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BTK Inhibitor BGB-3111 in Chinese Participants With Large B-Cell Lymphoma (Non-GCB) and Indolent Lymphoma (FL and MZL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03520920
Recruitment Status : Completed
First Posted : May 11, 2018
Last Update Posted : September 30, 2020
Sponsor:
Information provided by (Responsible Party):
BeiGene

Brief Summary:
This is a multicenter open-label phase 2 study to evaluate efficacy, safety and tolerability of BGB-3111 160 mg twice daily in combination with rituximab in Chinese participants with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (non-GCB Subtype) and Relapsed/Refractory Indolent Lymphoma (Follicular Lymphoma (FL) and Marginal Zone Lymphoma (MZL)).

Condition or disease Intervention/treatment Phase
Marginal Zone Lymphoma Follicular Lymphoma Diffuse Large B-Cell Lymphoma Drug: Zanubrutinib Drug: Rituximab Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 41 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study to Assess the Safety, Tolerability, and Activity of BGB-3111 in Combination With Rituximab in Chinese Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma and R/R Indolent Lymphoma
Actual Study Start Date : January 4, 2018
Actual Primary Completion Date : August 28, 2020
Actual Study Completion Date : August 28, 2020


Arm Intervention/treatment
Experimental: Non-GCB DLBCL
Participants with non germinal center B-cell-like diffuse large B-cell lymphoma (non-GCB DLBCL) will receive zanubrutinib plus rituximab for up to 24 months
Drug: Zanubrutinib
160 mg orally (PO) twice daily (BID)
Other Name: BGB-3111

Drug: Rituximab
375 mg/m2 intravenously on Cycle 1 Days 1, 8, 15, 22, and on Day 1 of Cycles 4, 6, 8, 10. Each cycle is 28 days long.

Experimental: R/R FL or MZL
Participants with relapsed/refractory (R/R) FL or MZL will receive zanubrutinib plus rituximab for up to 24 months
Drug: Zanubrutinib
160 mg orally (PO) twice daily (BID)
Other Name: BGB-3111

Drug: Rituximab
375 mg/m2 intravenously on Cycle 1 Days 1, 8, 15, 22, and on Day 1 of Cycles 4, 6, 8, 10. Each cycle is 28 days long.




Primary Outcome Measures :
  1. overall response rate(ORR) [ Time Frame: up to 2 years ]
    The achievement of either a partial response (PR) or complete response (CR)


Secondary Outcome Measures :
  1. Progression free survival (PFS) [ Time Frame: up to 2 years ]
    Defined as time from first dose of BGB-3111 until first documentation of Progression (by international working group (IWG) on non-Hodgkin lymphoma (NHL) criteria) or death, whichever comes first

  2. Duration of response (DOR) [ Time Frame: up to 2 years ]
    Defined as the time from the date that the response criteria are first met to the date that progressive disease (PD) is objectively documented or death, whichever occurs first.

  3. Overall survival (OS) [ Time Frame: up to 2 years ]
    Defined as the time from first dose of BGB-3111 until death.

  4. Time to response (TTR) [ Time Frame: up to 2 years ]
    Defined as the time from first dose of BGB-3111 to documentation of a response.

  5. Rate of complete response or complete metabolic response [ Time Frame: up to 2 years ]
    Defined as the time from first dose of BGB-3111 to complete response or complete metabolic response

  6. Number of participants experiencing Adverse Events (AEs) [ Time Frame: Up to 2 years ]
  7. Number of participants experiencing Serious Adverse Events (SAEs) [ Time Frame: Up to 2 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  1. Age ≥ 18 years at time of signing of informed consent.
  2. Measurable disease by CT or positron emission tomography (PET)/CT or magnetic resonance imaging (MRI), defined as ≥ 1 nodal lesion that is > 1.5 cm in the longest diameter, or ≥ 1 extra-nodal lesion (e.g. hepatic nodules) that is > 1 cm in the longest diameter.
  3. Availability of archival or fresh tumor tissue sample from an evaluable core or excisional biopsy.
  4. participants meet the following criteria:

    1. Cohort 1: R/R non-GCB DLBCL I. Histologically confirmed non-GCB DLBCL per Hans criteria with non-transformed disease; additional methodologies for confirming non-GCB DLBCL may be considered in consultation with the medical monitor ii. Relapsed disease (disease progression after most recent therapy for DLBCL occurring more than 6 months after the completion of last therapy) or refractory disease (failure to achieve CR or PR to therapy for non-GCB DLBCL or disease progression within 6 months after completion of the most recent therapy for non-GCB DLBCL) iii. Must have received at least one standard anthracycline ± rituximab based treatment (e.g. R- CHOP) or CVP+/- R for DLBCL
    2. Cohort 2: R/R FL or R/R MZL I. Histologically confirmed CD20+ FL (Grade 1, 2, or 3a) or MZL ii. Relapsed disease (disease progression after most recent therapy for FL or MZL occurring more than 6 months after the completion of last therapy) or refractory disease (failure to achieve CR or PR to most recent therapy for FL or MZL, or disease progression within 6 months after completion of the most recent therapy for FL or MZL).
  5. Laboratory parameters as specified below:

