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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02569476




Registration number
NCT02569476
Ethics application status
Date submitted
18/09/2015
Date registered
6/10/2015

Titles & IDs
Public title
BGB 3111 in Combination With Obinutuzumab in Participants With B-Cell Lymphoid Malignancies
Scientific title
A Phase 1b Study to Assess Safety, Tolerability and Antitumor Activity of the Combination of BGB 3111 With Obinutuzumab in Subjects With B-Cell Lymphoid Malignancies
Secondary ID [1] 0 0
BGB-3111_GA101_Study_001
Universal Trial Number (UTN)
Trial acronym
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: Zanubrutinib and Obinutuzumab - In the dose-escalation part, dose levels and regimens were evaluated. In the indication-specific expansion cohorts, participants were assigned to different cohorts based on histology type.
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1 : Number Of Participants Experiencing Adverse Events
Assessment method [1] 0 0
An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product (zanubrutinib in combination with obinutuzumab). An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of the study drug. A serious AE (SAE) was any untoward medical occurrence that, at any dose. * resulted in death, * was life threatening, * required hospitalization or prolongation of existing hospitalization, * resulted in disability/incapacity, * was a congenital anomaly/birth defect.
Timepoint [1] 0 0
Day 1 (first dose) through 4 years and 8 months
Primary outcome [2] 0 0
Part 1: Number Of Participants With Clinical Laboratory Abnormalities
Assessment method [2] 0 0
Laboratory results are reported as participants with shifts towards (high directionality) or away (low directionality) from Grade 3 or Higher Toxicity.
Timepoint [2] 0 0
Day -28 to -1 (predose) through 4 years and 8 months
Primary outcome [3] 0 0
Part 1: Number Of Deaths
Assessment method [3] 0 0
An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product (zanubrutinib in combination with obinutuzumab). An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. An SAE was any untoward medical occurrence that, at any dose: * resulted in death, * was life threatening, * required hospitalization or prolongation of existing hospitalization, * resulted in disability/incapacity, * was a congenital anomaly/birth defect.
Timepoint [3] 0 0
Day 1 (first dose) through 4 years and 8 months
Primary outcome [4] 0 0
Part 1: Number Of Participants Experiencing Dose-limiting Toxicity (DLT)
Assessment method [4] 0 0
Dose-limiting toxicities were defined as a toxicity or AE occurring during the DLT assessment period (first 29 days of treatment), which is not clearly attributable to a cause other than zanubrutinib and/or obinutuzumab (such as disease progression, underlying illness, concurrent illness or concomitant medication) and meets one of the following criteria: * Grade 3 or 4 drug-related non-hematologic toxicity (excluding Grade 3 nausea, vomiting, hypertension, and asymptomatic laboratory abnormalities), * Grade 4 drug-related hematologic toxicity persisting for \>14 days, * any grade toxicity, which in the judgment of the investigator or Sponsor, required removal of the participant from the study.
Timepoint [4] 0 0
Day 1 (first dose) through 4 years and 8 months
Primary outcome [5] 0 0
Part 1 and Part 2: Number Of Participants Achieving A Best Response Of Partial Response
Assessment method [5] 0 0
Partial response was defined as follows: * = 50% reduction of serum IgM from baseline, * reduction in lymphadenopathy/splenomegaly (if present at baseline). For response assessments that occurred during cycles where a CT scan was not required, then results from prior scans (up to 12 weeks during the first 48 weeks and up to 24 weeks thereafter) could be carried forward in those participants with extramedullary disease at baseline.
Timepoint [5] 0 0
Day 1 (first dose) through 4 years and 8 months
Secondary outcome [1] 0 0
Part 1 and Part 2: Number Of Participants Achieving A Best Response Of Complete Response
Assessment method [1] 0 0
Complete response was defined as follows: * normal serum IgM values, * disappearance of monoclonal protein by immunofixation, * no histological evidence of bone marrow involvement, * complete resolution of lymphadenopathy/splenomegaly (if present at baseline) For response assessments that occurred during cycles where a computed tomography (CT) scan was not required, then results from prior scans (up to 12 weeks during the first 48 weeks and up to 24 weeks thereafter) could be carried forward in those participants with extramedullary disease at baseline.
Timepoint [1] 0 0
Day 1 (first dose) through 4 years and 8 months
Secondary outcome [2] 0 0
Part 1 and Part 2: Progression-free Survival (PFS)
Assessment method [2] 0 0
Progression-free survival was defined as time (in months) from the start of treatment with zanubrutinib or obinutuzumab to the first documented disease progression or death due to any cause, whichever occurred first. Results are reported as the median months for each of the B-cell malignancy subtypes: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), Waldenström macroglobulinemia (WM), follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), and non-germinal center B-cell-like (GCB) diffuse large B-cell lymphoma (DLBCL).
Timepoint [2] 0 0
Day 1 (first dose) through 4 years and 8 months
Secondary outcome [3] 0 0
Part 1 and Part 2: Duration Of Response (DOR)
