TriangleNCT02343120 · CITED IN SOURCE DOCUMENTS
Study of the Safety and Pharmacokinetics of BGB-3111 in Subjects With B-Cell Lymphoid Malignancies
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE1, PHASE2
- Status at capture
- COMPLETED
- Registry last update
- 2022-04-28
This study evaluated the safety, tolerability, pharmacokinetic profile and efficacy of BGB-3111 in participants with B-cell lymphoid malignancies.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Part 1 and Part 2: Number of Participants With Adverse Events
Part 1: Recommended Phase 2 Dose (RP2D) for Zanubrutinib
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
Part 1 and Part 2: Area Under the Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Zanubrutinib
Part 1 and Part 2: Maximum Observed Plasma Concentration (Cmax) After Administration of Zanubrutinib
Part 1 and Part 2: Maximum Observed Plasma Concentration (Cmax) After Administration of Zanubrutinib
Part 1 and Part 2: Time to Maximum Observed Plasma Concentration (Tmax) of Zanubrutinib
Part 1 and Part 2: Time to Maximum Observed Plasma Concentration (Tmax) of Zanubrutinib
Part 1 and Part 2: Apparent Terminal Half-life (t1/2) of Zanubrutinib
Part 1 and Part 2: Apparent Clearance (CL/F) of Zanubrutinib
Part 1 and Part 2: Apparent Volume of Distribution of Zanubrutinib During the Terminal Phase (Vz/F)
Part 1 and Part 2: Overall Response Rate (ORR)
Part 1 and Part 2: Complete Response Rate (CRR)
Part 1 and Part 2: Partial Response (PR) or Better
Part 1 and Part 2: Progression-free Survival (PFS)
Part 1 and Part 2: Overall Survival (OS)
Part 1 and Part 2: Duration of Response (DOR)
Number of Participants With Greater Than 75% Bruton's Tyrosine Kinase (BTK) Occupancy
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility 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.
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- 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
- intervention Names
- Drug: Zanubrutinib
- label
- Zanubrutinib
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Zanubrutinib
- description
- Oral administration by capsule
- name
- Zanubrutinib
- other Names
- BGB-3111
- Brukinsa
- type
- DRUG
Study design
- allocation
- NA
- intervention Model
- SINGLE_GROUP
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 385
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- Number of participants with adverse events and serious adverse events, including clinically relevant physical examinations and laboratory measurements
- measure
- Part 1 and Part 2: Number of Participants With Adverse Events
- time Frame
- Up to approximately 6 years and 7 months
- description
- RP2D for zanubrutinib was the maximum tolerated dose (MTD) or less, which was determined by testing increasing doses up to 320 mg QD
- measure
- Part 1: Recommended Phase 2 Dose (RP2D) for Zanubrutinib
- time Frame
- Month 9
- secondary Outcomes
- measure
- 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
- measure
- 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
- measure
- 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
- measure
- 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
- measure
- 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
- measure
- 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
- measure
- 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
- measure
- 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
- measure
- 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
- description
- 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).
- measure
- Part 1 and Part 2: Overall Response Rate (ORR)
- time Frame
- Up to 6 years and 7 months
- description
- 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).
- measure
- Part 1 and Part 2: Complete Response Rate (CRR)
- time Frame
- Up to 6 years and 7 months
- description
- 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).
- measure
- Part 1 and Part 2: Partial Response (PR) or Better
- time Frame
- Up to 6 years and 7 months
Full study description
- brief Summary
- This study evaluated the safety, tolerability, pharmacokinetic profile and efficacy of BGB-3111 in participants with B-cell lymphoid malignancies.
Source references
- references
- citation
- 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.
- pmid
- 31340982
- type
- BACKGROUND
- citation
- 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.
- pmid
- 32698195
- type
- BACKGROUND
- citation
- 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
- type
- BACKGROUND
- citation
- 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.
