- 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
- 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.
- 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
- 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
- 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.