RAD001(Everolimus) in Treating Patients With Myelodysplastic Syndromes

OBJECTIVES:

Primary

- Determine the clinical activity (improvement in erythroid response and/or improvement in
other cytopenias, bone marrow morphology/cytogenetics) of RAD001(everolimus) in patients
with low or intermediate-1 risk myelodysplastic syndromes.

- Assess the toxicity of this drug in these patients.

Secondary

- Examine laboratory correlates (S6K1 levels, angiogenesis pre- and post-treatment) and
determine how these correlates correspond to dosing and clinical activity of
RAD001(everolimus).

- Evaluate the presence of HLA-DR15 and cytotoxic T-cell populations in patients pre- and
post-treatment and correlate this with response to treatment.

- Examine the incidence of the null GSTT-1 phenotype in myelodysplastic syndromes patients
and correlate this with response to RAD001(everolimus).

OUTLINE: Patients receive oral RAD001(everolimus) once daily on days 1-21. Courses repeat
every 28 days in the absence of disease progression or relapse.

Blood samples are collected periodically during study. Samples are analyzed for S6K1
activity, effector T cells by flow cytometry, GSTT-1 by PCR, and HLA-DR15 levels.

DISEASE CHARACTERISTICS:

- Low or intermediate-1 risk myelodysplastic syndromes by International Prognostic
Scoring System (IPSS) criteria

- IPSS score < 1.5

- Requiring transfusion of 2 units of red blood cells at least once a month (four weeks
prior to accrual on study)

- High levels of endogenous epoetin alfa (i.e., > 200 mU/mL)

- Unlikely to respond to epoetin alfa, or has a documented clinical non-response to
epoetin alfa (at a dose of ≥ 40,000 U weekly) or darbepoetin alfa (at a dose >
200 mcg every other week) (i.e., < 2 g/dL increase in hemoglobin and no decrease
in transfusion requirements after at least 4 weeks of treatment)

- No chronic myelomonocytic leukemia

PATIENT CHARACTERISTICS:

- ECOG Performance Status of 0-2

- Liver enzymes (AST and ALT) and total bilirubin ≤ 2 times upper limit of normal

- Serum creatinine ≤ 2 times upper limits of normal

- No clinically significant anemia due to iron, B12, or folate deficiencies; autoimmune
or hereditary hemolysis; or gastrointestinal bleeding

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No other serious or poorly controlled medical condition that could be exacerbated by
or complicate compliance with study therapy

PRIOR CONCURRENT THERAPY:

- At least 4 weeks since prior treatment (including growth factors)

- No chronic use (> 2 weeks) of physiologic doses of a corticosteroid agent (dose
equivalent to > 10 mg/day of prednisone) within 28 days of the first day of study drug

- No concurrent use of another investigational agent

- No concurrent therapy with any cytotoxic drugs, steroids, or growth factors