Nuvigil in Treatment of Cancer-Related Fatigue in Chronic Myeloid Leukemia Patients

The Study Drug:

Armodafinil is designed to help promote wakefulness in patients suffering from fatigue.

Study Groups:

If you are found to be eligible to take part in this study, you will take 3 tablets each day
during Weeks 1, 2, 4, and 5. You will not take any tablets during Week 3.

You will be randomly assigned (as in the flip of a coin) to a study group. The tablets you
receive will depend on which study group you are in. You will have an equal chance of being
assigned to either group:

- If you are in Group 1, you will take armodafinil during Weeks 1 and 2 and a placebo
during Weeks 4 and 5. A placebo is a tablet that looks like the study drug but has no
active ingredients.

- If you are in Group 2, you will take a placebo during Weeks 1 and 2 and armodafinil
during Weeks 4 and 5.

Neither you nor the study staff will know to which group you are assigned. However, if
needed for your safety, the study staff will be able to find out what you are receiving at
any time.

You will be given a fatigue diary and a drug diary. You will fill out the fatigue diary
every day by answering 2 questions about fatigue. You will fill out the drug diary every day
by writing when you take the study drug/placebo. You will return any unused drug/placebo at
the end of Weeks 2 and 5.

At Week 5, you will be asked if you preferred the first period (Weeks 1 and 2 of the study)
or the second period (Weeks 4 and 5 of the study). If your doctor thinks it is in your best
interest and you are benefitting at this point, you will be able to continue taking the
study drug and you will have additional study visits.

If you are one of the patients selected for the PK testing, the final results of the PK
testing for your entire group will need to be completed before you can start the long term
use of the study drug. If you take the study drug after Week 5, you will take 3 tablets
every day for the rest of the time that you take the study drug.

Study Visits:

At the end of Weeks 1, 3, and 4:

- You will be asked about any symptoms that you may be having and about any other drugs
that you may be taking.

- You will complete 2 questionnaires about fatigue and activity. It will take about 10
minutes to complete these questionnaires.

- Your blood pressure will be measured (Weeks 1 and 4 only).

At the end of Weeks 2 and 5:

- You will have a physical exam, including measurement of your weight and vital signs.

- You will complete the same questionnaires you completed at screening.

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

- If you were selected for PK testing during screening, you will also have PK blood
samples drawn at the end of Week 2 and Week 5.

- You will complete the series of tests that check your memory, motor skills, and
thinking that you completed at screening.

At Weeks 10, 15, 20, and 25:

- You will be asked about any symptoms that you may be having and about any other drugs
that you may be taking.

- You will complete the 2 questionnaires about fatigue and activity.

- Your blood pressure will be measured.

If you are not scheduled to come to MD Anderson at Weeks 1, 3, 4, 10, 15, 20, and 25, the
procedures to be performed at these times can be performed at home. You will be called and
asked the questions described in these visits. You will take 2 separate blood pressure
measurements 5 minutes apart for each day and report results to the research staff over the
telephone. If you choose to take your blood pressure measurements at home, you will be
provided with a home blood pressure monitor at screening and taught how to use it. The
monitor will be returned to study staff at the end of the study.

Length of Study:

You may continue taking the study drug as part of this study for up to 24 weeks. If you are
benefiting after 24 weeks, you may continue taking the study drug off study. If you are one
of the patients selected for the PK testing, the final results of the PK testing for your
entire group will need to be completed before you can start the long term use of the study
drug. You will be taken off study at any time if you have intolerable side effects or if the
study doctor thinks it is in your best interest.

End of Treatment:

About 6 months after the end of Week 5, the following tests and procedures will be
performed:

- You will complete the same questionnaires you completed at screening.

- You will complete the series of tests that check your memory, motor skills, and
thinking that you completed at screening.

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

- You will have a physical exam, including measurement of your weight and vital signs.

Follow-Up:

The study staff will call you about 30 days after your last dose of study drug and ask about
any symptoms or complaints you may have had, as well as about any other drugs you may be
taking. This call will last about 10 minutes.

This is an investigational study. Armodafinil is FDA approved and commercially available to
help improve wakefulness in adults who experience excessive sleepiness. Its use in
cancer-related fatigue is investigational.

