RAD001(Everolimus) in Treating Patients With Myelodysplastic Syndromes
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.
Other: laboratory biomarker analysis
Procedure: Bone marrow aspirate/biopsy
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 2 Trial of RAD001(Everolimus) in Low and Intermediate-1 Risk Myelodysplastic Syndrome|
- Number of Patients With Either a Major or Minor Erythroid Response(Hemoglobin Change From Baseline Measure) [ Time Frame: 2 years of treatment ] [ Designated as safety issue: No ]
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.
- Dose- and Non-dose-limiting Toxicities [ Time Frame: at end of one cycle (28 days) ] [ Designated as safety issue: Yes ]
- Laboratory Correlates (Cytotoxic T-cell Populations, S6K1 Levels, GSTT-1 Mutations, and Presence or Absence of HLA-DR15) [ Time Frame: at 2 years of treatment ] [ Designated as safety issue: No ]
- Bone Marrow Morphology and Cytogenetics Pre- and Post-therapy [ Time Frame: at 2 years of treatment ] [ Designated as safety issue: No ]
|Study Start Date:||November 2005|
|Study Completion Date:||March 2009|
|Primary Completion Date:||February 2009 (Final data collection date for primary outcome measure)|
- 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.
- 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.
|United States, Ohio|
|Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center|
|Cleveland, Ohio, United States, 44195|
|Study Chair:||Anjali Advani, MD||Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer Center|