None listed
Conditions
Interventions
Drug : Two Combination Drugs
1) Sonrotoclax (BGB-11417) – Once daily, taken orally:
Phase A: 40 ? 80 ? 160 mg daily (28-day cycle)
Phase B: 80 ? 160 ? 320 mg daily (28-day cycle)
Phase C: 160 ? 320 ?
Sponsors
Yonsei University Health System, Severance Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of signed and dated written informed consent prior to any study-specific procedures, sampling, or analyses 2. Age 19 years or older 3. Confirmed diagnosis (per World Health Organization [WHO] guidelines, unless otherwise noted) of Primary Central Nervous System Lymphoma (PCNSL) i. R/R PCNSL defined as disease that relapsed after, or was refractory to, at least 1 prior High Dose Methotrexate (HD-MTX)based systemic therapy ii. Active disease requiring treatment 4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 5. Adequate organ function defined as: a. Absolute neutrophil count (ANC) = 1.0 x 109/L without growth factor support – filgrastim within 5 days or other growth factor (eg, pegfilgrastim) within 10 days of blood test. b. Platelets > 75x 109/L (> 75,000/mm3) without growth factor support within 28 days or transfusion within 7 days of blood test. c. Hemoglobin > 7.5 g/L with or without growth factor support or transfusion. d. Adequate kidney function defined as: Creatinine clearance or glomerular filtration rate (GFR) = 50 mL/min as estimated by one of the following: i. Cockcroft-Gault equation i. Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation i. 24-hour urine collection e. Adequate liver function indicated by Adequate liver function as indicated by aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5 x the institutional upper limits of normal (ULNs) value; serum total bilirubin 12 weeks 9. Able to comply with the requirements of the study
Exclusion criteria
Exclusion criteria: 1. Prior malignancy (other than the disease under study) within the past 2 years, except for curatively treated skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score = 6 prostate cancer 2. Underlying medical conditions that, in the investigator’s opinion, will render the administration of study drug hazardous or obscure the interpretation of safety or efficacy results 3. Prior allogeneic stem cell transplant or autologous stem cell transplant unless = 3 months after transplant; or prior chimeric antigen receptor T-cell (CAR-T) therapy unless = 3 months after cell infusion 4. Use of the following substances prior to the first dose of study drug: a. = 28 days before the first dose of study drug: i. Any biologic and/or immunologic-based therapy(ies) including experimental therapy(ies) for leukemia, lymphoma, or myeloma (including, but not limited to, monoclonal antibody therapy, eg, cancer vaccine therapy) b. = 14 days before the first dose of study drug: i. Systemic chemotherapy or radiation therapy c. = 7 days before the first dose of study drug: i. Corticosteroid given with antineoplastic intent other than control of BTK inhibitor withdrawal flare d. = 5 half-lives (or 3 days – whichever is shorter) before the first dose of study drug: i. BTK inhibitor, tyrosine kinase inhibitor, or other targeted small molecule given with antineoplastic intent. 5. Active fungal, bacterial, and/or viral infection requiring systemic therapy Note: Oral antibiotics for minor bacterial infections are allowed. 6. Prior therapy = 2 months with or progression on a venetoclax or ibrutinib 7. Major surgery = 4 weeks before the first dose of study treatment 8. Toxicity from prior anticancer therapy that has not recovered to = Grade 1 (except for alopecia, ANC, and platelet count; for ANC and platelet count, see inclusion criterion 6) 9. Clinically significant cardiovascular disease including the following: a. Myocardial infarction = 6 months before screening b. Unstable angina = 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. Heart rate-corrected QT interval > 480 milliseconds based on Bazett 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, at screening, showing systolic blood pressure > 170 mmHg and diastolic blood pressure > 105 mmHg 10. Known infection with human immunodeficiency virus (HIV), or serologic status reflecting active viral hepatitis B (HBV), or viral hepatitis C (HCV) infection as follows: a. Presence of HIV are excluded b. Presence of viral hepatitis B surface antigen (HBsAg) or viral hepatitis B core antibody (HBcAb) Note: Patients with presence of HBcAb, but absence of HBsAg, are eligible if HBV DNA is undetectable and if they are willing to undergo monitoring for HBV reactivation (see Section 6.12.6). c. Presence of HCV antibody Note: Patients with presence of HCV antibody are eligible if HCV RNA is undetectable and if they are willing to undergo monitoring for HCV reactivation (see Section 6.12.6). 11. Pregnant, planning to become pregnant, or lactating women 12. Unable to swallow capsules or disease significantly affecting gastrointesti
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1: Dose Finding Primary Objectives • Determine the safety and tolerability and define the maximum tolerated dose (MTD) (or maximum assessed dose [MAD]) and the recommended Phase 2 dose (RP2D) of sonrotoclax in combination with zanubrutinib Part 2: Expansion Primary Objectives • Further evaluate the safety and tolerability of the combination of sonrotoclax and zanubrutinib in the target patient population • Evaluate the antitumor activity of the combination of sonrotoclax and zanubrutinib as measured by overall response rate (ORR) after two cycles of therapy | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Objectives • Examine duration of response (DOR), 2-year progression free survival (PFS) rate, and 2-year overall survival (OS) • Rate of successful stem cell harvest and proportion of patients proceeding to high-dose therapy and autologous stem cell transplant (ASCT) Exploratory Objectives • To assess peripheral blood (PB) and cerebral spinal fluid (CSF)-based immunologic biomarker characteristics and correlation with preliminary antitumor activity • To evaluate the drug concentration of CSF • To assess neurocognitive function (appendix 3. K-MMSE | — |
Countries
Korea, Republic of
Contacts
Public ContactJIN SEOK kim
Yonsei University Health System, Severance Hospital
Outcome results
None listed