Ibrutinib in Newly Diagnosed Mantle Cell Lymphoma With Low-Risk Disease

Study Drug Administration:

Each study cycle is 28 days.

If participant is found to be eligible to take part in this study, participant will take
ibrutinib by mouth 1 time per day at the same time every day with 1 cup (about 8 ounces) of
water.

If participant misses a dose, participant can take it up to 6 hours after the time
participant would have taken it. If it is later than 6 hours, participant should skip the
dose and take participant's next dose at participant's usual time the next day.

Participant should return any unused study drug to all study visits.

Study Visits:

On Days 1, 8, 15, and 22 of Cycle 1, participant's vital signs will be taken.

On Day 1 of every cycle:

- Participant will have a physical exam.

- Blood (about 2 teaspoons) will be drawn for routine tests. If participant can become
pregnant, this blood will also be used for a pregnancy test.

- Blood (about 2 teaspoons) will be drawn for biomarker testing. (Cycles 3 and 7 only)

On Day 1 of Cycle 3 and Cycle 7:

- Blood (about 2 teaspoons) will be drawn for biomarker testing.

- Participant will have a bone marrow biopsy and aspirate for biomarker testing.

Every other cycle starting in Cycle 3 and up to Cycle 8 (Cycles 3, 5, and 7) and then every 4
cycles after that starting in Cycle 9 (Cycles 9, 13, 17, and 21), participant will have a CT
scan to check the status of the disease.

At any time your doctor thinks it is needed, participant may have any of the following
procedures to check the status of the disease:

- PET/CT scan

- bone marrow biopsy

- colonoscopy/GI endoscopy with a core biopsy

If participant can become pregnant, and the doctor thinks it is needed, blood (about 1
teaspoon) or urine will be collected for a pregnancy test at any time while participant is on
study.

Length of Study:

Participant may continue taking the study drug for up to 3 years. Participant will no longer
be able to take the study drug if the disease gets worse, if intolerable side effects occur,
or if participant is unable to follow study directions.

Participation on the study will be over after the last follow-up phone call.

End-of-Treatment Visit:

Within 30 days after participant's last dose of the study drug:

- Participant will have a physical exam.

- Participant will have an EKG.

- Blood (about 2 teaspoons) will be drawn for routine tests and to check the status of the
disease. If participant is able to become pregnant, this blood sample will also be used
for a pregnancy test.

- Participant will have a PET/CT scan and chest x-ray to check the status of the disease.

- If the doctor thinks it is needed, participant may have an endoscopy with a biopsy; a
colonoscopy with a biopsy; and/or a bone marrow biopsy.

Long Term Follow Up Period:

Every 2 months for the first 6 months after the End-of-Treatment visit, then every 2-4 months
for 2 years, and then 4-6 months after 2 years, a member of the study staff will call
participant to ask about participant's health. These phone calls will take about 5 minutes
each time.

Participant's study data and results may be used by Pharmacyclics, its affiliates and its
collaborators (such as Janssen Biotech, Inc.) for research related to cancer.

This is an investigational study. Ibrutinib is FDA approved and commercially available for
the treatment of several types of cancer. Its use in treating MCL is investigational. The
study doctor can explain how the study drug is designed to work.

Up to 30 participants will be enrolled in this study. All will take part at MD Anderson.

Inclusion Criteria:

1. Confirmed diagnosis of MCL with CD20 and cyclin D1 positivity 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.

2. Low risk disease (without the following risk factors: Blastoid variant histology,
Pleomorphic variant histology, Ki-67 >/= 50%, High-risk MCL International Prognostic
Index (MIPI), Bulky tumors >3 cm, Presence of B symptoms)

3. Understand and voluntarily sign an institutional review board (IRB)-approved informed
consent form.

4. Age >/= 18 years at the time of signing the informed consent.

5. Patients should in general have bi-dimensional measurable disease with their biggest
tumor less than or equal to 3 cm. [bone marrow or gastrointestinal (GI) only
involvement is acceptable].

6. Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less

7. 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.

8. 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 and creatinine (Cr) Clearance >/= 30 mL/min.

9. Disease free of prior malignancies of 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.

10. Willing and able to participate in all study related procedures and therapy including
swallowing capsules without difficulty and having a screening core biopsy.

11. Female subjects who are of non-reproductive potential (ie, 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.

12. Male and female subjects who agree to use highly effective methods of birth control
(eg, implants, injectables, combined oral contraceptives, some intrauterine devices
[IUDs], sexual abstinence, or sterilized partner) and a barrier method (eg., 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:

1. Any serious medical condition including but not limited to uncontrolled hypertension,
diabetes mellitus, active/symptomatic coronary artery disease, chronic obstructive
pulmonary disease (COPD), renal failure, 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.

2. Pregnant or breastfeeding females.

3. 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.

4. All patients with history of central nervous system lymphoma.

5. History of stroke or intracranial hemorrhage within 6 months prior to signing the
consent.

6. Clinically significant cardiovascular disease such as uncontrolled or symptomatic
arrhythmias, congestive heart failure or myocardial infarction within 6 months at the
time of consent or any Class 3 (moderate) or 4 (severe) cardiac disease defined by the
New York Heart Association Classification.

7. Significant screening electrocardiogram (ECG) abnormalities including left bundle
branch block, 2nd degree atrioventricular (AV) block type II, 3rd degree block,
bradycardia (< 50bpm), or QTc >500 msec.

8. 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.

9. 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.

10. Requires treatment with strong CYP3A4/5 inhibitors.
http://medicine.iupui.edu/clinpharm/ddis/table.aspx

11. Patients with blastoid and pleomorphic variants.

12. Ki-67 to be equal or more than 50%.

13. Patients with bi-dimensional measurable disease with a tumor >/= 3 cm.

14. Currently active, clinically significant hepatic impairment Child-Pugh class B or C
according to the Child Pugh classification

15. Any uncontrolled active systemic infection

16. Major surgery within 4 weeks of first dose of study drug.

17. Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.

18. Recent infection requiring systemic treatment that was completed the first dose of study drug.

19. Known bleeding disorders (eg, von Willebrand's disease or hemophilia).