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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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
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
Secondary ID [1] 0 0
2016-003364-39
Secondary ID [2] 0 0
BGB-3111-AU-003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
B-cell Malignancies 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1 and Part 2: Number of Participants With Adverse Events
Timepoint [1] 0 0
Up to approximately 6 years and 7 months
Primary outcome [2] 0 0
Part 1: Recommended Phase 2 Dose (RP2D) for Zanubrutinib
Timepoint [2] 0 0
Month 9
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
Week 1 Day 1 pre-dose, 0.5, 1, 2, 3, 4, and 8 hours
Secondary outcome [2] 0 0
Part 1 and Part 2: Area Under the Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Zanubrutinib
Timepoint [2] 0 0
Week 1 Day 1 pre-dose, 0.5, 1, 2, 3, 4, and 8 hours
Secondary outcome [3] 0 0
Part 1 and Part 2: Maximum Observed Plasma Concentration (Cmax) After Administration of Zanubrutinib
Timepoint [3] 0 0
Week 1 Day 1 pre-dose, 0.5, 1, 2, 3, 4, and 8 hours
Secondary outcome [4] 0 0
Part 1 and Part 2: Maximum Observed Plasma Concentration (Cmax) After Administration of Zanubrutinib
Timepoint [4] 0 0
Week 2 Day 1 pre-dose and 24 hours
Secondary outcome [5] 0 0
Part 1 and Part 2: Time to Maximum Observed Plasma Concentration (Tmax) of Zanubrutinib
Timepoint [5] 0 0
Week 1 Day 1 pre-dose, 0.5, 1, 2, 3, 4, and 8 hours
Secondary outcome [6] 0 0
Part 1 and Part 2: Time to Maximum Observed Plasma Concentration (Tmax) of Zanubrutinib
Timepoint [6] 0 0
Week 2 Day 1 pre-dose and 24 hours
Secondary outcome [7] 0 0
Part 1 and Part 2: Apparent Terminal Half-life (t1/2) of Zanubrutinib
Timepoint [7] 0 0
Week 1 Day 1 pre-dose, 0.5, 1, 2, 3, 4, and 8 hours
Secondary outcome [8] 0 0
Part 1 and Part 2: Apparent Clearance (CL/F) of Zanubrutinib
Timepoint [8] 0 0
Week 1 Day 1 pre-dose, 0.5, 1, 2, 3, 4, and 8 hours
Secondary outcome [9] 0 0
Part 1 and Part 2: Apparent Volume of Distribution of Zanubrutinib During the Terminal Phase (Vz/F)
Timepoint [9] 0 0
Week 1 Day 1 pre-dose, 0.5, 1, 2, 3, 4, and 8 hours
Secondary outcome [10] 0 0
Part 1 and Part 2: Overall Response Rate (ORR)
Timepoint [10] 0 0
Up to 6 years and 7 months
Secondary outcome [11] 0 0
Part 1 and Part 2: Complete Response Rate (CRR)
Timepoint [11] 0 0
Up to 6 years and 7 months
Secondary outcome [12] 0 0
Part 1 and Part 2: Partial Response (PR) or Better
Timepoint [12] 0 0
Up to 6 years and 7 months
Secondary outcome [13] 0 0
Part 1 and Part 2: Progression-free Survival (PFS)
Timepoint [13] 0 0
Up to 6 years and 7 months
Secondary outcome [14] 0 0
Part 1 and Part 2: Overall Survival (OS)
Timepoint [14] 0 0
Up to 6 years and 7 months
Secondary outcome [15] 0 0
Part 1 and Part 2: Duration of Response (DOR)
Timepoint [15] 0 0
Up to 6 years and 7 months
Secondary outcome [16] 0 0
Number of Participants With Greater Than 75% Bruton's Tyrosine Kinase (BTK) Occupancy
Timepoint [16] 0 0
Week 1 Day 1 (W1D1) predose, W1D1 4 hours, W1D2 24 hours, W1D3 predose, and W2D1 predose

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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
4/09/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
31/03/2021
Sample size
Target
Accrual to date
Final
385
Recruitment in Australia
Recruitment state(s)
NSW,QLD,TAS,VIC,WA
Recruitment hospital [1] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [2] 0 0
St George Hospital - Sydney
Recruitment hospital [3] 0 0
Westmead Hospital - Westmead
Recruitment hospital [4] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment hospital [5] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [6] 0 0
Monash Health - Clayton
Recruitment hospital [7] 0 0
Austin Health - Heidelberg
Recruitment hospital [8] 0 0
St Vincent's Hospital - Melbourne
Recruitment hospital [9] 0 0
Peter MacCallum Cancer Centre, East Melbourne - Parkville
Recruitment hospital [10] 0 0
Melbourne Health - Parkville
Recruitment hospital [11] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
- Concord
Recruitment postcode(s) [2] 0 0
- Sydney
Recruitment postcode(s) [3] 0 0
- Westmead
Recruitment postcode(s) [4] 0 0
- Brisbane
Recruitment postcode(s) [5] 0 0
- Hobart
Recruitment postcode(s) [6] 0 0
- Clayton
Recruitment postcode(s) [7] 0 0
- Heidelberg
Recruitment postcode(s) [8] 0 0
- Melbourne
Recruitment postcode(s) [9] 0 0
3050 - Parkville
Recruitment postcode(s) [10] 0 0
- Parkville
Recruitment postcode(s) [11] 0 0
- Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Michigan
Country [3] 0 0
United States of America
State/province [3] 0 0
Minnesota
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
Italy
State/province [5] 0 0
Bologna
Country [6] 0 0
Italy
State/province [6] 0 0
Milano
Country [7] 0 0
Korea, Republic of
State/province [7] 0 0
Busan
Country [8] 0 0
Korea, Republic of
State/province [8] 0 0
Goyang-si
Country [9] 0 0
Korea, Republic of
State/province [9] 0 0
Seoul
Country [10] 0 0
New Zealand
State/province [10] 0 0
Auckland
Country [11] 0 0
United Kingdom
State/province [11] 0 0
Devon

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
BeiGene
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
BeiGene
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT02343120