The goal of this clinical research study is to learn if CC-4047 (now called pomalidomide) and prednisone can help to control MMM. The safety of this therapy will also be studied.

The Study Drug:

CC-4047 is a drug that may also affect the growth of blood vessels that support tumor growth. If these blood vessels stop growing, it may stop cancer cell growth.

Prednisone is a corticosteroid that is similar to a natural hormone made by your body. Prednisone is often given in combination with other chemotherapy to treat cancer.

Study Drug Administration:

On Days 1- 28 of every 28-day study "cycle," you will take CC-4047 capsule(s) by mouth. You should take the capsule(s), about the same time every day. The capsule(s) should not be opened, broken, or chewed. CC-4047 should be taken without food, at least 2 hours before or 2 hours after a meal. If a dose of CC-4047 is missed, it should be taken as soon as possible on the same day. If it is missed for the entire day, it should not be made up, rather it should be taken at the next scheduled time point.

In order to take part in this study, you must register into and follow the requirements of the POMALYST REMS™ program of Celgene Corporation. This program provides education and counseling on the risks of exposing unborn children to the study drug, and the risks of blood clots and reduced blood counts. You will be required to receive counseling, follow the pregnancy testing and birth control requirements of the program that are appropriate for you, and take surveys regarding how well you are following with the POMALYST REMS™ program.

You will receive prednisone by mouth during the first 3 cycles of therapy. You will take it 1 time a day during Cycle 1. During Cycle 2, you will take a smaller dose 1 time a day. During Cycle 3, you will take the same dose as in Cycle 2, but only 1 time every other day.

On Days 1-28, you will also take low-dose aspirin. This should be taken at the same time as CC-4047. Aspirin is take to help prevent blood clots, which may occur from taking CC-4047. If you are unable to take aspirin, your study doctor will have you take another drug.

You will be given a study "diary". In this diary, you will record when you take each dose of the study drug. You will return any unused study drug and empty bottles at each visit.

Study Visits:

On Day 1 of Cycles 1 and 2, the following tests and procedures will be performed:

• You will have a physical exam, including measurements of your vital signs (blood pressure, temperature, and heart rate) and weight.
• You will be asked about any drugs you are taking and about recent blood transfusions you may have had.
• You will have a performance status evaluation.
• Blood (about 1 tablespoon) will be drawn for routine tests.

On Days 1, 8, 15, and 22 of Cycles 1 and 2, blood (about 4 teaspoons) will be drawn for routine tests.

On Day 28 of each cycle, the following tests and procedures will be performed:

• You will be asked about any drugs you are taking and about recent blood transfusions you may have had.
• You will be asked about any birth control methods you are using.
• Blood (about 4 tablespoons) will be drawn for routine tests.
• You will be asked about any new side effects or medical conditions you may have experienced.
• You will complete a questionnaire about your quality-of-life as well as an assessment of possible pain in your spleen. (Cycles 1 and 2 only)

On Day 28 of cycles 1,2,3 and every third cycle (Cycle 6, 9, and so on), the following tests and procedures will be performed:

• You will have a physical exam, including measurement of yur vital signs and weight.
• Measurements of your spleen and/or liver will be taken.
• You will have a performance status evaluation.

On Day 28 of every sixth cycle (Cycle 6, 12 and so on)the following tests and procedures will be performed:

• Blood (about 4 teaspoons) will be drawn to test your thyroid function.
• You will have an ECG.
• Response of disease to therapy will be assessed. Bone marrow biopsy and aspirate will be done to confirm a complete response if your doctor thinks it is needed.

Pregnancy Testing:

Women who are able to have children will have a pregnancy test every week during Cycle 1, and then every 28 days after that if your menstrual cycle is regular (If your menstrual cycle is not regular, you will have a blood pregnancy test every 2 weeks). These pregnancy tests will be part of a routine blood draw.

Length of Study:

You will remain on study treatment as long as the therapy is beneficial to you. You will be taken off study early if the disease gets worse or intolerable side effects occur.

