Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma MedDRA version: 20.0 Level: LLT Classification code 10003946 Term: B-Lymphocytic, CLL (Kiel Classification) System Organ Class: 100000004864 MedDRA version: 20.1 Level: LLT Classification code 10041152 Term: Small lymphocytic lymphoma, consistent with CLL (Working Formulation) System Organ Class: 100000004864
Conditions
Interventions
Product Name: BGB-3111
Product Code: BGB-3111
Pharmaceutical Form: Capsule
INN or Proposed INN: not yet established
CAS Number: 1691249-45-2
Current Sponsor code: BGB-3111
Concentration unit: mg milli
Sponsors
BeiGene, Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Unsuitable for chemoimmunotherapy with FCR in the opinion of the investigator 2. Confirmed diagnosis of CD20-positive CLL or SLL that meets the CLL criteria (Hallek et al, 2008) 3. Binet Stage C disease, or Binet Stage B or A disease requiring treatment as defined by at least one of the criteria (Hallek et al, 2008) 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 5. Life expectancy = 6 months 6. Adequate bone marrow function 7. Patient must have adequate organ function 8. 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, 3 months after the last dose of bendamustine, or 12 months after the last dose of rituximab, whichever is longer. 9. Male patients are eligible if vasectomized or if they agree to the use of barrier contraception with other methods described above during the study treatment period and for = 90 days after the last dose of BGB-3111 or 3 months after the last dose of bendamustine whichever is longer. 10. Ability to provide written informed consent and can understand and comply with the requirements of the study Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 93 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 374
Exclusion criteria
Exclusion criteria: 1. Previous systemic treatment for CLL/SLL 2. Known prolymphocytic leukemia or history of, or currently suspected, Richter’s transformation 3. Clinically significant cardiovascular disease 4. 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 5. History of severe bleeding disorder 6. History of stroke or intracranial hemorrhage within 6 months before first dose of study drug 7. Severe or debilitating pulmonary disease 8. Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction 9. Active fungal, bacterial and/or viral infection requiring systemic therapy 10. Known central nervous system involvement by leukemia or lymphoma 11. 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 12. Known infection with HIV, or serologic status reflecting active hepatitis B or C infection 13. Major surgery within 4 weeks of the first dose of study drug 14. Pregnant or lactating women 15. Vaccination with a live vaccine within 35 days prior to the first dose of study drug 16. Ongoing alcohol or drug addiction 17. Hypersensitivity to BGB-3111, bendamustine, or rituximab or any of the other ingredients of the study drugs 18. Requires ongoing treatment with a strong CYP3A inhibitor or inducer 19. Concurrent participation in another therapeutic clinical trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare efficacy between treatment groups in cohort 1, as measured by progression-free survival determined by independent central review;Secondary Objective: To evaluate efficacy in cohort 1, as measured by the following: o Overall response rate determined by independent central review and by investigator assessment o Overall survival o Duration of response determined by independent central review and by investigator assessment o Progression-free survival determined by investigator assessment o Patient-reported outcomes • To evaluate efficacy in cohort 2 (patients with del[17p]), as measured by the following: o Overall response rate determined by independent central review o Overall survival o Progression-free survival determined by independent central review o Duration of response determined by independent central review • To compare safety between the treatment groups in cohort 1 • To evaluate pharmacokinetics of BGB-3111;Primary end point(s): The primary endpoint is progression-free survival in cohort 1 (patients without del[17p]) determined by independent central review using the iwCLL guidelines with modification for treatment-related lymphocytosis, and defined as the time from randomization to the date of first documentation of disease progression or death, whichever occurs first.;Timepoint(s) of evaluation of this end point: 1 interim analysis of progression-free survival by independent central review in cohort 1, performed when approximately 79 events (67% of the target number of events at final analysis) from the arms A and B are observed. It is estimated that it will take approximately 25 months to observe 79 events. The final analysis of progression-free survival will take place after 118 events are observed, which is estimated as approximately 35 months from study start. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Overall response rate in cohort 1 defined as the proportion of patients who achieve a complete response, complete response with incomplete bone marrow recovery, partial response, or partial response with lymphocytosis, determined by independent central review and by investigator assessment • Overall survival in cohort 1 defined as the time from randomization to the date of death due to any reason • Duration of response in cohort 1 determined by independent central review and by investigator assessment using the iwCLL criteria with modification for treatment-related lymphocytosis, and defined as the time from the date that response criteria are first met to the date that disease progression is objectively documented or death, whichever occurs first • Progression-free survival in cohort 1 determined by investigator assessment • Patient-reported outcomes in cohort 1 measured by the EQ-5D-5L and EORTC QLQ-C30 questionnaires • Overall response rate in cohort 2 (patients with del[17p]) determined by independent central review • Overall survival in cohort 2 • Progression-free survival in cohort 2 determined by independent central review • Duration of response in cohort 2 determined by independent central review • Safety parameters, including AEs, SAEs, clinical laboratory tests, physical exams, and vital signs • Pharmacokinetic parameters such as apparent clearance of the drug from plasma (CL/F) and AUC0-12;Timepoint(s) of evaluation of this end point: At time of interim analysis if the PFS comparison between the 2 arms in cohort 1 crosses the stopping boundary. Or at the time of final PFS analysis. | — |
Countries
Australia, Austria, Belgium, Canada, Czech Republic, France, Germany, Hungary, Israel, Italy, Korea, Republic of, Netherlands, New Zealand, Poland, Russian Federation, Spain, Sweden, Taiwan, United Kingdom, United States
Contacts
Public ContactUS
BeiGene, Ltd.
Outcome results
None listed