IRB Number:

07-005317

Trial Status:

Open for Enrollment

Phase: I

Why is this study being done?

Patients are being asked to participate in this research study because they have been diagnosed with primary, post polycythemia vera or post essential thrombocythemia myelofibrosis. CC-4047 is a medicine that is chemically similar to a drug called thalidomide. This study is being done to test the safety of CC-4047 and to see what effects (good and bad) it has on patients and their disease.

Who is Eligible to Participate in the Study?

-Age 18 or older
-Diagnosed with primary, post polycythemia vera or post essential thrombocythemia myelofibrosis and patient's disease has not responded to prior treatment with Revlimid or Thalomid
-No prior treatment with CC-4047 (Actimed)

*More specific, detailed eligibility and/ or exclusion criteria are associated with this trial.

What is Involved With this Study?

If agreeing to be in the study, patients will be asked to participate in the following:

Screening:
If deciding to take part in this study, patients will be evaluated to determine if they are eligible to participate in the study. This will take place within 28 days prior to receiving their first dose of CC-4047.

Screening procedures will include:
- A review of patient's medical history, mental health history and treatment history for primary, post polycythemia vera or post essential thrombocythemia myelofibrosis.
- A review of any medications a patient has used in the 28 days prior to starting study drug.
- A review of any blood transfusions a patient may have received in the 28 days prior to the visit.
- A complete physical exam including measurement of patient's spleen and liver.
- Assessment of any discomfort or pain in patient's spleen.
- Bone marrow biopsy and aspiration to confirm patient's diagnosis of primary, post polycythemia vera or post essential thrombocythemia myelofibrosis. The procedure
involves the removal of a small amount of bone marrow fluid and bone marrow tissue through a needle inserted into the bone.
- A 12-lead electrocardiogram (EKG) (a recording of patient's heart's electrical activity).
- Blood sample for routine blood counts, blood chemistry tests, thyroid tests, and other laboratory tests (approximately 4 tablespoons).
- Urine test.
- Pregnancy test for females that are able to get pregnant must be done 10 to 14 days prior to the first dose of CC-4047.
- All patients must agree to the birth control and pregnancy testing guidelines.

Patients will return to the clinic for additional tests prior to beginning study drug. At this visit, they will have the following procedures:

- A complete physical exam including measurement of vital signs (weight, temperature, blood pressure, pulse).
- Review of medications patient is currently taking.
- Review of contraceptive methods patient is using.
- Pregnancy test for females that are able to get pregnant must be repeated 24 hours prior to the first dose of CC-4047.
- Routine blood tests (approximately 4 tablespoons) including routine blood counts, blood chemistry tests, and other laboratory tests, and a pregnancy test within 24
hours of starting study drug.
- Patients will complete an assessment of their quality of life by completing a questionnaire as well as an assessment of possible pain in their spleen.
- The study staff will also assess whether or not patients have experienced any adverse events.

If it is determined that patients are eligible to participate in the study, they will be given study drug and instructed to take it every day for 21 days followed by a 7-day rest (28 days). Twenty-eight days is considered one cycle of treatment.

Because the best dose of CC-4047 for the treatment of this disease is not known, several dose levels of CC-4047 will be studied, ranging from 2.5 to 5 mg. This is the phase I
portion of the study. The dose that patients take will depend on the time that they enter the study and the side effects experienced by those patients that were treated before the other patients.

A patient's dose may be adjusted based on the side effects that the patient experiences. Once the best tolerated dose of CC-4047 is determined additional patients will be treated in this study, starting at that dose level. This is the phase II portion of the study.

Patients are responsible to make sure that they take capsules as directed by the study doctor or his/her staff as well as comply with the study visits as outlined below.

Low-dose aspirin
During the study, the study doctor will ask patients to take low-dose aspirin. If a patient is allergic to aspirin or cannot take aspirin each day (Days 1 to 28) during the treatment phase, the doctor will recommend another therapy (a different medication that a patient may take) to prevent blood clots from forming.

On Day 8, Day 15, and Day 22 of Cycle 1 and Cycle 2
- Pregnancy test, if applicable.
- Routine blood tests.

Beginning at Cycle 3 and each cycle thereafter, the following procedures will be performed:
- A physical exam including measurement of vital signs.
- Assessment of any transfusion a patient may have received since the previous visit.
- A blood sample (approximately 4 tablespoons) for routine blood counts and blood chemistry tests.
- The study staff will ask about any side effects a patient may have experienced.
- Pregnancy testing, if applicable

Every 28 days patients will return their study drug and new study drug will be dispensed at each visit.

Cycle 3 and then every 3 cycles thereafter:
- A blood sample for thyroid tests.
- EKG
- Complete an assessment of a patient's quality of life by completing a questionnaire as well as an assessment of possible pain in the patient's spleen

Discontinuation
When discontinuing from the study, the following procedures will be performed:

- A physical exam including measurement of vital signs.
- Assessment of any transfusions the patient may have received since the previous visit.
- A blood sample (approximately 4 tablespoons) for routine blood counts, blood chemistry tests, thyroid tests and other laboratory tests, and a urine test.
- EKG
- The study staff will ask about any side effects the patient may have experienced.
- Pregnancy testing, if applicable

If patients discontinue the study, they must make every attempt to return to see the study doctor to complete the follow-up procedures.

The drug used in this study is considered investigational, which means it has either not been approved by the U. S. Food and Drug Administration (FDA) for routine clinical use or for the use described in this study. However, the FDA has allowed the use of this drug in this research study.

How long will the Study run?

Patients will be in the study for about one year (up to 12 cycles) or until the side effects are too bad, they do not respond to treatment, they decide to stop, or if their
cancer gets worse.

Sponsor(s): Mayo Clinic

Study Activation/Registration Date: 05/29/2008

IRB Review and Approval Date: 04/11/2008

Study Type: Treatment

Projected Accrual: The plan is to enroll up to 77 patients to participate from Mayo Clinic.

Costs of Study:There may be standard patient care costs related to participating in a cancer research study.

Principal Investigator: Ruben Mesa, MD

Who can I Contact for Additional Information on this Trial?

Complete Request Form for Cancer Clinical Trial Information at Mayo Clinic or
For more information about this study or other clinical trial options, please contact our Mayo Clinic Cancer Center Clinical Trials Referral Office.

• Patients living within the United States, call 507-538-7623


• Patients living outside the United States may call our International Office at 507-284-8884, or e-mail intl.mcr@mayo.edu.

What is/are the Locations of this Clinical Trial?

• Rochester, MN

Last updated: 11/17/2009