End-of-Treatment Visit:

Once you are off study, you will have an end-of-study visit. At this visit, the following tests and procedures will be performed:

• You will have a physical exam, including measurements of your vital signs and measurements of your spleen and/or liver.
• You will have an ECG.
• You will be asked about any drugs you are taking and about any blood transfusions you may have had.
• Blood (about 4 tablespoons) and urine will be collected for routine tests and thyroid function tests. This routine blood draw will include a pregnancy test for women who are able to have children.
• You will be asked about any side effects you may have experienced.

Follow-Up Visit:

Women who are able to have children will have a blood (about 1 tablespoon) pregnancy test 28 days after the last dose of study drug. If your periods are irregular you will have 2 blood (about 1 tablespoon each time) pregnancy tests, one 14 days after the last dose of study drug and another 28 days after the last dose of study drug. Response of disease to therapy will be assessed at follow-up 28 days after last dose of study drug.

This is an investigational study. CC-4047 (pomalidomide) is FDA approved and commercially available for the treatment of certain types of MM. Its use in this study is investigational.

Prednisone is FDA approved and commercially available.

Up to 70 patients will take part in this study. All will be enrolled at M. D. Anderson.

Inclusion Criteria:

1. Must be >/= 18 years of age at the time of voluntarily signing an Institutional Review Board/Independent Ethics Committee (IRB/IEC) - approved informed consent form.
2. Must be diagnosed with myelofibrosis requiring therapy including myelofibrosis with myeloid metaplasia (MMM), de novo presentation (i.e. agnogenic myeloid metaplasia [AMMM], and developing after an antecedent history of Polycythemia vera (i.e., post-polycythemic myeloid metaplasia [PPMM]), or essential Polycythemia (i.e., post thrombocythemic myeloid metaplasia [PTMM]).
3. Screening total hemoglobin level < 10 g/dL or transfusion-dependent anemia defined as per International Working Group (IWG) criteria (transfusion dependency defined by a history of a least 2 units of red blood cell transfusions in the last 28 days for hemoglobin < 8.5 g/dL that was not associated with overt bleeding)
4. Must have adequate organ function as demonstrated by the following </= 14 days prior to starting study drug: ·Alanine transaminase (ALT) (SGOT) and Aspartate aminotransferase (AST) (SGPT) </= 3 x upper limit of normal (ULN), [unless upon judgment of the treating physician, it is believed to be due to extramedullary hematopoiesis (EMH)] ·Total bilirubin < 3 x ULN or Direct Bilirubin < 2 x ULN ·Serum creatinine </= 2.5 mg/dL ·Absolute neutrophil count >/= 1,000/µL (>/=1.0 x 10^9/L) ·Platelet count >/= 50,000/µL (>/=50 x 10^9/L)
5. Subjects must be willing to receive transfusion of blood products
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2 at screening.
7. Must be willing to adhere to the study visit schedule and other protocol requirements.
8. No active malignancies with the exception of basal cell or squamous cell carcinoma of the skin, or carcinoma (in situ) of the cervix or breast
9. All study participants must be registered into the mandatory POMALYST REMS™ program, and be willing and able to comply with the requirements of the POMALYST REMS™ program.
10. Females of reproductive potential (FCBP†) must adhere to the scheduled pregnancy testing as required in the POMALYST REMS™ program. Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin).

Exclusion Criteria:

1. Known positive status for HIV, hepatitis B carrier, or active hepatitis C infection.
2. The use of any growth factors, cytotoxic chemotherapeutic agents (e.g. hydroxyurea), corticosteroids, or experimental drug or therapy within 14 days of starting CC-4047 and/or lack of recovery from all toxicity from previous therapy to grade 1 or better.
3. Any serious medical condition or psychiatric illness that would prevent, (as judged by the treating physician) the subject from signing the informed consent form or any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
4. Pregnant or lactating females
5. Prior use of CC-4047
6. Currently enrolled on another clinical trial or receiving investigational agent

Up to 3 years