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

Inclusion Criteria

• Diagnosis of B-cell CLL or SLL, with diagnosis established according to IWCLL criteria and documented within medical records. Patients must not have received previous therapy for CLL/SLL
• CLL/SLL that warrants treatment consistent with accepted IWCLL criteria for initiation of therapy. Any one of the following conditions constitutes CLL/SLL that warrants treatment:
• Evidence of progressive marrow failure as manifested by the onset or worsening of anemia and/or thrombocytopenia, or
• Massive (i.e., lower edge of spleen ≥6 cm below the left costal margin), progressive, or symptomatic splenomegaly, or
• Massive (i.e., ≥10 cm in the longest diameter), progressive, or symptomatic lymphadenopathy, or
• Progressive lymphocytosis in the absence of infection, with an increase in blood absolute lymphocyte count (ALC) ≥50% over a 2-month period or lymphocyte doubling time of 100.5°F or 38.0°C for ≥2 weeks, or

iv. Drenching night sweats for >1 month.

• Adequate organ system function, defined as follows:
• Absolute neutrophil count (ANC) ≥ 0.5x109/L and platelet count ≥ 30x109/L
• Total bilirubin ≤2.5 times the upper limit of normal (ULN) unless due to Gilbert's disease
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x ULN if no liver involvement or ≤5 x the ULN if known liver involvement
• Calculated creatinine clearance >30 mL/min (as calculated by the Cockcroft-Gault formula)
• Patients with PT/INR or aPTT ≤2xULN.
• ECOG performance status ≤ 2 unless related to CLL.
• Male or female ≥ 18 years of age.
• Ability to swallow and retain oral medication.
• Woman of childbearing potential (WOCBP) who are sexually active must use highly effective methods of contraception during treatment and for 2 days after the last dose of acalabrutinib and for 12 months following last dose of rituximab. (see Appendix 3 for examples)
• Willingness and ability to comply with study and follow-up procedures, and give written informed consent.

Exclusion Criteria

• 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.

• 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.
• Known history of HIV.
• Known histological transformation from CLL to an aggressive lymphoma.
• 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.
• Live virus vaccines within 4 weeks prior to C1D1 or during rituximab therapy.
• History of anaphylaxis (excluding infusion related reactions) in association with previous anti-CD20 administration or acalabrutinib.
• Any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
• Symptomatic, or history of documented congestive heart failure (NY Heart Association functional classification III-IV)
• Uncontrolled cardiac arrhythmia (Patients with controlled atrial fibrillation/flutter are eligible)
• Myocardial infarction within 3 months of enrollment
• Angina not well-controlled by medication
• Poorly controlled or clinically significant atherosclerotic vascular disease including cerebrovascular accident (CVA), transient ischemic attack (TIA), angioplasty, cardiac/vascular stent