Assessment method [3] 0 0
Duration of response for responders was defined as the time (in months) from the date of the earliest qualifying response to the date of progressive disease or death due to any cause (whichever occurred earlier). Duration of response was analyzed using the same methods as the analysis for PFS. Responses after initiating new anticancer therapy, roll over to the long-term extension (LTE) study, or the first occurrence of disease progression were not considered in the analysis.
Timepoint [3] 0 0
Day 1 (first dose) through 4 years and 8 months
Secondary outcome [4] 0 0
Part 1 and Part 2: Time To Response (TTR)
Assessment method [4] 0 0
The TTR for responders was defined as time (in months) from the start of the study treatment to the date of the earliest qualifying response. The TTR was summarized using descriptive statistics. Responses after initiating new anticancer therapy, roll over to the LTE study, or the first occurrence of disease progression were not considered in the analysis of TTR.
Timepoint [4] 0 0
Day 1 (first dose) through 4 years and 8 months
Secondary outcome [5] 0 0
Part 1 and Part 2: Overall Survival (OS)
Assessment method [5] 0 0
Overall survival was defined as the time (in months) from the date of the start of the study treatment to death due to any cause. Participants who were alive before final database lock or discontinuation of the study (discontinued study due to reasons other than death) were censored at their last known alive date on or before database lock.
Timepoint [5] 0 0
Day 1 (first dose) through 4 years and 8 months
Secondary outcome [6] 0 0
Part 1 and Part 2: Hematologic Improvement In Participants With CLL
Assessment method [6] 0 0
The number and percentage of participants with CLL with anemia (hemoglobin =110 grams/liter \[g/L\]), neutropenia (absolute neutrophil count =1.5 x 10\^9/L), or thrombocytopenia (platelet count =100 x 10\^9/L) at baseline were estimated.
Timepoint [6] 0 0
Day 1 (first dose) through 4 years and 8 months
Secondary outcome [7] 0 0
Part 1: Area Under The Plasma Concentration-time Curve From Time 0 To The Time Of The Last Measurable Concentration (AUClast) Of Zanubrutinib
Assessment method [7] 0 0
Timepoint [7] 0 0
Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7
Secondary outcome [8] 0 0
Part 1: Area Under The Plasma Concentration-time Curve From Time 0 To Infinity Time (AUC) Of Zanubrutinib
Assessment method [8] 0 0
Timepoint [8] 0 0
Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7
Secondary outcome [9] 0 0
Part 1: Maximum Plasma Concentration (Cmax) Of Zanubrutinib
Assessment method [9] 0 0
Timepoint [9] 0 0
Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7
Secondary outcome [10] 0 0
Part 1: Time To Maximum Plasma Concentration (Tmax) Of Zanubrutinib
Assessment method [10] 0 0
Timepoint [10] 0 0
Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7
Secondary outcome [11] 0 0
Part 1: Terminal Elimination Half-life (t1/2) Of Zanubrutinib
Assessment method [11] 0 0
Timepoint [11] 0 0
Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7
Secondary outcome [12] 0 0
Part 1: Apparent Clearance (CL/F) Of Zanubrutinib
Assessment method [12] 0 0
Timepoint [12] 0 0
Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7
Secondary outcome [13] 0 0
Part 1: Apparent Volume Of Distribution (Vz/F) Of Zanubrutinib
Assessment method [13] 0 0
Timepoint [13] 0 0
Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7
Secondary outcome [14] 0 0
Part 1 and Part 2: Steady State AUClast Of Zanubrutinib
Assessment method [14] 0 0
Timepoint [14] 0 0
Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7
Secondary outcome [15] 0 0
Part 1 and Part 2: Steady State Cmax of Zanubrutinib
Assessment method [15] 0 0
Timepoint [15] 0 0
Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7
Secondary outcome [16] 0 0
Part 1 and Part 2: Steady State Tmax Of Zanubrutinib
Assessment method [16] 0 0
Timepoint [16] 0 0
Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7
Secondary outcome [17] 0 0
Part 2: Number Of Participants Experiencing Adverse Events
Assessment method [17] 0 0
An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product (zanubrutinib in combination with obinutuzumab). An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. An SAE was any untoward medical occurrence that, at any dose,: * resulted in death, * was life threatening, * required hospitalization or prolongation of existing hospitalization, * resulted in disability/incapacity, * was a congenital anomaly/birth defect.
Timepoint [17] 0 0
Day 1 (first dose) through 4 years and 8 months
Secondary outcome [18] 0 0
Part 2: Number Of Participants With Clinical Laboratory Abnormalities
Assessment method [18] 0 0
Results are reported as participants with shifts towards (high directionality) or away (low directionality) from Grade 3 or Higher Toxicity.
Timepoint [18] 0 0
Day -28 to -1 (predose) through 4 years and 8 months
Secondary outcome [19] 0 0
Part 2: Number Of Deaths
Assessment method [19] 0 0
An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product (zanubrutinib in combination with obinutuzumab). An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. An SAE was any untoward medical occurrence that, at any dose,: * resulted in death, * is life threatening, * required hospitalization or prolongation of existing hospitalization, * resulted in disability/incapacity, * was a congenital anomaly/birth defect.
Timepoint [19] 0 0
Day 1 (first dose) through 4 years and 8 months

