Phase II Study of Azacitidine and Sargramostim as Maintenance Treatment for Poor-Risk AML or MDS

We propose a phase II study to determine the impact of maintenance therapy with 5-azacytidine
and GM-CSF in patients with poor-risk AML or MDS, who are in remission after definitive
treatment with either stem cell transplant or cytarabine-based consolidation chemotherapy.

In order to precede relapse and to avoid lead time bias, treatment would need to commence
within 185 days of definitive therapy. Furthermore, approximately 50% of relapses occur
within the first year and up to 80% within two years after SCT, therefore we would limit the
duration of maintenance therapy to one year, followed by two years of follow-up.

Inclusion Criteria:

1. Age > 6 months

2. Initial diagnosis of poor -risk AML or MDS (defined in section 3.2), treated with
either stem cell transplant or cytarabine-based consolidation chemotherapy, within the
past 60-185 days

3. ECOG performance status 0-2

4. No morphologic evidence of leukemia or active MDS as determined by JHH
Hematopathologist independent review of a bone marrow aspirate and biopsy done
following the completion of therapy and within 14 days prior to enrollment

5. Peripheral blood count recovery: Neutrophil count ≥ 1000 /µL, platelet count ≥ 50x 109
/µL without platelet transfusions, and adequate hematocrit independent of red cell
transfusions .

6. No evidence of extramedullary leukemia, such as CNS or soft tissue involvement

7. Adequate end organ function as measured by the following: AST and ALT < 4 x normal,
total serum bilirubin < 2 x upper limit normal (unless due to hemolysis, Gilbert's
syndrome, or ineffective erythropoiesis), creatinine < 2 x upper limit of normal

8. Ability to give informed consent

9. In agreement to use an effective barrier method of birth control to avoid pregnancy
during the study and for a minimum of 30 days after study treatment, for all male and
female patients who are fertile

Exclusion Criteria:

1. Patients with untreated or uncontrolled infections

2. Patients with untreated or uncontrolled grade 3 or 4 GVHD

3. Pregnancy and lactation

4. Concurrent use of any other investigational agents.

5. Known HIV-positive patients.

6. Known hypersensitivity to 5AC or GM-CSF