Ruxolitinib Phosphate and Danazol in Treating Anemia in Patients With Myelofibrosis
Condition: Anemia; Primary Myelofibrosis; Secondary Myelofibrosis
MeSH terms: Anemia; Primary Myelofibrosis
Intervention: ruxolitinib phosphate; danazol; quality-of-life assessment; questionnaire administration
Intervention description: Given PO; Given PO; Ancillary studies; Ancillary studies
Intervention MeSH terms: Danazol; Janus Kinase Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II pilot trial studies how well ruxolitinib phosphate and danazol work in treating
      anemia in patients with myelofibrosis. Ruxolitinib phosphate and danazol may cause the body
      to make more red blood cells. They are used to treat anemia in patients with myelofibrosis.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histological confirmation of primary myelofibrosis (MF), post polycythemia vera (PV)
             or post essential thrombocythemia (ET) myelofibrosis (intermediate 1, intermediate II
             or high risk) requiring medical therapy

          -  Anemia is required for trial entry (defined as hemoglobin < 10g/dL or transfusion
             dependent [having needed a transfusion anytime in the past 6 months])

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 at study
             entry

          -  Absolute neutrophil count (ANC) >= 1000/uL

          -  Platelet count >= 50,000/uL

          -  Serum creatinine =< 1.5 x the upper limit of normal (ULN)

          -  Total bilirubin =< 1.5 x ULN; if total bilirubin is > 1.5 x ULN, a direct bilirubin
             should be performed and must be < 1.5mg/dL

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN; higher
             values (i.e., =< 5 x ULN) are allowed if clinically compatible with hepatic
             extramedullary hematopoiesis

          -  Life expectancy of >= 6 months

          -  Patient able to provide voluntary written informed consent to participate

          -  Willing to comply with scheduled visits, treatment plans, laboratory assessments, and
             other study-related procedures

          -  Negative pregnancy test done =< 7 days prior to registration, for women of
             childbearing potential only

        Exclusion Criteria:

          -  Any chemotherapy (e.g., hydroxyurea), immunomodulatory drug therapy (e.g.,
             thalidomide, interferon-alpha), immunosuppressive therapy, corticosteroids > 10 mg/day
             prednisone or equivalent, or growth factor treatment (e.g., erythropoietin), hormones
             (e.g., androgens, danazol) =< 14 days prior to registration; note: patients who are on
             ruxolitinib may continue on without a 14 day wash out at the treating physician's
             discretion

          -  Major surgery =< 28 days or radiation =< 6 months prior to registration

          -  Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
             of the investigator, would make the patient inappropriate for entry into this study or
             interfere significantly with the proper assessment of safety and toxicity of the
             prescribed regimens

          -  Active acute infection requiring antibiotics

          -  Uncontrolled congestive heart failure (New York Heart Association classification 3 or
             4), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral
             artery bypass, graft surgery, transient ischemic attack, or pulmonary embolism within
             3 months prior to registration

          -  Participation in any study of an investigational agent (drug, biologic, device) =< 30
             days, unless during non-treatment phase

          -  Any of the following:

               -  Pregnant women

               -  Nursing women

               -  Men or women of childbearing potential who are unwilling to employ adequate
                  contraception

          -  Known human immunodeficiency virus or acquired immunodeficiency syndrome-related
             illness

          -  Clinically active hepatitis B or C

          -  Active malignancy other than MF, except adequately treated basal cell carcinoma and
             squamous cell carcinoma of the skin, cervical carcinoma in situ or other malignancies
             that have been stable and off therapy for 5 years

          -  Patient currently taking simvastatin, or lovastatin at a dose greater than 10 mg/day

          -  Men with prostate specific antigen (PSA) > 4 ng/ml or with uncontrolled benign
             prostatic hypertrophy

          -  Patient received prior combination treatment with ruxolitinib and danazol together;
             note: previous treatment with ruxolitinib and/or danazol as single agent therapy is
             allowed

          -  Receiving any medications or substances that are strong or moderate inhibitors of
             cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4); use of the following
             strong or moderate inhibitors are prohibited =< 7 days prior to registration

               -  Strong inhibitors of CYP3A4:

                    -  Indinavir (Crixivan)

                    -  Nelfinavir (Viracept)

                    -  Atazanavir (Reyataz)

                    -  Clarithromycin (Biaxin, Biaxin XL)

                    -  Itraconazole (Sporanox)

                    -  Ketoconazole (Nizoral)

                    -  Nefazodone (Serzone)

                    -  Saquinavir (Fortovase, Invirase)

                    -  Telithromycin (Ketek)

               -  Moderate inhibitors of CYP3A4

                    -  Erythromycin (Erythrocin, E.E.S., Ery-Tab, Eryc, EryPed, PCE)

                    -  Fluconazole (Diflucan)

                    -  Grapefruit juice

                    -  Verapamil (Calan, Calan SR, Covera-HS, Isoptin SR, Verelan)

                    -  Verelan PM

                    -  Diltiazem (Cardizem, Cardizem CD, Cardizem LA, Cardizem SR, Cartia XT,
                       Dilacor XR, Diltia XT, Taztia XT, Tiazac)