Clinical trial NCT00510289 (phase 2, status: terminated)
Conditions: myelodysplastic syndromes, leukemia, myelomonocytic, chronic
ICD codes: D46.9, D46.C, D46.Z, C93.11, C93.12, C93.10
Drugs: sorafenib
SMILES: CNC(=O)C1=NC=CC(OC2=CC=C(NC(=O)NC3=CC(=C(Cl)C=C3)C(F)(F)F)C=C2)=C1
Reason stopped: 
    early closure of study due to poor response
  
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.