Eligibility
Key inclusion criteria
* Aged =18 years, able and willing to provide written informed consent and to comply with the study protocol.
* Laboratory parameters as specified below:

* Hematologic: Platelet count >40x10^9/liter (L) (may be post-transfusion); absolute neutrophil count >1.0x10^9/L (growth factor use is allowed to bring pre-treatment neutrophils to >1.0x10^9 cells/L if marrow infiltration is involved).
* Hepatic: Total bilirubin <3 x upper limit normal (ULN); and aspartate aminotransferase and alanine transaminase =3 x ULN.
* Renal: Creatinine clearance =50 milliliters/minute (as estimated by the Cockcroft Gault equation or as measured by nuclear medicine scan or 24-hour urine collection); participants requiring hemodialysis will be excluded.
* Anticipated survival of at least 6 months.
* Eastern Cooperative Oncology Group performance status of 0 to 2.
* Female participants of childbearing potential and non-sterile males must have agreed to practice at least one of the following methods of birth control with partner(s) throughout the study and for =3 months after discontinuing zanubrutinib or =18 months following obinutuzumab treatment, whichever was longer: total abstinence from sexual intercourse, double barrier contraception, intra uterine device or hormonal contraceptive initiated at least 3 months prior to first administration of study drug.
* Male participants must have not donated sperm from first study drug administration, until 3 months after zanubrutinib discontinuation or 18 months following obinutuzumab treatment, whichever is longer.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Known central nervous system lymphoma or leukemia.
* Known prolymphocytic leukemia or history of, or currently suspected, Richter's syndrome.
* Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.
* History of significant cardiovascular disease.
* Severe or debilitating pulmonary disease.
* History of severe allergic or anaphylactic reactions to monoclonal antibody therapy.
* Prior Bruton tyrosine kinase inhibitor treatment.
* Used medications which were strong cytochrome P450 (CYP) 3A inhibitors and strong CYP3A inducers.
* Vaccination with a live vaccine within 28 days of the initiation of treatment.
* Allogeneic stem cell transplantation within 6 months, or had active graft versus host disease requiring ongoing immunosuppression.
* Receipt of the following treatment prior to first administration of zanubrutinib, corticosteroids given with anti-neoplastic intent within 7 days, chemotherapy or radiotherapy within 3 weeks, monoclonal antibody within 4 weeks.
* Participated in any investigational drug study within 28 days of study entry, or not recovered from non-hematologic toxicity of any prior chemotherapy up to = Grade 1 (except for alopecia).
* History of other active malignancies within 2 years of study entry.
* Major surgery in the past 4 weeks.
* Active symptomatic fungal, bacterial and/or viral infection including evidence of infection with human immunodeficiency virus, human T cell lymphotropic virus seropositive status.
* Inability to comply with the study procedures.
* Pregnant or nursing women.
* Any illness or condition that in the opinion of the investigator may have affected the safety of treatment or evaluation of any study's endpoints.

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
13/01/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
2/09/2020
Sample size
Target
Accrual to date
Final
119
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
St George Hospital - Kogarah
Recruitment hospital [2] 0 0
Brisbane Clinic For Lymphoma - Greenslopes
Recruitment hospital [3] 0 0
Ashford Cancer Centre Research Northeast - Windsor Gardens
Recruitment hospital [4] 0 0
St Vincents Hospital Melbourne - Fitzroy
Recruitment hospital [5] 0 0
Barwon Health the Geelong Hospital - Geelong
Recruitment hospital [6] 0 0
St Frances Xavier Cabrini Hospital - Malvern
Recruitment hospital [7] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [8] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
4120 - Greenslopes
Recruitment postcode(s) [3] 0 0
5087 - Windsor Gardens
Recruitment postcode(s) [4] 0 0
3065 - Fitzroy
Recruitment postcode(s) [5] 0 0
3220 - Geelong
Recruitment postcode(s) [6] 0 0
3144 - Malvern
Recruitment postcode(s) [7] 0 0
3004 - Melbourne
Recruitment postcode(s) [8] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Tennessee
Country [3] 0 0
Korea, Republic of
State/province [3] 0 0
Seoul Teugbyeolsi

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
BeiGene
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
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

TypeOther DetailsAttachment
Study protocol
Statistical analysis plan



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02569476