Acalabrutinib and High Frequency Low Dose Subcutaneous Rituximab in Patients With Previously Untreated Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma

Exclusion Criteria

• •1. Patients receiving cancer therapy (i.e., chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy, surgery).
• •a. Systemic corticosteroid therapy started prior to study entry is allowed as clinically warranted. Topical or inhaled corticosteroids are permitted.
• •2. Serologic status reflecting active hepatitis B or C infection. Patients 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. 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.
• •3. Known history of HIV.
• •4. Known histological transformation from CLL to an aggressive lymphoma.
• •5. Evidence of ongoing systemic bacterial, fungal or viral infection, except localized fungal infections of skin or nails. NOTE: Patients may be receiving prophylactic antiviral or antibacterial therapies at investigator discretion.
• •6. Live virus vaccines within 4 weeks prior to C1D1 or during rituximab therapy.
• •7. History of anaphylaxis (excluding infusion related reactions) in association with previous anti-CD20 administration or acalabrutinib.
• •8. Any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
• •1. Symptomatic, or history of documented congestive heart failure (NY Heart Association functional classification III-IV)
• •2. Uncontrolled cardiac arrhythmia (Patients with controlled atrial fibrillation/flutter are eligible)
• •3. Myocardial infarction within 3 months of enrollment
• •4. Angina not well-controlled by medication
• •5. Poorly controlled or clinically significant atherosclerotic vascular disease including cerebrovascular accident (CVA), transient ischemic attack (TIA), angioplasty, cardiac/vascular stenting within 3 months of enrollment.
• •6. Active bleeding or history of bleeding diathesis (eg, hemophilia or von Willebrand disease).
• •7. Any history of intracranial bleed or stroke within 6 months of first dose of study drug
• •8. Patients with suspected or confirmed PML
• •9. Patients with malabsorption syndrome or gastrointestinal disease that limits absorption of oral medication
• •9. Malignancy within 2 years of study enrollment except for adequately treated basal, squamous cell carcinoma or non-melanomatous skin cancer, carcinoma in situ of the cervix, superficial bladder cancer not treated with intravesical chemotherapy or BCG within 6 months, localized prostate cancer and PSA \<1.0 mg/dL on 2 consecutive measurements at least 3 months apart with the most recent one being within 4 weeks of study entry.
• •10. Patients with active uncontrolled autoimmune hemolytic anemia or ITP.
• •11. Inability to discontinue use of strong CYP3A inhibitors. Patients taking moderate CYP3A inhibitors or strong CYP3A inducers are eligible.
• •12. Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) within 7 days of first dose of study drug.
• •13. Requires treatment with proton pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole) at study entry. Subjects receiving proton pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrollment to this study.