A Phase 2 Trial of RAD001(Everolimus) in Low and Intermediate-1 Risk Myelodysplastic Syndrome
18 Years
N/A
Both
Myelodysplastic Syndromes
Trial Information
A Phase 2 Trial of RAD001(Everolimus) in Low and Intermediate-1 Risk Myelodysplastic Syndrome
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Number of Patients With Either a Major or Minor Erythroid Response(Hemoglobin Change From Baseline Measure)
Outcome Description:
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.
Outcome Time Frame:
2 years of treatment
Safety Issue:
No
Principal Investigator
Anjali Advani, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
CASE1905
NCT ID:
NCT00809185
Start Date:
November 2005
Completion Date:
March 2009
Related Keywords:
- Myelodysplastic Syndromes
- de novo myelodysplastic syndromes
- secondary myelodysplastic syndromes
- previously treated myelodysplastic syndromes
- Myelodysplastic Syndromes
- Preleukemia
Name | Location |
|---|---|
| Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center | Cleveland, Ohio 44195 |
