Administration of Jakafi (Ruxolitinib) to Patients With Previously Untreated High-Risk Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

If you agree to take part in this study, you will take ruxolitinib pills by mouth 2 times
each day. The study doctor will tell you which dose you are taking.

Length of Study Participation:

You may receive ruxolitinib for up to 3 years. If the study doctor thinks it is in your best
interest, you may be able to continue receiving ruxolitinib after 3 years. This will be
discussed with you. 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 the follow-up visit (described below).

Study Visits:

All study visits during screening and the first 8 months of participation (except the Month 2
visit) will take place at MD Anderson. For the Month 2 visit and every other visit after
Month 8, if it is more convenient for you, you may have your physical exams and routine blood
draws completed at a local lab or doctor's office. The results of the tests/procedures will
be sent to the study doctor for review. This option will be discussed with you. If you choose
all visits will take place at MD Anderson, you will be seen at least every 4 months.

Before you start taking ruxolitinib:

- Blood (about 2 teaspoons) will be drawn for cytokine testing and for a special kind of
testing that tells researchers if there are changes in the pathways that helps CLL/SLL
cells grow. This is called B-cell receptor testing. Cytokines are proteins that may
affect the immune system.

- Blood (2 teaspoons) will be drawn for routine tests.

- You will have a Whole Body CT scan to check the status of the disease.

- You will have a Bone Marrow biopsy and aspiration to check the status of the disease. To
collect a bone marrow aspirate, an area of the hip or other site is numbed with a
anesthetic, and a small amount of bone marrow is withdrawn through a large needle.

- If you can become pregnant, blood (about 1 teaspoon) and/or urine will be collected for
a pregnancy test.

On Days 1 and Day 15 (+/- 7 days), Month 3, Month 6, every 2 months (Months 8 10, and so on).
as well as every time you come to MD Anderson as part of your routine care:

- You will have a physical exam.

- Blood (2 teaspoons) will be drawn for routine tests. If needed, this blood draw may be
repeated every 2-4 weeks.

- You will complete 2 questionnaires about your symptoms. This should take about 10
minutes to complete.

At about Month 2, Month 10, and every 4 months after that (Month 14,18, and so on), if
performed by your local doctor as part of your routine care:

- You will have a physical exam.

- Blood (2 teaspoons) will be drawn for routine tests. If needed, this blood draw may be
repeated every 2-4 weeks.

About 3 months after you start treatment, in addition to the testing listed above, blood (2
teaspoons) will be drawn for cytokine testing and for B-cell receptor testing.

About 6 months after you start treatment in addition to the tests above:

- Blood (2 teaspoons) will be drawn for cytokine testing and for B-cell receptor testing.

- You will have a bone marrow aspiration to check the status of the disease. To collect a
bone marrow aspirate, an area of the hip or other site is numbed with anesthetic, and a
small amount of bone marrow is withdrawn through a large needle.

- You will have a whole body CT scan.

Follow-Up:

About 30 days after your last dose of ruxolitinib, blood (about 2 teaspoons) will be drawn
for routine tests.

Inclusion Criteria:

1. Subjects who are able to understand and sign an informed consent document.

2. Subjects 18 years of age or older.

3. Subjects must be diagnosed with CLL/SLL and do not meet the IWCLL criteria for
treatment

4. Patients should be previously untreated or have only been treated with single agent
ibrutinib therapy for a period of < 3 months and were deemed ibrutinib intolerant.

5. Patients whose expected time to CLL/SLL treatment, according to our nomogram posted on
the leukemia protocol priority list, is four years of less.

6. Subjects with hemoglobin values at the screening visit equal to or greater than 12.0
g/dL.

7. Subjects with a platelet count of at least 100 x10^9 at the screening visit.

8. Subjects with an absolute neutrophil count (ANC) of equal to or higher than 0.5 x10^9
at the screening visit.

9. Subject who are willing to undergo a bone marrow aspiration and biopsy and CT scan for
disease burden assessment.

10. Patient who are capable to return to MDACC for follow-up

11. Subjects with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1
or 2

12. Patient must be capable of swallowing the Ruxolitinib capsules (tablets).

Exclusion Criteria:

1. Females who are pregnant or are currently breastfeeding.

2. Subjects of childbearing potential who are unwilling to take appropriate precautions
(throughout the study from screening including 30 days after discontinuation of the
study drug) to avoid becoming pregnant or fathering a child. A) Females of
non-childbearing potential are defined as women who (a) are equal to or greater than
55 years of age with history of amenorrhea for 1 year, OR (b) are surgically sterile
for at least 3 months. B) For females of childbearing potential, or for males,
appropriate precautions are those that are at least 99% effective in preventing the
occurrence of pregnancy. These methods should be communicated to the subjects and
their understanding confirmed: a) Double barrier methods; b) Condom with spermicide in
conjunction with use of an intrauterine device (IUD); c) Condom with spermicide in
conjunction with use of a diaphragm; d) Oral, injectable, or implanted contraceptives;
e) Tubal ligation or vasectomy (surgical sterilization)

3. Subjects with recent history of inadequate bone marrow reserve as demonstrated by
previous transfusions except for acute blood loss (e.g. surgery) in the month prior to
screening.

4. Subjects with inadequate liver or renal function at screening and baseline visits: A)
Alanine aminotransferase (ALT) > 2.5x ULN. B) Modification of Diet in Renal Disease
(MDRD) calculated GFR < 30 mL/min

5. Subjects with active uncontrolled infection or who are HIV positive (Subjects with
acute infections requiring treatment should delay screening/enrollment until the
course of therapy has been completed and the event is considered controlled).

6. Subjects with a history of or a current malignancy except for treated basal or
squamous carcinomas of the skin completely resected.

7. Subjects with clinically significant uncontrolled cardiac disease.

8. Subjects being treated concurrently with any prohibited medications, including
investigational medication, rifampin, St. John's wort, and potent CYP3A4 inhibitors
(excluding ketoconazole) unless continuation of such medications are determined by the
investigator to be in the best interest of the patient. Refer to protocol section
2.2.12 for more details.

9. Subjects who have previously received JAK inhibitor therapy

10. Subjects with active alcohol or drug addiction that would interfere with their ability
to comply with the study requirements.

11. Subjects with any concurrent condition that, in the Investigator's opinion, would
jeopardize the safety of the subject or compliance with the protocol.

12. Subjects who have unknown transfusion history.

13. Patients who cannot comply with the study requirements.