A Study of Different Doses of Ibrutinib in Participants With Chronic Lymphocytic Leukemia (CLL)

Study Drug Administration:

Each study cycle is 28 days.

If you are found to be eligible to take part in this study, you will take ibrutinib capsules
by mouth every day for 3 cycles. Each dose of ibrutinib should be taken at about the same
time, either with or without food.

During Cycle 1, you will receive the highest dose of ibrutinib (the dose that is currently
FDA approved). You will take 3 capsules each day during Cycle 1. During Cycle 2, you will
receive the second-highest dose and you will take 2 capsules each day. During Cycle 3, you
will take the lowest dose of ibrutinib and you will take 1 capsule each day.

You must swallow the ibrutinib capsules whole without opening, breaking, or chewing them.

You will be given a study drug diary to keep track of each dose of ibrutinib taken, including
the time the dose was taken, any missed or vomited doses and the reason for missing the dose,
and any doses that you vomited.

Study Visits:

On Days 1, 8 and 28 of each cycle blood (about 1-2 tablespoons total) will be drawn before
your dose of ibrutinib and then at 4 and 24 hours after your dose for pharmacodynamic (PD)
and pharmacokinetic (PK) testing, to help researchers understand how ibrutinib works in the
body, and to learn if the dose you are taking is as effective as other doses (Exception:
there will be no 4-hour blood draw on day 28). PK testing measures the amount of study drug
in the body at different time points. PD testing measures how the level of study drug in your
body may affect the disease. You will need to return to the clinic on the following day (Days
2, 9 and 29 of each cycle [Day 1 of the next cycle]) for the last blood draw.

On Day 28 of each cycle:

- You will have a physical exam

- Blood (about 1-2 tablespoons) will be drawn for routine tests.

- You will have an EKG.

Length of Study:

You may receive ibrutinib on this study for up to 3 cycles. After this time, you will
continue treatment for CLL as directed by your doctor. This may or may not include ibrutinib.
If you do continue to take ibrutinib after the study is over, your doctor will determine the
best dose for you to be taking.

You will no longer be able to take the study drug if the disease gets worse, if intolerable
side effects occur, or if you are unable to follow study directions.

Your participation in this study will be over after your last dose of ibrutinib (after the
end of Cycle 3).

This is an investigational study. Ibrutinib is FDA approved and commercially available for
the treatment of CLL. It is considered investigational to compare 3 different doses of
ibrutinib. The study doctor can explain how the study drug is designed to work.

Up to 12 participants will be enrolled in this study. All will take part at MD Anderson.

Inclusion Criteria:

1. Patients with a diagnosis of CLL (any stage) with ALC >/= 20 x 109/l, requiring
therapy.

2. Able to receive ibrutinib through commercial supply, i.e., insured patients meeting
FDA-approved indications.

3. Age >/=18 years.

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

5. Adequate end organ function, defined as the following: total bilirubin limit of normal (ULN, unless due to Gilbert syndrome, in which case it should be 3.0 x ULN), ALT and AST /= 25 ml/min.

6. Able to understand and sign the IRB-approved informed consent document for this trial.

7. Women of childbearing potential (WOCBP) must practice 2 effective methods of birth
control during the course of the study. Male patients who are partners of WOCBP should
also practice an effective method of contraception. Effective methods of birth control
include diaphragm or condoms with spermicidal foam or jelly, birth control pills
(BCPs), injections or patches, intra-uterine devices (IUDs) and surgical
sterilization. Postmenopausal women must be amenorrheic for >/= 12 months to be
considered of non-childbearing potential, Women and men must continue birth control
for the duration of the trial and >/= 3 months after the last dose of study drug, All
WOCBP MUST have a negative pregnancy test prior to beginning ibrutinib on study.

8. Patients should have discontinued any and all other therapy for CLL >/= 48 hours prior
to start of study therapy and recovered from any toxicity due to these therapies to
grade
Exclusion Criteria:

1. Previous treatment with ibrutinib.

2. Current therapy with warfarin or other anticoagulants at therapeutic doses, e.g., low
molecular weight heparin, fondaparinux, dabigatran, rivaroxaban, apixaban or edoxaban
that are unable to be discontinued.

3. Active gastrointestinal conditions that are expected to impair absorption of orally
administered medications.

4. Active, uncontrolled infection.

5. History of hypersensitivity to ibrutinib.

6. Pregnancy or lactation.

7. Patients with leukemic involvement of the central nervous system.

8. Patients who currently have or have a history of the following within 6 months
preceding study entry are not eligible: Unstable angina (UA) or myocardial infarction
(MI), Clinically significant atrial or ventricular arrhythmias (e.g., AF, atrial
flutter, ventricular tachycardia, ventricular fibrillation, or torsades de pointes),
New York Heart Association (NYHA) class III or IV heart failure.

9. Patients on strong CYP3A inducers or inhibitors that are unable to be discontinued.
The list of drugs that interact with cytochrome P450 enzymes can be found online at:
http://medicine.iupui.edu/clinpharm/DDIs/ClinicalTable.aspx