    1. Hematologic: Platelet count ≥ 75 x 109/L independent of growth factor or transfusion within 7 days of study entry; absolute neutrophil count (ANC) ≥ 1 x 109/L independent of growth factor within 7 days of study entry, hemoglobin (Hgb) > 8 g/dL within 7 days of study entry.
    2. Hepatic: Total bilirubin ≤ 2x upper limit of normal (ULN) unless documented Gilbert's syndrome; aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and alanine transaminase (ALT)/serum glutamic-pyruvic transaminase (SGPT) ≤ 3x ULN.
    3. Renal: Creatinine clearance ≥ 30 mL/min (as estimated by the Cockcroft-Gault equation based on ideal body weight or as measured by nuclear medicine scan or 24 hour urine collection)
    4. International normalized ratio and activated partial thromboplastin time (aPTT) ≤ 1.5x ULN. participants with anti-phospholipid syndrome, acquired von Willebrand disease, factor inhibitors or on vitamin K antagonist may be enrolled after discussion with the Medical Monitor.
  6. Left ventricular ejection fraction (LVEF) ≥ 50%.
  7. Life expectancy ≥ 6 months.
  8. Eastern Cooperative Oncology Group performance status of 0, 1, or 2.
  9. Female participants of childbearing potential must practice highly effective methods of contraception initiated prior to first dose of study drug, for the duration of the study, and for ≥ 90 days after the last dose of zanubrutinib, or 12 months after the last dose of rituximab, whichever is longer.
  10. Male participants are eligible if vasectomized or if they agree to the use of barrier contraception in combination with other methods above during the study treatment period and for ≥ 90 days after the last dose of zanubrutinib.
  11. Able to provide written informed consent and can understand and comply with the requirements of the study.

Key Exclusion Criteria:

  1. Known central nervous system lymphoma or leukemia.
  2. Histological confirmed gastric mucosa-associated lymphoid tissue (MALT) type MZL
  3. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.
  4. Clinically significant cardiovascular disease.
  5. History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention
  6. History of stroke or intracranial hemorrhage within 6 months before first dose of study drug.
  7. Severe or debilitating pulmonary disease.
  8. Hypersensitivity reaction to BGB-3111 or rituximab or any of the other ingredients of the study drugs.
  9. Prior Bruton tyrosine kinase (BTK) inhibitor treatment.
  10. Requires ongoing treatment with a strong Cytochrome P450 protein (CYP3A) inhibitor or inducer.
  11. Vaccination with a live vaccine within 28 days of the first dose of study drug.
  12. Hematopoietic stem cell transplantation within 6 months of first dose of study drug.
  13. Receipt of the following treatment prior to first dose of study drug:

    1. Corticosteroids at doses >20 mg/day prednisone equivalent or steroids given with anti-neoplastic intent within 7 days prior to first dose of study drug.
    2. Chemotherapy or radiotherapy within 4 weeks.
    3. Monoclonal antibody within 4 weeks.
    4. Investigational therapy within 4 weeks.
    5. Chinese patent medicine with anti-neoplastic intent within 4 weeks.
  14. Not recovered from toxicity of any prior anti-cancer therapy to ≤ Grade 1, except for alopecia, ANC, Hgb and platelets. For ANC, Hgb and platelets, see inclusion criterion #5.
  15. Prior malignancy within the past 3 years, except for curatively treated basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast.
  16. Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, symptomatic inflammatory bowel disease, history of bariatric surgery, or partial or complete bowel obstruction.
  17. Major surgery within 4 weeks prior to first dose of study treatment.
  18. Active fungal, bacterial and/or viral infection requiring systemic therapy.
  19. Known infection with human immunodeficiency virus (HIV), or serologic status reflecting active hepatitis B or C infection as follows:

    1. Presence of hepatitis B surface antigen (HBsAg) or anti-hepatitis B core antibody (anti-HBc). participants with presence of anti-HBc, but absence of HBsAg, are eligible if hepatitis B virus (HBV) DNA is < 500 IU/mL, anti-viral therapy started before the first dose of study treatment, and if they are willing to undergo monthly monitoring for HBV reactivation.
    2. Presence of hepatitis C virus (HCV) antibody. participants with presence of HCV antibody are eligible if HCV RNA is undetectable (<15 IU/mL).
  20. Pregnant or lactating women.
  21. Underlying medical conditions that, in the investigator's opinion, will render the administration of study drug hazardous or obscure the interpretation of toxicity or AEs.
  22. Concurrent participation in another therapeutic clinical trial.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03520920


Locations
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China, Heilongjiang
Harbin Medical University Cancer Hospital
Harbin, Heilongjiang, China
China, Hubei
Tongji Hospital, Tongji Medical college of HUST
Wuhan, Hubei, China
China, Jiangsu
The Affiliated Hospital of Xuzhou Medical University
Xuzhou, Jiangsu, China
China, Shanghai
Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Mdicine
Shanghai, Shanghai, China
Sponsors and Collaborators
BeiGene
Investigators
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Principal Investigator: Meng Ji, MD BeiGene (Beijing) Co.,
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Responsible Party: BeiGene
ClinicalTrials.gov Identifier: NCT03520920    
Other Study ID Numbers: BGB-3111-213
CTR20170965 ( Registry Identifier: Center for drug evaluation, CFDA )
First Posted: May 11, 2018    Key Record Dates
Last Update Posted: September 30, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, B-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Rituximab
Zanubrutinib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action