Up to 60 patients will take part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. Patients with CML on imatinib, dasatinib or nilotinib (or any other FDA approved
tyrosine kinase inhibitor (TKI) for CML)

2. Must be >/= 18 years of age

3. Must have "fatigue worst" on The Brief Fatigue Inventory > or = 4

4. Women of childbearing potential (not surgically sterile or 2 years postmenopausal)
must use a medically accepted method of contraception (refer to protocol for
acceptable methods of contraception). Men not surgically sterile or who are capable
of producing offspring must practice abstinence or use a barrier method of birth
control. Both men and women must agree to continue use of this method for the
duration of the study and for 30 days after participation in the study.

5. Informed consent must be signed

6. Patient should have at least a complete cytogenetic response (CCyR) sustained for the
last 6 months

7. Patient should be receiving stable dose of TKI for at least 3 months (i.e. no
increase or decrease in dose during this period) and should not have treatment
interruptions for more than 7 consecutive days during this time period unless this
was exclusively because of fatigue.

8. Females must have a negative serum pregnancy test within 48 hours prior to beginning
treatment on this trial

9. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1
or 2 at baseline

Exclusion Criteria:

1. History of hypersensitivity or allergy to armodafinil, modafinil or any component of
the formulation of armodafinil.

2. History of or current seizures, glaucoma, major psychiatric diagnosis (psychiatric
illness that required hospitalization), narcolepsy or Tourette's syndrome

3. History of severe headaches or increased agitation within the last 90 days prior to
enrollment

4. History of clinically significant uncontrolled pulmonary or cardiac disease
(uncontrolled is defined as patients requiring changes in dose and/or start of a new
course of treatment in the last 30 days). This may include disease states as
congestive heart failure, cardiac arrhythmias, coronary artery disease, chronic
obstructive pulmonary disease and asthma)

5. Uncontrolled hypertension. Patients that have not been on a stable treatment dose for
the past month or have a systolic blood pressure consistently (consistently is
defined as 3 consecutive blood pressure readings within the last 30 days) greater
than 150 mm Hg or diastolic pressure consistently greater than 85 mm Hg

6. History of fibromyalgia

7. History or current abuse of alcohol or drugs

8. Moderate to severe depression as measured on the Depression Anxiety Stress Scale
(DASS-21)

9. If taking antidepressants, no changes in dose and/or no start of new course of
treatment in the last 30 days

10. Currently taking psychostimulants (including appetite suppressants), L-Monoamine
oxidases (MAO) inhibitors, anticoagulant therapy, anticonvulsant therapy or current
consumption of alcohol within 8 hours of enrollment.

11. Current use of corticosteroids, stimulants, or other medications used to improve
fatigue symptoms. Topical corticosteroids or occasional, intermittent doses of
systemic steroids (e.g., for pre-medications, etc) are allowed

12. On clinical trials listing Armodafinil as a prohibited medication within the last 30
days of enrollment

13. Use of the following herbals or supplements for fatigue relief within the last 30
days (including dehydroepiandrosterone (DHEA), SAMe, ginkgo, ginseng, green, black or
Chinese tea, ephedra (aka-ma-huang), popotillo and Mormon tea

14. Any coexisting medical condition or taking any concomitant medication that is likely
to interfere with the safe administration of armodafinil

15. Hemoglobin < 8 gm/dl at time of enrollment

16. Albumin value 50% lower than the lower limit of normal

17. Evidence of hepatic impairment (total bilirubin > or = 2.5 times Upper limits of
normal (ULN), serum glutamate pyruvate transaminase (SGPT) > or = 2.5 times ULN)

18. Evidence of renal impairment (serum creatinine > 2.5 times ULN)

19. If taking opioids, anxiolytics, and/or hypnotics, no changes in dose and/or no start
of new course of treatment in the last 30 days

20. Patients who were ever in blast phase of CML

21. Female patients who are pregnant or breastfeeding

22. History of mitral valve prolapse documented by cardiac study.

23. Patients with history or current suicidal ideation

24. Currently taking strong cytochrome P450 3A4 (CYP3A4) inducers (including but not
limited to phenobarbital, phenytoin, rifampin,and troglitazone); strong CYP3A4
inhibitors (including but not limited to ketoconazole, itraconazole, clarithromycin,
ritonavir, indinavir, nelfinavir, saquinavir, nefazodone, telithromycin and
grapefruit juice)

25. Patients who have been transplanted and are on immunosuppressive therapies that may
interfere with TKI