A Phase 2 Trial of RAD001(Everolimus) in Low and Intermediate-1 Risk Myelodysplastic Syndrome
- 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
- 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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of Patients With Either a Major or Minor Erythroid Response(Hemoglobin Change From Baseline Measure)
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.
2 years of treatment
Anjali Advani, MD
Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer Center
United States: Food and Drug Administration
|Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center||Cleveland, Ohio 44195|