Acalabrutinib With Rituximab and Lenalidomide in Relapsed/Refractory B-cell Non-Hodgkin Lymphoma

Exclusion Criteria

• •1. Diagnosed with mantle cell lymphoma
• •2. Previously treated with more than four lines of chemotherapy (Consolidative autologous stem cell transplantation is deemed as the same line therapy)
• •3. Previously treated with allogeneic hematopoietic stem cell transplantation within 6 months
• •4. GVHD requiring treatment
• •5. Patient who cannot take drug per oral
• •6. Known resistance to both BTK inhibitor and lenalidomide (Progression free survival to both BTK inhibitor and lenalidomide \< 6 months)
• •7. Known resistant mutation to BTK inhibitor (BTKC481S and PLGCR665W)
• •8. Prior malignancy (or any other malignancy that requires active treatment), except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for ≥ 5 years or which will not limit survival to \< 5 years.
• •9. Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification. Subjects with controlled, asymptomatic atrial fibrillation during screening can enroll on study.
• •10. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
• •11. Known history of infection with HIV or any uncontrolled active systemic infection (eg, bacterial, viral or fungal).
• •12. Known history of drug-specific hypersensitivity or anaphylaxis to study drug (including active product or excipient components).
• •13. Active bleeding, history of bleeding diathesis (eg, hemophilia or von Willebrand disease).
• •14. Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic purpura).
• •15. Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer.
• •16. Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) within 7 days of first dose of study drug.
• •17. Prothrombin time/INR or aPTT (in the absence of Lupus anticoagulant) \> 2x ULN.
• •18. Requires treatment with proton pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Subjects receiving proton pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrollment to this study.
• •19. History of significant cerebrovascular disease or event, including stroke or intracranial hemorrhage, within 6 months before the first dose of study drug.
• •20. Major surgical procedure within 28 days of first dose of study drug. Note: If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug.
• •21. Hepatitis B or C serologic status: subjects who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR). Those who are hepatitis B surface antigen (HbsAg) positive or hepatitis B PCR positive will be excluded. Those who are positive only for anti-HBc and negative for HbsAg and hepatitis B PCR need to receive adequate antiviral prophylaxis for hepatitis B during the study period.
• •Subjects who are hepatitis C antibody positive will need to have a negative PCR result. Those who are hepatitis C PCR positive will be excluded.
• •23. Uncontrolled active infection as determined by the investigator.
• •24. WBC \< 3,000 /μL, ANC \< 1,000 /μL, Platelets \< 75,000 /μL, or Hemoglobin \< 9.0 g/dL. Correction with transfusion within 2 weeks is not allowed.
• •25. Total bilirubin \> 2 x ULN, or AST, ALT \> 3 x ULN
• •26. Cr \> 1.5 x ULN or CLcr \< 30 mL/min/1.73m2
• •27. Breastfeeding or pregnant.
• •28. Concurrent participation in another therapeutic clinical trial.