| Eligibility |
Inclusion Criteria:
- Previously untreated, histologically confirmed follicular lymphoma, World Health
Organization (WHO) classification grade I, II, or IIIa (> 15 centroblasts per high
power field with centrocytes present) that is stage III, IV, or bulky (i.e., single
mass >= 7 cm in any unidimensional measurement) stage II and requires therapy at the
discretion of the primary physician
- Bone marrow biopsies as the sole means of diagnosis are not acceptable, but they
may be submitted in conjunction with nodal biopsies; fine needle aspirates are
not acceptable for diagnosis
- Failure to submit pathology specimens within 60 days of patient registration will
be considered a major protocol violation
- Institutional flow cytometry or immunohistochemistry must confirm cluster of
differentiation 20 (CD20) antigen expression
- All risk by follicular lymphoma international prognostic index (FLIPI): 0-5 risk
factors
- No prior systemic therapy for non-Hodgkin lymphoma (NHL) including chemotherapy or
immunotherapy (e.g., monoclonal antibody-based therapy), radiation therapy, or
radioimmunotherapy
- For non-NHL conditions, no chemotherapy, radiotherapy, or major surgery within 4 weeks
(6 weeks for nitrosoureas or mitomycin C) of enrollment; no patients who have ongoing
adverse events from agents administered more than 4 weeks previously
- No prior exposure to any of the study agents
- No corticosteroids within two weeks prior to study entry, except for maintenance
therapy for a non-malignant disease; dose of corticosteroid or prednisone (or its
equivalent) should not exceed 20 mg per day; corticosteroid premedication for
rituximab is allowed
- Eastern Cooperative Oncology Group (ECOG) performance status must be =< 2
- Measurable disease must be present either on physical examination or imaging studies;
non-measurable disease alone is not acceptable; any tumor mass > 1 cm is acceptable;
lesions that are considered non-measurable include the following:
- Bone lesions (lesions if present should be noted)
- Ascites
- Pleural/pericardial effusion
- Lymphangitis cutis/pulmonis
- Bone marrow (involvement by NHL should be noted)
- Patients with human immunodeficiency virus (HIV) infection are eligible, provided they
meet the following:
- No evidence of coinfection with hepatitis B or C
- CD4+ cell count >= 400/mm^3
- No evidence of resistant strains of HIV
- If not on anti-HIV therapy, HIV viral load < 10,000 copies HIV ribonucleic acid
(RNA)/mL
- If on anti-HIV therapy, HIV viral load < 50 copies HIV RNA/mL
- No history of acquired immunodeficiency syndrome (AIDS)-defining conditions
- No use of strong cytochrome P450, family 3, subfamily A, polypeptide 4/5
(CYP3A4/5) inhibitors or inducers
- No known central nervous system (CNS) involvement by lymphoma
- No treatment with strong inhibitors or inducers of CYP3A4/5
- No evidence of active hepatitis B or C infections (i.e., no positive serology for
anti-hepatitis B virus [HBV] or anti-hepatitis C virus [HCV] antibodies); HBV
seropositive patients (hepatitis B surface antigen [HBsAg] +) are eligible if they are
closely monitored for evidence of active HBV infection by HBV deoxyribonucleic acid
(DNA) testing and receive suppressive therapy with lamivudine or other HBV suppressive
therapy until 6 months after the last rituximab dose
- No history of erythema multiforme, toxic epidermal necrolysis or Stevens-Johnson
syndrome
- No history of uncontrolled seizures
- No autoimmune disorder that requires active immunosuppression
- No intracranial hemorrhage within the last 6 months
- Patients must be non-pregnant and non-nursing; females of childbearing potential
(FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at
least 25 mIU/mL within 10-14 days and again within 24 hours prior to starting cycle 1
of lenalidomide; further, they must either commit to continued abstinence from
heterosexual intercourse or begin TWO acceptable methods of birth control: one highly
effective method and one additional effective method AT THE SAME TIME, at least 28
days before starting lenalidomide; FCBP must also agree to ongoing pregnancy testing;
men must agree to use a latex condom during sexual contact with a FCBP, even if they
have had a successful vasectomy; a FCBP is a sexually mature woman who: 1) has not
undergone a hysterectomy or bilateral oophorectomy, or 2) has not been naturally
postmenopausal for at least 24 consecutive months (i.e., has had menses at any time
preceding 24 consecutive months); all patients must be counseled by a trained
counselor every 28 days about pregnancy precautions and risks of fetal exposure
- No known human anti-chimeric antibody (HACA) positivity
- No anticoagulation with warfarin is allowed; patients must not have received warfarin
within 28 days prior to registration; alternative anticoagulant may be used
- Patients must not be receiving concurrent treatment with other investigational drugs
- Patients must not have a history of allergic reactions attributed to compounds of
similar chemical or biologic composition to lenalidomide, ibrutinib, or other agents
used in study
- Patients must not have presence of transfusion-dependent thrombocytopenia
- No currently active clinically significant cardiovascular disease including the
following:
- No uncontrolled arrhythmia
- No congestive heart failure
- No class 3 or 4 cardiac disease as defined by the New York Heart Association
Functional Classification
- No history of myocardial infarction, deep venous or arterial thrombosis within 6
months prior to registration
- No prior malignancy with the exceptions listed below:
- Malignancy treated with curative intent and with no evidence of active disease
for more than 3 years prior to screening and felt to be at low risk for
recurrence by the treating physician
- Adequately treated non-melanomatous skin cancer or lentigo maligna melanoma
without current evidence of disease
- Adequately treated cervical carcinoma in situ without current evidence of disease
- Patients must be >= 18 years of age
- Absolute neutrophil count (ANC) >= 1,000/microliter (should be present independent of
growth factor or transfusion support for at least 7 days prior to first dose of study
drug)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper
limit of normal (ULN) (should be present independent of growth factor or transfusion
support for at least 7 days prior to first dose of study drug)
- Total bilirubin =< 1.5 x ULN unless attributable to Gilbert's syndrome (should be
present independent of growth factor or transfusion support for at least 7 days prior
to first dose of study drug)
- Creatinine clearance > 60 mL/min (patients on dialysis are not eligible); to be
calculated by method of Cockcroft-Gault, using actual weight (should be present
independent of growth factor or transfusion support for at least 7 days prior to first
dose of study drug)
- Creatinine =< 2 x ULN (should be present independent of growth factor or transfusion
support for at least 7 days prior to first dose of study drug)
- Platelet count >= 75,000/microliter (should be present independent of growth factor or
transfusion support for at least 7 days prior to first dose of study drug)
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