RAD001(Everolimus) in Treating Patients With Myelodysplastic Syndromes

Phase 2

Terminated

Interventions: Drug: everolimus
Other: laboratory biomarker analysis
Procedure: Bone marrow aspirate/biopsy

Brief 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.

Detailed Description: 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.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
RAD001 (everolimus)	laboratory biomarker analysis	RAD001 (everolimus) at 10mg/day with Bone marrow aspirate/biopsy and other laboratory biomarker analysis
RAD001 (everolimus)	Bone marrow aspirate/biopsy	RAD001 (everolimus) at 10mg/day with Bone marrow aspirate/biopsy and other laboratory biomarker analysis
RAD001 (everolimus)	everolimus	RAD001 (everolimus) at 10mg/day with Bone marrow aspirate/biopsy and other laboratory biomarker analysis

Primary Outcome Measures

Name	Time	Method
Number of Patients With Either a Major or Minor Erythroid Response (Hemoglobin Change From Baseline Measure)	2 years of treatment	Major erythroid response: (1) For patients with a baseline hemoglobin less than 11 g/dL, a major erythroid response is defined as a \> 2 g/dL increase in hemoglobin from baseline; or (2) 100% decrease in red blood cell transfusion requirements. Minor erythroid response: (1) For patients with baseline hemoglobin less than 11 g/dL, a minor erythroid response is defined as an increase in hemoglobin greater than 1 g/dL but less than 2 g/dL from baseline; or (2) \> 50% decrease in red blood cell transfusion requirements.

Secondary Outcome Measures

Name	Time	Method
Number of Dose- and Non-dose-limiting Toxicities	at end of one cycle (28 days)	Number of Dose- and Non-dose-limiting Toxicities at the end of cycle 1 associated with RAD001 (see AE/SAE section for details).
Number of Participants With Bone Marrow Morphology and Cytogenetics Pre- and Post-therapy	at 2 years of treatment	Number of Participants with change in bone marrow morphology and cytogenetics