- pmid
- 34915592
- type
- BACKGROUND
- citation
- Alfaifi A, Bahashwan S, Alsaadi M, Ageel AH, Ahmed HH, Fatima K, Malhan H, Qadri I, Almehdar H. Advancements in B-Cell Non-Hodgkin's Lymphoma: From Signaling Pathways to Targeted Therapies. Adv Hematol. 2024 Nov 12;2024:5948170. doi: 10.1155/2024/5948170. eCollection 2024.
- pmid
- 39563886
- type
- DERIVED
- citation
- Liu Y, Ma X, Wu X, Hou X, Jin W, Fu L, Xun X, Yu Y, Shen Z. Zanubrutinib is effective in non-germinal-center B-cell-like diffuse large B-cell lymphoma with mutated CD79B, high TCL1A expression, or over- expressed MYC/BCL-2. Leuk Lymphoma. 2024 Aug;65(8):1079-1089. doi: 10.1080/10428194.2024.2343779. Epub 2024 May 22.
- pmid
- 38775302
- type
- DERIVED
- citation
- Moslehi JJ, Furman RR, Tam CS, Salem JE, Flowers CR, Cohen A, Zhang M, Zhang J, Chen L, Ma H, Brown JR. Cardiovascular events reported in patients with B-cell malignancies treated with zanubrutinib. Blood Adv. 2024 May 28;8(10):2478-2490. doi: 10.1182/bloodadvances.2023011641.
- pmid
- 38502198
- type
- DERIVED
- citation
- Xu W, Yang S, Tam CS, Seymour JF, Zhou K, Opat S, Qiu L, Sun M, Wang T, Trotman J, Pan L, Gao S, Zhou J, Zhou D, Zhu J, Song Y, Hu J, Feng R, Huang H, Su D, Shi M, Li J. Zanubrutinib Monotherapy for Naive and Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Pooled Analysis of Three Studies. Adv Ther. 2022 Sep;39(9):4250-4265. doi: 10.1007/s12325-022-02238-7. Epub 2022 Jul 28.
- pmid
- 35900694
- type
- DERIVED
- citation
- Phillips T, Chan H, Tam CS, Tedeschi A, Johnston P, Oh SY, Opat S, Eom HS, Allewelt H, Stern JC, Tan Z, Novotny W, Huang J, Trotman J. Zanubrutinib monotherapy in relapsed/refractory indolent non-Hodgkin lymphoma. Blood Adv. 2022 Jun 14;6(11):3472-3479. doi: 10.1182/bloodadvances.2021006083.
- pmid
- 35390135
- type
- DERIVED
- citation
- Tam CS, Opat S, Simpson D, Cull G, Munoz J, Phillips TJ, Kim WS, Rule S, Atwal SK, Wei R, Novotny W, Huang J, Wang M, Trotman J. Zanubrutinib for the treatment of relapsed or refractory mantle cell lymphoma. Blood Adv. 2021 Jun 22;5(12):2577-2585. doi: 10.1182/bloodadvances.2020004074.
- pmid
- 34152395
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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- nt in 14% of patients. The MIPI score was low in 58%, intermediate in 29%, and high risk in 13%. The efficacy of BRUKINSA was also assessed in BGB-3111-AU-003 [NCT02343120], a Phase 1/2, open-label, dose-escalation, global, multicenter, single-arm trial of B cell malignancies including 32 previously treated MCL patients treated w
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- therapy; 88% had prior rituximab-based chemotherapy; 32% had refractory disease at study entry. The efficacy of BRUKINSA was also assessed in BGB-3111-AU-003 [NCT02343120], an open-label, multicenter, single-arm trial that included 20 patients with previously treated MZL (45% having extranodal MZL, 25% nodal, 30% splenic). BRUKI
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- s evaluated in 118 patients with MCL who received at least one prior therapy in two single-arm clinical trials, BGB-3111-206 [NCT03206970] and BGB-3111-AU-003 [NCT02343120] [see Clinical Studies (14.1) ] . The median age of patients who received BRUKINSA in studies BGB-3111-206 and BGB-3111-AU-003 was 62 years (range: 34 to 86),
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Preserved source evidence · Not medical advice