Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma MedDRA version: 20.1 Level: LLT Classification code 10041152 Term: Small lymphocytic lymphoma, consistent with CLL (Working Formulation) System Organ Class: 100000004864 MedDRA version: 20.1 Level: LLT Classification code 10008976 Term: Chronic lymphocytic leukemia System Organ Class: 100000004864
Conditions
Interventions
Product Name: Zanubrutinib
Product Code: BGB-3111
Pharmaceutical Form: Capsule
INN or Proposed INN: Zanubrutinib
CAS Number: 1691249-45-2
Current Sponsor code: BGB-3111
Other descriptive name: BGB-31
Sponsors
BeiGene, Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Each patient eligible to participate in this study must meet ALL of the following criteria: 1. Age 18 years or older 2. Confirmed diagnosis of CLL or SLL that meets the IWCLL criteria 3. CLL/SLL requiring treatment as defined by at least 1 of the following criteria: a. Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia b. Massive (= 6 cm below left costal margin), progressive, or symptomatic splenomegaly c. Massive nodes (= 10 cm in longest diameter), or progressive or symptomatic lymphadenopathy d. Progressive lymphocytosis with an increase of > 50% over a 2 month period or lymphocyte doubling time of 100.5ºF or 38ºC for = 2 weeks without other evidence of infection iv. Night sweats for > 1 month without evidence of infection 4. Relapsed or refractory to at least 1 prior systemic therapy for CLL/SLL. A line of therapy is defined as completing at least 2 cycles of treatment of standard regimen according to current guidelines or of an investigational regimen on a clinical trial 5. Measurable disease by CT/magnetic resonance imaging (MRI). Measurable disease is defined as = 1 lymph node > 1.5 cm in longest diameter and measurable in 2 perpendicular diameters 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 7. Life expectancy = 6 months 8. Adequate bone marrow function as defined by: a. Absolute neutrophil count (ANC) = 1000/mm3 (growth factor use is allowed), except for patients with bone marrow involvement in which case ANC must be = 750/mm3 b. Platelet = 75,000/mm3 (may be post-transfusion), except for patients with bone marrow involvement by CLL in which case the platelet count must be = 50,000/mm3 9. Patient must have adequate organ function defined as: a. Creatinine clearance = 30 mL/min (as estimated by the Cockcroft-Gault equation or the Modification of Diet in Renal Disease [MDRD] equation, or as measured by nuclear medicine scan or 24 hour urine collection) b. Aspartate aminotransferase/serum glutamic oxaloacetic transaminase, and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase = 2.5 × upper limit of normal unless due to CLL/SLL c. Serum total bilirubin < 3.0 × upper limit of normal (unless documented Gilbert’s syndrome) 10. Female patients of childbearing potential must practice highly effective methods (Section 5.1.2) 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 ibrutinib 11. Male patients are eligible if vasect
Exclusion criteria
Exclusion criteria: Each patient eligible to participate in this study must NOT meet any of the following exclusion criteria: 1. Known prolymphocytic leukemia or history of, or currently suspected, Richter’s transformation (biopsy based on clinical suspicion may be needed to rule out transformation) 2. Clinically significant cardiovascular disease including the following: a. Myocardial infarction within 6 months before screening b. Unstable angina within 3 months before screening c. New York Heart Association class III or IV congestive heart failure d. History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, Torsades de Pointes) e. QTcF > 480 milliseconds based on Fridericia’s formula f. History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place g. Uncontrolled hypertension as indicated by a minimum of 2 consecutive blood pressure measurements showing systolic blood pressure > 170 mmHg and diastolic blood pressure > 105 mmHg at screening 3. 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 4. 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 5. History of stroke or intracranial hemorrhage within 180 days before first dose of study drug 6. Severe or debilitating pulmonary disease 7. 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 8. Active fungal, bacterial, and/or viral infection requiring systemic therapy 9. Known central nervous system involvement by leukemia or lymphoma 10. 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 11. Known infection with HIV or serologic status reflecting active viral hepatitis B or C infection as follows: a. Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Patients with presence of HBcAb, but absence of HBsAg, are eligible if hepatitis B virus (HBV) DNA is undetectable (< 20 IU), and if they are willing to undergo monitoring for HBV reactivation b. Presence of hepatitis C virus (HCV) antibody. Patients with presence of HCV antibody are eligible if HCV RNA is undetectable 12. Moderate or severe hepatic impairment, ie, Child-Pugh class B or C 13. Major surgery within 4 weeks of the first dose of study drug 14. Prior treatment with a BTK inhibitor 15. Last dose of prior therapy for CLL/SLL = 14 days before randomization, with the following additional exclusion requirements: a. Treatment with monoclonal antibody-based therapy within 28 days of first dose of study drug b. Treatment with chimeric antigen receptor T-cell therapy within 180 days of first dose of study drug c. Treatment with Chinese herbal medicine with anticancer intent within 28 days of first dose of study drug d. Chemotherapy or radiation treatment within 21 days of first dose of study drug or hematopoietic stem cell transplantation within 90 days of first dose of study drug 16. Prior steroid u
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: ? To compare the efficacy of zanubrutinib versus ibrutinib as measured by: o Progression-free survival determined by independent central review o Progression-free survival determined by investigator assessment o Duration of response as determined by independent central review o Duration of response as determined by investigator assessment o Time to treatment failure o Rate of partial response with lymphocytosis or higher determined by independent central review o Overall survival o Patient-reported outcomes ? To compare the safety of zanubrutinib versus ibrutinib ;Primary end point(s): The primary endpoint is ORR determined by independent central review using the “modified” 2008 IWCLL guidelines with modification for treatment-related lymphocytosis for patients with CLL and per Lugano Classification for non-Hodgkin lymphoma (NHL) for patients with SLL. ;Timepoint(s) of evaluation of this end point: The final analysis will occur approximately 12 months after 400 patients have been randomized. ;Main Objective: To compare the efficacy of zanubrutinib versus ibrutinib as measured by overall response rate determined by independent central review | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Endpoint: - PFS, defined as the time from randomization to the date of first documentation of disease progression or death, whichever occurs first, determined by independent central review Other Secondary Endpoints: - PFS determined by investigator assessment - Duration of response, 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, determined by independent central review - Duration of response by investigator assessment - Time to treatment failure, defined as time from randomization to discontinuation of study drug due to any reason - Rate of PR-L or higher, defined as the proportion of patients who achieve a CR/CRi + PR + nodular PR + PR-L determined by independent central review - Overall survival, defined as the time from randomization to the date of death due to any cause - PROs measured by the EQ-5D-5L and EORTC QLQ-C30 questionnaires - Safety parameters, including AEs, SAEs, clinical laboratory tests, physical exams, and vital signs ;Timepoint(s) of evaluation of this end point: The final analysis will occur approximately 12 months after 400 patients have been randomized. | — |
Countries
Australia, Belgium, China, Czech Republic, France, Germany, Italy, Netherlands, New Zealand, Poland, Spain, Sweden, Turkey, United Kingdom, United States
Contacts
Public ContactBeiGene Clinical Support
BeiGene, Ltd.
Outcome results
None listed