Fixed-duration Therapy With Ibrutinib and Obinutuzumab (GA-101) in Treatment-naïve Patients With CLL
This is a phase 2 multicenter national interventional pharmacological study aimed at determining the efficacy of a fixed duration treatment with ibrutinib and obinutuzumab in terms of uMRD in the BM at the end of treatment (+30 Days follow-up). Treatment with ibrutinib and obinutuzumab will be administered according to the following schedule: Ibrutinib 420 mg QD for 24 months (Cycles 1-24) Obinutuzumab starting from Cycle 13 Day 1 (100 mg Cycle 13 Day 1, 900 mg Cycle 13 Day 2, 1000 mg Cycle 13 Days 8 and 15, 1000 mg Cycles 14-18 Day 1). At the end of Cycle 24 all responding patients will discontinue ibrutinib and proceed with follow-up. If disease relapse occurs at any time after discontinuing treatment, ibrutinib therapy will be reintroduced at the standard dose of 420 mg QD and response to treatment monitored over time. Patients with stable (SD) or progressive disease (PD) at the end of Cycle 24, will continue ibrutinib as long as the treating physician deems they are benefiting from treatment and will be followed up in the study for survival and response to subsequent therapies.
• Age ≥18 years
• Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that meets iwCLL diagnostic criteria
• Previously untreated active disease requiring treatment per iwCLL criteria
• ECOG PS 0 or 1
• Measurable lymph node disease (\>1.5 cm longest diameter) by CT scan
• Adequate hematologic function defined as:
‣ Absolute neutrophil count (ANC) \>750 cells/μL (750 cells/mm3 or 0.75 x 109/L)
⁃ Platelet count \>30,000/μL (30,000 cells/mm3 or 30 x 109/L)
⁃ Hemoglobin \>8.0 g/dL
• Adequate hepatic and renal function defined as:
‣ Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≤3.0 x upper limit of normal (ULN)
⁃ Estimated Creatinine Clearance (CrCl) ≥30 mL/min (Cockcroft- Gault)
⁃ Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
• Prothrombin time (PT)/International normal ratio (INR) \<1.5 x ULN and PTT (activated partial thromboplastin time \[aPTT\]) \<1.5 x ULN (unless abnormalities are unrelated to coagulopathy or bleeding disorder).