Ibrutinib and Rituximab Compared With Fludarabine Phosphate, Cyclophosphamide, and Rituximab in Treating Patients With Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Inclusion Criteria:

Diagnosis of CLL according to the National Cancer Institute (NCI)/Internal Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria or small lymphocytic lymphoma (SLL) according to the World Health Organization (WHO) criteria; this includes previous documentation of:

Biopsy-proven small lymphocytic lymphoma or

Diagnosis of CLL according to the NCI/IWCLL criteria as evidenced by all of the following:

Peripheral blood lymphocyte count of greater than 5 x 10^9/L

Immunophenotype consistent with CLL defined as:

The predominant population of lymphocytes share both B-cell antigens (cluster of differentiation [CD]19, CD20 [typically dim expression], or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc)
Clonality as evidenced by kappa or lambda light chain restriction (typically dim immunoglobulin expression)
Negative FISH analysis for t(11;14)(immunoglobulin heavy locus [IgH]/cyclin D1 [CCND1]) on peripheral blood or tissue biopsy (e.g. marrow aspirate) or negative immunohistochemical stains for cyclin D1 staining on involved tissue biopsy (e.g. marrow aspirate or lymph node biopsy)
No prior chemotherapy, Bruton's tyrosine kinase (BTK) inhibitor therapy, or monoclonal anti-body therapy for treatment of CLL or SLL

Has met at least one of the following indications for treatment:

Evidence of progressive marrow failure as manifested by the development of worsening anemia (hemoglobin [Hg] < 11 g/dl) and/or thrombocytopenia (platelets < 100 x 10^9/L)
Symptomatic or progressive lymphadenopathy, splenomegaly, or hepatomegaly

One or more of the following disease-related symptoms:

Weight loss >= 10% within the previous 6 months
Grade 2 or 3 fatigue attributed to CLL
Fevers > 100.5 Fahrenheit (F) for 2 weeks without evidence of infection
Clinically significant night sweats without evidence of infection
Progressive lymphocytosis (not due to the effects of corticosteroids) with an increase of > 50% over a two-month period or an anticipated doubling time of less than six months
ECOG performance status between 0-2
Life expectancy of >= 12 months
Ability to tolerate FCR based therapy
No deletion of 17p13 on cytogenetic analysis by FISH
Glomerular filtration rate (GFR) > 40 mL/minute as calculated by the Cockcroft-Gault formula (obtained =< 14 days prior to registration)

Total bilirubin =< 2.5 x upper limit of normal (ULN) (obtained =< 14 days prior to registration) unless due to Gilbert's disease; for those with a total bilirubin > 2.5 x ULN, a direct bilirubin should be performed and must be < 1.5 mg/dL for Gilbert's to be diagnosed

If value is higher due to hepatic involvement by CLL, patient is eligible

Serum glutamic oxaloacetic transaminase (SGOT) (aspartate transaminase [AST])/serum glutamate-pyruvate transaminase (SGPT) (alanine transaminase [ALT]) =< 3.0 x the institutional ULN (obtained =< 14 days prior to registration)

If value is higher due to hepatic involvement by CLL, patient is eligible

Prothrombin time (PT)/international normalized ratio (INR) < 1.5 ULN and partial thromboplastin time (PTT) (activated partial thromboplastin time [aPTT]) < 1.5 X ULN (obtained =< 14 days prior to registration)

If value is higher due to hepatic involvement by CLL, patient is eligible
No active hemolytic anemia requiring immunosuppressive therapy or other pharmacologic treatment; patients who have a positive Coombs test but no evidence of hemolysis are NOT excluded from participation
No current use of corticosteroids; EXCEPTION: low doses of steroids (< 10 mg of prednisone or equivalent dose of other steroid) used for treatment of non-hematologic medical condition (e.g. chronic adrenal insufficiency) is permitted
No previous use of corticosteroids for autoimmune complications that have developed since the initial diagnosis of CLL; prior use of corticosteroids for reasons other than treatment of autoimmune complications is allowed
No other active primary malignancy (other than non-melanomatous skin cancer or carcinoma in situ of the cervix) requiring treatment or limiting expected survival to =< 2 years; NOTE: if there is a history of prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy for their cancer)
Able to adhere to the study visit schedule and other protocol requirements
No major surgery within the last 4 weeks (28 days) of first dose of study drug or minor surgery within 3 days of first dose of study drug
No radiation therapy =< 4 weeks prior to registration

Patients with human immunodeficiency virus (HIV) infection may be eligible provided they meet the following criteria:

CD4-positive cell count >= lower limit of institutional normal
HIV viral load < 10,000 copies HIV ribonucleic acid (RNA)/mL (if not on anti-HIV therapy) OR < 50 copies HIV RNA/mL (if on anti-HIV therapy)
No evidence of hepatitis B or C infection
No evidence of resistant strains of HIV
No history of acquired immune deficiency syndrome (AIDS)-defining condition

Patients must not have any of the following conditions:

Congestive heart failure or New York Heart Association Functional Classification III or IV congestive heart failure
History of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to registration
Recent infections requiring systemic treatment; need to have completed anti-biotic therapy > 14 days before the first dose of study drug
Cerebral vascular accident or intracranial bleed within the last 6 months
Infection with known chronic, active hepatitis C
Serologic status reflecting active hepatitis B or C infection; patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment (PCR positive patients will be excluded)
Patients are not eligible if they require treatment with a strong cytochrome P450 (CYP) family 3, subfamily A (3A) inhibitor
Patients may not be on any other investigational agents
Patients may not have received warfarin or another vitamin K antagonist in the preceding 30 days
Women must not be pregnant or breast-feeding since this study involves an investigational agent whose genotoxic, mutagenic, and teratogenic effects on the developing fetus and newborn are unknown; female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to registration to rule out pregnancy; female patients who are of non-reproductive potential are those who are post-menopausal by history (i.e. no menses for >= 1 year); OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy)
Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception or to abstain from sexual intercourse for 90 days after the last dose of study drug

Patient must be able to swallow capsules and not have the following conditions:

Disease significantly affecting gastrointestinal function
Resection of the stomach or small bowel
Symptomatic inflammatory bowel disease
Ulcerative colitis
Partial or complete bowel obstruction
Patient must not be on any other systemic immunosuppressant therapy other than corticosteroids within 28 days of the first dose of study drug
Patient must not be vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug
Patient must not have any known bleeding disorders (e.g., von Willebrand's disease) or hemophilia
Patient must not have currently active, clinically significant hepatic impairment (>= moderate hepatic impairment according to the NCI/Child Pugh)