Bruton's Tyrosine Kinase (BTK) Inhibition in B-cell Lymphomas

Exclusion Criteria

• •1. Previous treatment with a BTK inhibitor
• •2. Patients who progressed or became refractory while on treatment with a phosphoinositide 3-kinase (PI3K) inhibitors
• •3. Inability to tolerate 4 courses of high dose ara-C / platin compound, especially if due to underlying comorbidities
• •4. History of stroke or intracranial hemorrhage within 6 months prior to the first dose of study drug
• •5. Major surgery, within 4 weeks prior to the first dose of study drug
• •6. Known bleeding diathesis
• •7. Condition that requires therapeutic anticoagulation with Vitamin K antagonists
• •8. Condition that requires treatment with a strong cytochrome P450 3A4/5 (CYP3A4/5) inhibitor
• •9. Any life-threatening illness, serious medical condition, laboratory abnormality, organ system dysfunction or psychiatric illness which, in the investigator's opinion, could compromise the patient's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk and that would prevent the patient from signing the informed consent form
• •10. Known central nervous system or meningeal involvement by lymphoma
• •11. Contraindication to any drug contained in these regimen
• •12. Known history of human immunodeficiency virus (HIV)
• •13. Known active Hepatitis C Virus (HCV; RNA polymerase chain reaction (PCR)-positive) or active Hepatitis B Virus infection (HBs Ag positive or DNA PCR-positive) or any uncontrolled active systemic infection requiring intravenous (IV) antibiotics. Patients with PCR-negative for hepatitis B virus (HBV) are permitted in the study.
• •14. Left ventricular ejection fraction (LVEF) \< 45% as determined by echocardiography or multiple uptake gated acquisition (MUGA) scan
• •15. Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months prior to the first dose of study drug, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification
• •16. Any of the following biochemical values within 14 days prior to inclusion and prior to the first dose of study drug :
• •1. Serum glutamic-oxaloacetic transaminase/aspartate aminotransferase (SGOT/ASAT) or serum glutamic-pyruvic transaminase/alanine aminotransferase (SGPT/ALAT) \> 3.0 x upper limit of normal (ULN)
• •2. Serum total bilirubin \> 2.0 mg/dL (34 µmol/L), except in patients with hemolytic anemia or with Gilbert syndrome,
• •3. Calculated creatinine clearance of \< 50 mL /min (for patients who will have DHAOx chemotherapy) or \< 70 mL/min (for patients who will have DHAP chemotherapy)
• •17. Patients with pre-existing ≥ Grade 2 neuropathy
• •18. Prior history of malignancies other than lymphoma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the patient has been free of the disease for ≥ 3 years
• •19. Use of any standard or experimental anti-cancer drug therapy within 28 days prior to the first dose of study drug
• •20. Women who are pregnant or breastfeeding
• •21. Medical history of hepatic chronic disease whatever the anteriority
• •22. Sinusoidal obstruction syndrome (Veno-Occlusive Disease (VOD)) whatever the anteriority