Study of the Safety and Pharmacokinetics of BGB-3111 in Subjects With B-Cell Lymphoid Malignancies

NCT ID: NCT02343120

Last Updated: 2022-04-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 385 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-04
• Study Completion Date: 2021-03-31

Brief Summary

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

Conditions

B-cell Malignancies

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Zanubrutinib

Intervention Type: DRUG

Oral administration by capsule

Interventions

Zanubrutinib

Oral administration by capsule

Intervention Type: DRUG

Other Intervention Names

BGB-3111; Brukinsa

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BeiGene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

BeiGene

Locations

Banner MD Anderson Cancer Centre

Gilbert, Arizona, United States

University of Michigan

Ann Arbor, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

M.D. Anderson Cancer Center

Houston, Texas, United States

Concord Repatriation General Hospital

Concord, New South Wales, Australia

St George Hospital

Sydney, New South Wales, Australia

Westmead Hospital

Westmead, New South Wales, Australia

Princess Alexandra Hospital

Brisbane, Queensland, Australia

Royal Hobart Hospital

Hobart, Tasmania, Australia

Monash Health

Clayton, Victoria, Australia

Austin Health

Heidelberg, Victoria, Australia

St Vincent's Hospital

Melbourne, Victoria, Australia

Peter MacCallum Cancer Centre, East Melbourne

Parkville, Victoria, Australia

Melbourne Health

Parkville, Victoria, Australia

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

Policlinico S.Orsola Malpighi, AOU di Bologna

Bologna, , Italy

Ospedale Maggiore Policlinico, Fondazione IRCCS Ca' Granda

Milan, , Italy

North Shore Hospital

Auckland, , New Zealand

Dong-A University Medical Centre

Busan, , South Korea

Inje University Busan Paik Hospital

Busan, , South Korea

National Cancer Center

Goyang-si, , South Korea

Samsung Medical Center

Seoul, , South Korea

Derriford Hospital

Plymouth, Devon, United Kingdom

Countries

United States; Australia; Italy; New Zealand; South Korea; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 31340982 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 32698195 (View on PubMed)

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

Reference Type: BACKGROUND

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.

Reference Type: BACKGROUND

PMID: 34915592 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 39563886 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 38502198 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35900694 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35390135 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34152395 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-003364-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BGB-3111-AU-003

Identifier Type: -

Identifier Source: org_study_id