Sorafenib in Myelodysplastic Syndrome
Condition: Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic
MeSH terms: Preleukemia; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes; Syndrome
Intervention: Sorafenib
Intervention description: 400 mg twice a day until progression or unacceptable toxicity develops.
Intervention MeSH terms: Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Sorafenib; Myelodysplastic Syndromes; MDS

Summary:

      The purpose of this study is to evaluate the efficacy of sorafenib in patients with
      Myelodysplastic Syndrome (MDS). Eligible subjects will receive Sorafenib administered at
      400mg orally twice a day, given on days 1-28 of a 28-day cycle. Patients will be evaluated
      for hematological response after 2 cycles and then every 3 cycles thereafter for a maximum of
      5 years from study entry. If a patient achieves a complete response they may receive an
      additional 6 cycles of therapy beyond documentation of complete response unless unacceptable
      toxicity occurs. For patients with partial response, hematological improvement or stable
      disease they will continue treatment until relapse, progression of disease, or unacceptable
      toxicity occurs.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have a diagnosis of primary or therapy-related myelodysplastic syndrome
             or myelodysplastic/ myeloproliferative disorders as defined by the WHO

               -  Refractory anemia with excess blasts - 1 or 2

               -  Chronic myelomonocytic leukemia type 2

               -  Refractory anemia, refractory anemia with ringed sideroblasts, refractory
                  cytopenia with multilineage dysplasia, refractory cytopenia with multilineage
                  dysplasia with ringed sideroblasts, 5q- syndrome, myelodysplastic syndrome
                  unclassified or chronic myelomonocytic leukemia type 1 if at least one of the
                  following criteria is met: HgB < 10 g/dl, Platelets < 50,000/ul,ANC < 1,000 ul,
                  Transfusion dependent defined as 2 transfusions within an 8 week period.

          -  Patients may have low, intermediate-1, intermediate-2 or high risk MDS or CMML.

          -  Patients are eligible without regard to prior treatment status except for allogenic
             bone marrow transplant.

          -  Patients must be 18 years of age or older.

          -  Patient has an estimated or measured creatinine clearance ≥30 ml/min at study
             enrollment.

          -  AST, ALT, total bilirubin ≤ than 2.5 times the upper limit of normal.

          -  ECOG performance status of 0-2.

          -  Voluntary written informed consent before performance of any study-related procedure
             not part of normal medical care.

          -  Female subject is either post-menopausal or surgically sterilized or willing to use an
             acceptable method of birth control.

          -  Male subject agrees to use an acceptable method for contraception for the duration of
             the study therapy and for 2 weeks after study completion.

        Exclusion Criteria:

          -  Female subject is pregnant or lactating. Confirmation that the subject is not pregnant
             must be established by a negative serum B-human chorionic gonadotropin (B-hCG)
             pregnancy test result within 2 weeks of enrollment. Pregnancy testing is not required
             for post-menopausal or surgically sterilized women.

          -  Patient has received other investigational drugs for this disease within 14 days of
             enrollment

          -  No growth factor support with erythropoietin, GCSF, or GMCSF within 28 days of
             enrolling in the study.

          -  Serious medical or psychiatric illness likely to interfere with participation in this
             clinical study.

          -  Patients with another malignancy within the last one year (from documentation of
             remission) other than basal or squamous cell skin cancer or CIS of the cervix.

          -  Patients who underwent allogeneic stem cell transplant will be excluded.

          -  History of leukemia (having more than 20% blasts in blood or marrow)

          -  Current treatment with coumadin, heparin and its derivatives.

          -  Major surgery (including needle biopsy of visceral organs) for 1-month prior to study
             and fully recovered. In addition, no placement of a subcutaneous or tunneled venous
             access device for 3 days prior to study and adequately healed.

          -  Significant cardiac or vascular events within 6 months: acute MI, unstable angina,
             severe peripheral vascular disease (ischemic pain at rest class 3 or worse,
             non-healing ulcers/wounds, congestive heart failure (NHYA class ≥ 2), uncontrolled
             cardiac arrhythmias, and disseminated intravascular coagulation.

          -  No use of hematopoetic growth factors within 4 weeks of starting sorafenib.

          -  Known severe hypersensitivity to Sorafenib or any component of the formulation.

          -  Caution should be exercised with the concomitant use of other CYP3A4 inducers, such as
             rifampin, St. John's Wort, phenytoin, phenobarbital and dexamethasone.

          -  Uncontrolled hypertension with a systolic blood pressure greater than 160 or a
             diastolic blood pressure greater than 100 despite treatment.