| Eligibility |
Inclusion Criteria:
- Confirmed diagnosis of mantle cell lymphoma with CD20 positivity in tissue biopsy
- MCL patients must have a clinical indication to start systemic therapy. Symptoms and
features of MCL include any of the following: a) B-symptoms, b) Mantle Cell Lymphoma
International Prognostic Index (MIPI) > 3, c) Ki 67 >= 30%, d) bulky tumors > 10 cm or
in case of >= 2 tumors, each >= 5 cm in diameter, e) disease threatening organ
function, f) elevated lactate dehydrogenase (LDH), g) peripheral blood (PB) white
blood cell (WBC) > 50,000, h) pancytopenia due to bone marrow MCL, i) patient's choice
due to anxiety; j) pain due to lymphoma; k) somatic mutations in the TP53, NSD2 or
NOTCH genes; l) size of spleen >= 20 cm
- Newly diagnosed MCL with no prior therapy
- Sign (or their legally-acceptable representatives must sign) an informed consent
document indicating that they understand the purpose of and procedures required for
the study, including biomarkers, and are willing to participate in the study
- Bi-dimensional measurable disease using both computed tomography (CT) scan and/or
positron emission tomography (PET)-CT or gastrointestinal biopsies, CT
gastrointestinal, bone marrow or spleen only patients are allowable
- Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
- Absolute neutrophil count (ANC) >= 1000/mm^3 independent of growth factor support
- Platelets >= 100,000/mm^3 or >= 50,000/mm^3 if bone marrow involvement without
necessitating transfusion
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x upper limit
of normal (ULN)
- Total bilirubin =< 1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome or of
non-hepatic origin
- Creatinine clearance (CLcr) > 50 mL/min
- Cardiac ejection fraction >= 50% by echocardiogram (ECHO) or multigated acquisition
(MUGA)
- Disease free of prior malignancies with exception of currently treated basal cell,
squamous cell carcinoma of the skin, carcinoma "in situ" of the cervix or breast, or
other malignancies in remission (including prostate cancer patients in remission from
radiation therapy, surgery or brachytherapy), not actively being treated with life
expectancy of greater than 3 years. Principal investigator (PI) can use clinical
judgement in the best interest of patients
- Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
test (within 28 days of initiation of protocol therapy) and must be willing to use
acceptable methods of birth control during and after the study consistent with local
regulations regarding the use of birth control methods for subjects participating in
clinical trials. Men must agree to use a latex condom during sexual contact with a
female of childbearing potential even if they have had a successful vasectomy. Men
must agree to not donate sperm during and after the study. For females, these
restrictions apply for 1 month after the last dose of study drug. For males, these
restrictions apply for 3 months after the last dose of study drug
- A female of childbearing potential 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 in the preceding 24 consecutive months).
Exclusion Criteria:
- Any serious medical condition including but not limited to, uncontrolled hypertension,
uncontrolled diabetes mellitus, active/symptomatic coronary artery disease, chronic
obstructive pulmonary disease (COPD), renal failure, active hemorrhage, laboratory
abnormality, or psychiatric illness that, in the investigators opinion, places the
patient at unacceptable risk or would prevent the subject from signing the informed
consent form
- Pregnant or breast-feeding females
- Known human immunodeficiency virus (HIV) infection (HIV testing is not required)
- Evidence of other clinically significant uncontrolled condition(s) including, but not
limited to:
- Uncontrolled and/or active systemic infection (viral, bacterial or fungal)
- Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note:
subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B
surface [HBs] antigen negative-, anti-HBs antibody positive and anti-hepatitis B
core [HBc] antibody negative) or positive anti-HBc antibody from intravenous
immunoglobulins (IVIG) may participate
- Treatment with any of the following within 7 days prior to the first dose of study
drug:
- Steroid therapy for anti-neoplastic intent
- Moderate or strong cytochrome P450 3A (CYP3A) inhibitors
- Moderate or strong CYP3A inducers
- Administration or consumption of any of the following within 3 days prior to the first
dose of study drug:
- Grapefruit or grapefruit products
- Seville oranges (including marmalade containing Seville oranges)
- Star fruit
- Patients with active hepatitis B infection (not including patients with prior
hepatitis B vaccination; or positive serum hepatitis B antibody). Known hepatitis C
infection is allowed as long as there is no active disease and is cleared by
gastrointestinal (GI) consultation
- Central nervous system with mantle cell lymphoma
- Significant neuropathy (grades 3 to 4, or grade 2 with pain) within 14 days prior to
enrollment
- Contraindication to any of the required concomitant drugs or supportive treatments or
intolerance to hydration due to preexisting pulmonary or cardiac impairment including
pleural effusion requiring thoracentesis or ascites requiring paracentesis unless due
to lymphoma
- Malabsorption syndrome, disease significantly affecting gastrointestinal function, or
resection of the stomach or small bowel or ulcerative colitis, symptomatic
inflammatory bowel disease, or partial or complete bowel obstruction, or any other
gastrointestinal condition that could interfere with the absorption and metabolism of
ibrutinib
- Major surgery within 4 weeks of initiation of therapy or a wound that has not fully
healed within 4 weeks of randomization. Clearance letter from primary physician
required
- Requires anticoagulation with warfarin or equivalent vitamin K antagonist
- Requires chronic treatment with strong CYP3A inhibitors
- Patients with New York Health Association (NYHA) Class III and IV heart failure,
myocardial infarction in the preceding 6 months, and significant conduction
abnormalities, including but not limited to left bundle branch block, 2nd degree
atrioventricular (AV) block type II, 3rd degree block, QT prolongation (corrected QT
[QTc] > 500 msec), sick sinus syndrome, ventricular tachycardia, symptomatic
bradycardia (heart rate < 50 bpm), hypotension, light headedness and syncope,
persistent and uncontrolled atrial fibrillation
- Recent placement of a stent and by recommendation of their cardiologist need to stay
on anticoagulants such as warfarin or equivalent vitamin K antagonist
- Acute infection requiring treatment (IV antibiotics, antivirals, or antifungals)
within 14 days prior to initiation of therapy
- Child-Pugh class B or C are excluded
- Vaccinated with live, attenuated vaccines within 4 weeks of randomization
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