Lenalidomide for Patients With Myelofibrosis (MF)

The goal of this clinical research study is to learn if lenalidomide in combination with prednisone can help to control myelofibrosis. The safety of lenalidomide and prednisone for the treatment of myelofibrosis will also be studied.

Lenalidomide is designed to change the body's immune system. It may also interfere with the development of tiny blood vessels that help support tumor growth. Therefore, in theory, it may decrease or prevent the growth of cancer cells. Prednisone is designed to improve the results of lenalidomide and to help reduce the side effects.

If you are found to be eligible to take part in this study, you will take 1-2 capsules of lenalidomide by mouth daily. You will take lenalidomide daily for 21 days followed by 1 week rest. This 28-day period is called a study "cycle."

Swallow lenalidomide capsules whole with water at the same time each day. Do not break, chew or open the capsules.

If you miss a dose of lenalidomide, take it as soon as you remember on the same day. If you miss taking your dose for the entire day, take your regular dose the next scheduled day (do NOT take double your regular dose to make up for the missed dose).

You will take prednisone by mouth every day during Cycles 1-2, and every other day during Cycle 3. You may only take prednisone for Cycles 1-3.

You will be given a study drug diary. In this diary, you will record when you take the study drug(s).

During treatment, blood (about 1 tablespoon) will be drawn once every 1-2 weeks. The tests may be repeated more frequently to check for side effects.

Every month for the first 3 months, and then every 3 months, until you complete 24 cycles, you will have a study visit. You will have a bone marrow biopsy/aspirate every 3 months. Lenalidomide will be provided to you as a monthly (28-day) supply.

Following the completion of Cycle 24, you will have a study visit every 6 months. You will have a bone marrow biopsy/aspirate every 6 months. Lenalidomide will be provided to you as a monthly (28-day) supply.

Depending on side effects and the activity of the study drug against the disease, your dose of the study drug may be increased or decreased.

You may stay on study for as long as you are benefitting. You will be taken off study if you are not or are no longer benefitting or intolerable side effects occur.

This is an investigational study. Lenalidomide and prednisone are both FDA approved and commercially available. Lenalidomide is approved by the Food and Drug Administration (FDA) for the treatment of patients with transfusion-dependent anemia due to Low- or Intermediate-1-risk myelodysplastic syndromes associated with the chromosome 5 abnormality with or without other chromosome abnormalities. Lenalidomide is also approved in combination with dexamethasone for the treatment of patients with multiple myeloma that have received at least one prior therapy. MDS and MM are cancers of the blood. It is currently being tested in a variety of cancer conditions. In this case it is considered experimental. Prednisone is on the market for many different things but not specifically for Myelofibrosis. The use of these drugs in combination is considered investigational in this study. Up to 41 patients will take part in this study. All will be enrolled at M. D. Anderson.

• Drug: Lenalidomide
  Oral 10 mg daily/days 1-21 of 28 day cycle
• Drug: Prednisone
  Starting dose oral 30 mg daily of 28 day cycle

Inclusion Criteria:

1. Diagnosis of myelofibrosis requiring therapy, including those previously treated and relapsed or refractory, or if newly diagnosed, with intermediate or high risk according to Lille scoring system (risk factors are: Hb < 10 g/dl, WBC < 4 or > 30 x 109/L; risk group: 0 factor(s) = low, 1 factor(s) = intermediate, 2 factor(s) = high) or with symptomatic splenomegaly
2. Understanding and voluntary signing an IRB-approved informed consent form.
3. Age >/= 18 years at the time of signing the informed consent.
4. Disease-free of prior malignancies for >/= 2-years with exception of basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.
5. ECOG performance status 0 to 2.
6. Patients must have adequate organ function as demonstrated by the following: Total bilirubin </= 2.0 mg/dL (unless higher due to MF); Serum creatinine </= 2.0 mg/dL (unless higher due to MF); Absolute neutrophil count >/= 1 x 10^9/L; ALT </= 3 x upper limit of normal (unless higher due to MF).
7. Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing.
8. Continuation of 7. Men must agree to use a condom during sexual contact with a female of child bearing potential even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. See Appendix J: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods
9. footnote to no 7. † A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
10. All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®

Exclusion Criteria:

1. Use of any other standard (e.g. hydroxyurea, anagrelide, growth factors) or experimental drug or therapy within 28 days of starting lenalidomide and/or lack of recovery from all toxicity from previous therapy to grade 1 or better.
2. Known prior clinically relevant hypersensitivity reaction to thalidomide, including the development of erythema nodosum if characterized by a desquamating rash.
3. Prior therapy with lenalidomide.
4. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
5. Suspected Pregnancy. Pregnant or lactating females.
6. 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.
7. Known positive for HIV or infectious hepatitis, type A, B or C.
8. Known prior clinically relevant hypersensitivity to prednisone.
9. Participants with a heart rate (HR) of less than or equal to 50, as a HR less than 50 indicates underlying cardiac abnormalities.
10. Participants with prior history of thromboembolic disease (i.e.-deep venous thrombosis [DVT] or pulmonary embolism [PE]) within the last six months, as Lenalidomide has demonstrated a significantly increased risk of DVT or PE.