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)|
Experimental: RAD001 (everolimus)
RAD001 (everolimus) at 10mg/day with Bone marrow aspirate/biopsy and other laboratory biomarker analysis
Patients will receive monotherapy with RAD001(everolimus)for 21 days within the 28 day cycle.
Other Name: RAD001Other: laboratory biomarker analysis
Laboratory correlates (cytotoxic t cell populations, S6K1 levels, GSTT-1 mutations, and the presence or absence of HLA-DR15) will be assessed to see if any of these correlates correspond to response.Procedure: Bone marrow aspirate/biopsy
Bone marrow aspirate and biopsy with cytogenetics should be obtained within 4 weeks prior to starting drug and at week 33. A bone marrow aspirate and biopsy should also be obtained for patients going off study prior to week 33 (including cytogenetics). The percentage of blasts on the aspirate should be used to determine the IPSS score.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00809185
|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|