A Phase II Study of MS-275, in Combination With GM-CSF Treating Relapsed and Refractory Myeloid Malignancies

Inclusion Criteria:

In general, patients with MDS and relapsed or refractory AML, who are not eligible for a potentially curative myeloablative allogeneic stem cell transplant or who are considered poor candidates for such a procedure due to age, medical co-morbidities, or lack of a suitable donor, will be considered for participation in the proposed trial.

Disease Specific Inclusion Criteria:

• MDS
• Relapsed AML
• Untreated AML

Additional Criteria:

1. Age > 18.
2. JHOC confirmed and documented diagnosis of either AML or MDS within 12 weeks of trial enrollment. Patients with MDS are restricted to those with IPSS of INT-2 or high risk.
3. Patients must have relatively stable bone marrow function for more than seven days prior to enrollment on the study. WBC count doubling within seven days of enrollment or WBC greater than 10 x 103/dL would indicate unstable bone marrow function.
4. ECOG performance status of 0, 1, 2.
5. Patient or caregiver must be willing to perform subcutaneous injection.

6. Patients must have the following end organ function:

   • Serum creatinine < 2.0 mg/dL
   • Total serum bilirubin < 1.6 mg/dL, unless secondary to hemolysis.
   • SGOT/SGPT each < 3 times the upper limit of normal unless disease related
   • Hemoglobin should be at least 8 gm/dL at the time of protocol entry. Patients may receive transfusions to achieve this level.
7. Patients must not have received treatment for their myeloid disorder within 2 weeks of beginning the trial. Treatments include the use of chemotherapy, hematopoietic growth factors, and biologic therapy such as monoclonal antibodies. The exception is the use of hydroxyurea for patients with WBC > 30 x 103/μL. This duration of time appears adequate for wash out due to the relatively short-acting nature of most anti-leukemia agents.
8. Patients must have recovered from all toxicities (to grade 0 or 1) associated with previous treatment.
9. Patients must not have any clinical symptoms of active CNS disease. If CNS disease is suspected, patient must have LP with negative cytology.
10. All women of potential child bearing must have negative urine or serum B-HCG prior to enrollment.
11. All women of potential child bearing must agree to use adequate birth control throughout the trial period. All men must agree to use barrier contraceptive throughout the trial period.
12. Patients must be able to provide informed consent and to return to clinic for adequate follow up as required by the protocol.

Exclusion Criteria:

1. Diagnosis of RA with 5q- syndrome
2. Peripheral leukemia with blast count > 30 x 103/dL, uncontrolled with hydroxyurea.
3. Age < 18
4. ECOG performance status > 3
5. Patients with untreated or progressive infections
6. Patients with active CNS disease
7. Patients with a previous history of intolerance to GM-CSF
8. Pregnant or lactating women