rad001(everolimus) in treating patients with myelodysplastic syndromes

Conditions: Myelodysplastic Syndromes

Summary: rationale: rad001(everolimus) may stop the growth of cancer cells by blocking some of the enzymes needed for their growth and by blocking blood flow to the cancer. purpose: this phase ii trial is studying how well rad001(everolimus) works 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.

Eligibility criteria:
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

Keywords: de novo myelodysplastic syndromes secondary myelodysplastic syndromes previously treated myelodysplastic syndromes