| Eligibility |
Inclusion Criteria:
- Confirmed diagnosis of MCL with CD20 and cyclin D1 positivity or cyclin D1 negative
MCL classic histology in tissue biopsy. Patients must have never received any prior
therapy for their disease. Patients have been observed for 3 - 6 months with no
progression as per imaging assessments
- High risk smoldering MCL (i.e. patients without any B symptoms or any symptoms related
to MCL warranting immediate systemic therapy) with at least one or more of these
eligibility criteria:
- Ki-67 of 15-30% (Ki-67% from involved tissue not bone marrow [BM], unless
confirmed by pathologist),
- White blood cells (WBC) 15-30k
- Lymph node size 3-5 cm in diameter
- Complex karyotype
- TP53 mutated or wild type and/or del17p (fluorescence in situ hybridization
[FISH]% 10-50%)
- MYC positive MCL. MYC positive (either by FISH or by immunohistochemistry [IHC]
and confirmed by pathology at MD Anderson Cancer Center [MDACC])
- Presence of either or KMT2D, BIRC3, NOTCH2, NSD2 or more than one mutation in the
initial next generation sequencing (NGS) panel testing are allowed
- Understand and voluntarily sign an institutional review board (IRB)-approved informed
consent form
- Age >= 18 years at the time of signing the informed consent
- Patients should in general have bi-dimensional measurable disease with their biggest
tumor less than or equal to 5 cm. (Bone marrow or gastrointestinal [GI] only
involvement is acceptable)
- Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
- Cardiology clearance is required. Discussion with cardiologist and co-principal
investigator (PI) is required before starting ibrutinib
- With minimal disease or absent disease related symptoms but anxious to start systemic
therapy
- Absence of cytopenia attributed to bone marrow (BM) infiltration
- Absolute neutrophil count (ANC) > 1000/mm^3
- Platelet count > 100,000/mm^3
- Patients who have bone marrow infiltration by MCL are eligible if their ANC is >= than
500 or their platelet level is >= than 50,000 /mm^3. Platelet transfusions are allowed
- Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and
alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) < 3 x upper
limit of normal or < 5 x upper limit of normal if hepatic metastases are present
- Serum bilirubin < 1.5 mg/dl
- Creatinine (Cr) clearance >= 30 mL/min
- Disease free of prior malignancies for equal to or greater than 6 months 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. Patients must be willing to receive
transfusions of blood products
- Willing and able to participate in all study related procedures and therapy including
swallowing capsules without difficulty and having a screening core biopsy
- Female subjects who are of non-reproductive potential (i.e., post-menopausal by
history - no menses for >= 1 year; OR history of hysterectomy; OR history of bilateral
tubal ligation; OR history of bilateral oophorectomy). Female subjects of childbearing
potential must have a negative serum pregnancy test upon study entry
- Male and female subjects who agree to use highly effective methods of birth control
(e.g., implants, injectable, combined oral contraceptives, some intrauterine devices
[IUDs], sexual abstinence, or sterilized partner) and a barrier method (e.g., condoms,
vaginal ring, sponge, etc) during the period of therapy and for 30 days after the last
dose of study drug for females and 90 days for males
Exclusion Criteria:
- Any serious medical condition including but not limited to uncontrolled hypertension,
arrhythmias, diabetes mellitus, active/symptomatic coronary artery disease, chronic
obstructive pulmonary disease (COPD), renal failure, very painful, intolerable
symptoms from splenomegaly, leukemic features, active hemorrhage, or psychiatric
illness that, in the investigator's opinion, places the patient at unacceptable risk
and would prevent the subject from signing the informed consent form
- Patients with ANY of the following risk factors:
- Clinically significant disease related symptoms (including significant B
symptoms) compromising the performance status to more than 1
- Blastoid variant histology
- Pleomorphic variant histology
- Ki-67 > 30%
- Bulky tumors > 5 cm
- Central nervous system (CNS) involvement at diagnosis
- All patients must not have received any prior treatment for mantle cell lymphoma
- Prior exposure to BTK inhibitor
- Pregnant or breastfeeding females
- Known history of human immunodeficiency virus (HIV) or active with hepatitis C virus
(HCV) or hepatitis B virus (HBV). Subjects who are positive for hepatitis B core
antibody, hepatitis B surface antigen, or hepatitis C antibody must have a negative
polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive
will be excluded
- All patients with history of central nervous system lymphoma
- History of stroke or intracranial hemorrhage within 6 months prior to signing the
consent
- Currently active, or past history/of clinically significant cardiovascular disease
such as uncontrolled arrhythmia or any Class 3 or 4 congestive heart failure as
defined by the New York Heart Association Classification, or even controlled
arrhythmias (any grade) on medications or a history of myocardial infarction, unstable
angina, or acute coronary syndrome within 6 months prior to randomization
- Patients with prior history of atrial fibrillation or any type of cardiac arrhythmias
and/or who underwent ablation and are in normal sinus rhythm (exceptions include
patients who are asymptomatic and those who are given cardiology clearance)
- Unable to swallow capsules, 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.
- Requires concomitant anticoagulation with warfarin or equivalent vitamin K antagonist,
active treatment for pulmonary embolism (PE)/ deep vein thrombosis (DVT) and persons
with mechanical cardiac valves
- Subject who received a strong cytochrome P450 (CYP) 3A inhibitor within 7 days prior
to the first dose of ibrutinib or subject who requires continuous treatment with a
strong CYP3A inhibitor
- Subjects with chronic liver disease and hepatic impairment meeting Child-Pugh class C
- Any uncontrolled active systemic infection
- Major surgery within 4 weeks of first dose of study drug
- Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug
- Recent infection requiring systemic treatment that was completed =< 14 days before the
first dose of study drug
- Known bleeding disorders (e.g., von Willebrand's disease or hemophilia)
- Unresolved toxicities from prior anticancer therapy, defined as having not resolved to
Common Terminology Criteria for Adverse Event (CTCAE, version [v] 4.0), grade =< 1, or
to the levels dictated in the inclusion/exclusion criteria with the exception of
alopecia
- Concurrent systemic immunosuppressant therapy within 21 days of the first dose of
study drug
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