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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT02343120
Registration number
NCT02343120
Ethics application status
Date submitted
9/01/2015
Date registered
21/01/2015
Date last updated
28/04/2022
Titles & IDs
Public title
Study of the Safety and Pharmacokinetics of BGB-3111 in Subjects With B-Cell Lymphoid Malignancies
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Scientific 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
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Secondary ID [1]
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2016-003364-39
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Secondary ID [2]
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BGB-3111-AU-003
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
B-cell Malignancies
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Condition category
Condition code
Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Zanubrutinib
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
Treatment: Drugs: Zanubrutinib
Oral administration by capsule
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Part 1 and Part 2: Number of Participants With Adverse Events
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Assessment method [1]
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Number of participants with adverse events and serious adverse events, including clinically relevant physical examinations and laboratory measurements
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Timepoint [1]
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Up to approximately 6 years and 7 months
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Primary outcome [2]
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Part 1: Recommended Phase 2 Dose (RP2D) for Zanubrutinib
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Assessment method [2]
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RP2D for zanubrutinib was the maximum tolerated dose (MTD) or less, which was determined by testing increasing doses up to 320 mg QD
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Timepoint [2]
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Month 9
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Secondary outcome [1]
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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
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Assessment method [1]
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Timepoint [1]
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Week 1 Day 1 pre-dose, 0.5, 1, 2, 3, 4, and 8 hours
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Secondary outcome [2]
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Part 1 and Part 2: Area Under the Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Zanubrutinib
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Assessment method [2]
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0
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Timepoint [2]
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Week 1 Day 1 pre-dose, 0.5, 1, 2, 3, 4, and 8 hours
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Secondary outcome [3]
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Part 1 and Part 2: Maximum Observed Plasma Concentration (Cmax) After Administration of Zanubrutinib
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Assessment method [3]
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Timepoint [3]
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Week 1 Day 1 pre-dose, 0.5, 1, 2, 3, 4, and 8 hours
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Secondary outcome [4]
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Part 1 and Part 2: Maximum Observed Plasma Concentration (Cmax) After Administration of Zanubrutinib
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Assessment method [4]
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Timepoint [4]
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Week 2 Day 1 pre-dose and 24 hours
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Secondary outcome [5]
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Part 1 and Part 2: Time to Maximum Observed Plasma Concentration (Tmax) of Zanubrutinib
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Assessment method [5]
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Timepoint [5]
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Week 1 Day 1 pre-dose, 0.5, 1, 2, 3, 4, and 8 hours
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Secondary outcome [6]
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Part 1 and Part 2: Time to Maximum Observed Plasma Concentration (Tmax) of Zanubrutinib
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Assessment method [6]
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Timepoint [6]
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Week 2 Day 1 pre-dose and 24 hours
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Secondary outcome [7]
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Part 1 and Part 2: Apparent Terminal Half-life (t1/2) of Zanubrutinib
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Assessment method [7]
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Timepoint [7]
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Week 1 Day 1 pre-dose, 0.5, 1, 2, 3, 4, and 8 hours
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Secondary outcome [8]
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Part 1 and Part 2: Apparent Clearance (CL/F) of Zanubrutinib
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Assessment method [8]
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Timepoint [8]
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Week 1 Day 1 pre-dose, 0.5, 1, 2, 3, 4, and 8 hours
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Secondary outcome [9]
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Part 1 and Part 2: Apparent Volume of Distribution of Zanubrutinib During the Terminal Phase (Vz/F)
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Assessment method [9]
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0
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Timepoint [9]
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Week 1 Day 1 pre-dose, 0.5, 1, 2, 3, 4, and 8 hours
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Secondary outcome [10]
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Part 1 and Part 2: Overall Response Rate (ORR)
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Assessment method [10]
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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).
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Timepoint [10]
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Up to 6 years and 7 months
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Secondary outcome [11]
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Part 1 and Part 2: Complete Response Rate (CRR)
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Assessment method [11]
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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).
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Timepoint [11]
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Up to 6 years and 7 months
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Secondary outcome [12]
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Part 1 and Part 2: Partial Response (PR) or Better
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Assessment method [12]
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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).
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Timepoint [12]
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Up to 6 years and 7 months
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Secondary outcome [13]
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Part 1 and Part 2: Progression-free Survival (PFS)
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Assessment method [13]
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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).
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Timepoint [13]
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Up to 6 years and 7 months
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Secondary outcome [14]
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Part 1 and Part 2: Overall Survival (OS)
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Assessment method [14]
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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).
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Timepoint [14]
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Up to 6 years and 7 months
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Secondary outcome [15]
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Part 1 and Part 2: Duration of Response (DOR)
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Assessment method [15]
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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).
