Ruxolitinib and Lenalidomide for Patients With Myelofibrosis
Condition: Myeloproliferative Diseases
MeSH terms: Primary Myelofibrosis; Myeloproliferative Disorders
Intervention: Ruxolitinib; Lenalidomide; Prednisone
Intervention description: 15 mg by mouth twice daily (BID), continuously in 28-day cycles.; 5 mg by mouth each day on days 1-21, followed by 7 days of no therapy of each 28 day cycle.; Prednisone will be added for patients who have not responded after 3 cycles of therapy.
30 mg by mouth a day during cycle 4, 15 mg/day during cycle 5, and 15 mg every other day during cycle 6, and then it will be discontinued.
Intervention MeSH terms: Prednisone; Lenalidomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Myeloproliferative Diseases; Myelofibrosis; Post essential thrombocythemia/polycythemia vera; Ruxolitinib; INCB018424; Lenalidomide; CC-5013; Revlimid; Prednisone; Interactive Voice Response System; IVR

Summary:

      The goal of this clinical research study is to learn if the combination of ruxolitinib and
      lenalidomide can help to control MF. The safety of this study drug combination will also be
      studied.

      Ruxolitinib is designed to stop certain proteins (called JAK1 and JAK2) that are found in MF
      cells from sending signals that may lead to the growth of cancer cells.

      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. This may decrease the
      growth of cancer cells.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Diagnosis of myelofibrosis (either primary or post essential
             thrombocythemia/polycythemia vera) requiring therapy, including those previously
             treated and relapsed or refractory, or if newly diagnosed, with intermediate-1 or -2
             or high risk according to International Working Group (IWG) criteria.

          2. Understanding and voluntary signing an IRB-approved informed consent form.

          3. Age equal to or greater than 18 years at the time of signing the informed consent.

          4. Disease-free of prior malignancies for equal to or greater than 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: a. Direct
             bilirubin equal to or less than 2.0 mg/dL, b. Serum creatinine equal to or less than
             2.0 mg/dL., c. SGPT equal to or less than 3 x upper limit of normal

          7. Females of childbearing potential (FCBP)(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)

          8. Cont. from 7: must have a negative serum or urine pregnancy test with a sensitivity of
             at least 50 mIU/mL within 10 to 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. 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.

          9. All study participants must be registered into the mandatory RevAssist® program, and
             be willing and able to comply with the requirements of RevAssist®.

         10. Platelets >/= 100000/uL

         11. ANC >/= 1000/uL

        Exclusion Criteria:

          1. Use of any other standard (e.g. hydroxyurea, anagrelide, growth factors) or
             experimental drug or therapy within 14 days or 5-half lives, whichever is longer, of
             starting study therapy 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 or ruxolitinib.

          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 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.

         10. Known to have a hypercoagulability syndrome (eg: antithrombin III, deficiency,
             anticardiolipin syndrome etc…)

         11. Concurrent use of strong inducers or strong inhibitors of CYP3A4 (strong inducers are
             rifampin and St. John's Worth, carbamazepine, phenytoin, and barbiturates such as
             phenobarbital; strong inhibitors are HIV-antivirals, clarythromycin, itraconazole,
             ketoconazole, nefazodone, and telithromycin).

         12. Incarcerated persons are excluded from the protocol.