Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

BTK Inhibitor BGB-3111 in Chinese Patients 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 : Active, not recruiting
First Posted : May 11, 2018
Last Update Posted : November 4, 2019
Sponsor:
Information provided by (Responsible Party):
BeiGene

Tracking Information
First Submitted Date  ICMJE April 28, 2018
First Posted Date  ICMJE May 11, 2018
Last Update Posted Date November 4, 2019
Actual Study Start Date  ICMJE January 4, 2018
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 28, 2018)
overall response rate(ORR) [ Time Frame: up to 2 years ]
The achievement of either a partial response (PR) or complete response (CR)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 28, 2018)
  • 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 IWG on NHL criteria) or death, whichever comes first
  • 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.
  • Overall survival (OS) [ Time Frame: up to 2 years ]
    Defined as the time from first dose of BGB-3111 until death.
  • 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.
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE BTK Inhibitor BGB-3111 in Chinese Patients With Large B-Cell Lymphoma (Non-GCB) and Indolent Lymphoma (FL and MZL)
Official Title  ICMJE 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
Brief Summary Screening (up to 28 days); BGB-3111160 mg twice daily in combination with rituximab until disease progression, discontinued treatment due to intolerance, died, withdrew from study, or completed study treatment for a total of 2 years, treatment (up to 2 years), safety follow up (30 days); survival follow-up until patient death or study termination by the Sponsor.
Detailed Description

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 Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (non-GCB Subtype) and Relapsed/Refractory Indolent Lymphoma (Follicular Lymphoma and Marginal Zone Lymphoma).

The study is composed of two cohorts. Cohort 1 will be approximately 20 subjects and Cohort 2 will be approximately 20 subjects.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Marginal Zone Lymphoma
  • Follicular Lymphoma
  • Diffuse Large B-Cell Lymphoma
Intervention  ICMJE Drug: BGB-3111
  1. BGB-3111 at a dose of 160 mg orally (PO) twice daily (BID)
  2. Rituximab will be administered at 375 mg/m2 intravenously on Cycle 1 Days 1, 8, 15, 22, and on Day 1 of Cycles 4, 6, 8, 10.
Other Name: Rituximab
Study Arms  ICMJE Experimental: cohort 1 and cohort 2
BGB-3111 in combination with Rituximab in relapsed/refractory non-GCB DLBCL and relapsed/refractory follicular (FL) or marginal zone lymphoma (MZL)
Intervention: Drug: BGB-3111
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: April 28, 2018)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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. Patients 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 ii. Relapsed disease (disease progression after most recent therapy for DLBCL) 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; 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 aPTT ≤ 1.5x ULN. Patients 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. LVEF ≥ 50%.
  • 7. Life expectancy ≥ 6 months.
  • 8. Eastern Cooperative Oncology Group performance status of 0, 1, or 2.
  • 9. Female patients 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 BGB-3111, or 12 months after the last dose of rituximab, whichever is longer.
  • 10.Male patients 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 BGB-3111.
  • 11.Able to provide written informed consent and can understand and comply with the requirements of the study.

Exclusion Criteria:

  • 1. Known central nervous system lymphoma or leukemia.
  • 2. Histological confirmed gastric 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 BTK inhibitor treatment.
  • 10. Requires ongoing treatment with a strong 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). Patients 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. Patients 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03520920
Other Study ID Numbers  ICMJE BGB-3111-213
CTR20170965 ( Registry Identifier: Center for drug evaluation, CFDA )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party BeiGene
Study Sponsor  ICMJE BeiGene
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jianfeng Zhou, MD Tongji Hospital
PRS Account BeiGene
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP