chronic lymphocytic leukemia/small lymphocytic lymphoma MedDRA version: 21.0 Level: LLT Classification code 10008976 Term: Chronic lymphocytic leukemia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: imbruvica
Product Name: NA
Product Code: [NA]
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: IBRUTINIB
CAS Number: 936563-96-1
Current Sponsor code: NA
Concentration unit: mg mill
Sponsors
OSPEDALE SAN RAFFAELE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age =18 years 2. Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocyte lymphoma (SLL) according to iwCLL diagnostic criteria 3. Previously untreated active disease requiring treatment according to iwCLL criteria 4. ECOG PS 0 or 1 5. Lymph node disease measurable (longest diameter> 1.5 cm) by CT 6. Adequate blood count 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 7. Adequate liver and kidney 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 increased bilirubin is due to Gilbert's syndrome or of non-hepatic origin) 8. Prothrombin time (PT) / International normal ratio (INR) =65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 1. Any prior therapy (including but not limited to chemotherapy, targeted therapy, immunomodulatory therapy, radiotherapy, and / or monoclonal antibody) used to treat CLL or SLL. 2. Patients with del (17p) and / or TP53 mutation according to centralized laboratory assessment. 3. History of other malignancies, except: ¿ Malignant tumor treated with curative intent and with no known active disease present for =3 prior to first dose of study drug and deemed low risk of recurrence by treating physician ¿ Malignant skin neoplasm not adequately treated or lentigo maligna with no evidence of disease ¿ Adequately treated carcinoma in situ with no evidence of disease. 4. Known or suspected history of Richter's transformation. 5. Known hypersensitivity to one or more study drugs. 6. Known bleeding disorders (eg von Willebrand disease or haemophilia). 7. History of stroke or intracranial haemorrhage within 6 months prior to enrollment. 8. Known history of human immunodeficiency virus (HIV) or active hepatitis C virus (HCV) or hepatitis B virus (HBV) infection. Individuals who are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) result before enrollment. Those who test positive for PCR will be excluded. 9. Inability to swallow capsules / tablets or malabsorption syndrome, any disease that significantly affects gastrointestinal function, or resection of the stomach or small intestine, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction. 10. Concomitant use of warfarin or other vitamin K antagonists. 11. Major surgery within 4 weeks of the first dose of study drug
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the percentage of BM MRD <10-4 in BM at +30 days of follow-up after ibrutinib (Cycles 1-24) and obinutuzumab (Cycle 13 Days 1,2,8,15; Cycles 14-18 Day 1);Secondary Objective: ¿ To evaluate the response to treatment after ibrutinib (Cycles 1-24) and obinutuzumab (Cycle 13 Days 1,2,8,15; Cycles 14-18 Day 1); ¿ Evaluate PFS after ibrutinib (Cycles 1-24) and obinutuzumab (Cycle 13 Days 1,2,8,15; Cycles 14-18 Day 1); ¿ To evaluate OS after ibrutinib (Cycles 1-24) and obinutuzumab (Cycle 13 Days 1,2,8,15; Cycles 14-18 Day 1); ¿ Evaluate the response to retreatment with ibrutinib monotherapy in patients who experience disease recurrence after discontinuation of treatment; ¿ To study the safety and tolerance of the combined treatment with a limited duration (treatment and post-treatment period) and compare the results with historical controls.;Primary end point(s): Percentage of patients with MRD <10-4 in BM at +30 follow-up days after completion of therapy;Timepoint(s) of evaluation of this end point: 30 days after completion of therapy | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety and tolerance; Overall response (partial response, partial response with lymphocytosis and complete response); Percentage of MRD undetectable at Cycle 13 Day 1 (before the start of obinutuzumab), Cycle 19 Day 1 (at the end of treatment with obinutuzumab); Percentage of complete responses; Progression-free survival; Overall survival; Overall response rate to Ibrutinib retreatment to relapse;Timepoint(s) of evaluation of this end point: during treatment and follow up period; during treatment and follow up period; during treatment; during treatment period and follow up period; duirng follow up period; during treatment period and follow up period; during follow up period | — |
Countries
Italy
Contacts
Public ContactUfficio Data Management PS-CLL
Ospedale San Raffaele
Outcome results
None listed