_2630

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: BeiGene
ClinicalTrials.gov Identifier: NCT02343120    
Other Study ID Numbers: BGB-3111-AU-003
2016-003364-39 ( EudraCT Number )
First Posted: January 21, 2015    Key Record Dates
Results First Posted: April 27, 2022
Last Update Posted: April 28, 2022
Last Verified: April 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms
Zanubrutinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action