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Timepoint [15]
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Up to 6 years and 7 months
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Secondary outcome [16]
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Number of Participants With Greater Than 75% Bruton's Tyrosine Kinase (BTK) Occupancy
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Assessment method [16]
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Number of participants with greater than 75% BTK occupancy of zanubrutinib in peripheral blood mononuclear cells (PBMCs)
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Timepoint [16]
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Week 1 Day 1 (W1D1) predose, W1D1 4 hours, W1D2 24 hours, W1D3 predose, and W2D1 predose
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Eligibility
Key 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.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key 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.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
N/A
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Phase 1/Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
4/09/2014
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
31/03/2021
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Sample size
Target
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Accrual to date
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Final
385
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Recruitment in Australia
Recruitment state(s)
NSW,QLD,TAS,VIC,WA
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Recruitment hospital [1]
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Concord Repatriation General Hospital - Concord
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Recruitment hospital [2]
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St George Hospital - Sydney
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Recruitment hospital [3]
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Westmead Hospital - Westmead
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Recruitment hospital [4]
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Princess Alexandra Hospital - Brisbane
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Recruitment hospital [5]
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Royal Hobart Hospital - Hobart
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Recruitment hospital [6]
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Monash Health - Clayton
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Recruitment hospital [7]
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Austin Health - Heidelberg
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Recruitment hospital [8]
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St Vincent's Hospital - Melbourne
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Recruitment hospital [9]
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Peter MacCallum Cancer Centre, East Melbourne - Parkville
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Recruitment hospital [10]
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Melbourne Health - Parkville
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Recruitment hospital [11]
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Sir Charles Gairdner Hospital - Nedlands
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Recruitment postcode(s) [1]
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- Concord
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Recruitment postcode(s) [2]
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- Sydney
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Recruitment postcode(s) [3]
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- Westmead
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Recruitment postcode(s) [4]
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- Brisbane
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Recruitment postcode(s) [5]
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- Hobart
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Recruitment postcode(s) [6]
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- Clayton
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Recruitment postcode(s) [7]
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- Heidelberg
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Recruitment postcode(s) [8]
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- Melbourne
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Recruitment postcode(s) [9]
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3050 - Parkville
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Recruitment postcode(s) [10]
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- Parkville
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Recruitment postcode(s) [11]
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- Nedlands
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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Arizona
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Country [2]
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United States of America
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State/province [2]
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Michigan
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Country [3]
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United States of America
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State/province [3]
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Minnesota
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Country [4]
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United States of America
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State/province [4]
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Texas
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Country [5]
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Italy
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State/province [5]
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Bologna
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Country [6]
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Italy
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State/province [6]
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Milano
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Country [7]
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Korea, Republic of
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State/province [7]
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Busan
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Country [8]
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Korea, Republic of
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State/province [8]
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Goyang-si
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Country [9]
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Korea, Republic of
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State/province [9]
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Seoul
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Country [10]
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New Zealand
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State/province [10]
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Auckland
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Country [11]
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United Kingdom
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State/province [11]
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Devon
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
BeiGene
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
This study evaluated the safety, tolerability, pharmacokinetic profile and efficacy of
BGB-3111 in participants with B-cell lymphoid malignancies.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT02343120
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Trial related presentations / publications
Tam CS, Trotman J, Opat S, Burger JA, Cull G, Gottlieb D, Harrup R, Johnston PB, Marlton P, Munoz J, Seymour JF, Simpson D, Tedeschi A, Elstrom R, Yu Y, Tang Z, Han L, Huang J, Novotny W, Wang L, Roberts AW. Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. Blood. 2019 Sep 12;134(11):851-859. doi: 10.1182/blood.2019001160. Epub 2019 Jul 24.
Trotman J, Opat S, Gottlieb D, Simpson D, Marlton P, Cull G, Munoz J, Tedeschi A, Roberts AW, Seymour JF, Atwal SK, Yu Y, Novotny W, Holmgren E, Tan Z, Hilger JD, Huang J, Tam CS. Zanubrutinib for the treatment of patients with Waldenstrom macroglobulinemia: 3 years of follow-up. Blood. 2020 Oct 29;136(18):2027-2037. doi: 10.1182/blood.2020006449. Erratum In: Blood. 2021 Feb 25;137(8):1131.
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
Cull G, Burger JA, Opat S, Gottlieb D, Verner E, Trotman J, Marlton P, Munoz J, Johnston P, Simpson D, Stern JC, Prathikanti R, Wu K, Novotny W, Huang J, Tam CS. Zanubrutinib for treatment-naive and relapsed/refractory chronic lymphocytic leukaemia: long-term follow-up of the phase I/II AU-003 study. Br J Haematol. 2022 Mar;196(5):1209-1218. doi: 10.1111/bjh.17994. Epub 2021 Dec 16.
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Public notes
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Contacts
Principal investigator
Name
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Study Director
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Address
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BeiGene
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Fax
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT02343120
Download to PDF