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A Phase 2 Trial of RAD001(Everolimus) in Low and Intermediate-1 Risk Myelodysplastic Syndrome

Phase 2
18 Years
Not Enrolling
Myelodysplastic Syndromes

Thank you

Trial Information

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.

Inclusion Criteria


- 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


- 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


- 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

- No concurrent use of another investigational agent

- No concurrent therapy with any cytotoxic drugs, steroids, or growth factors

Type of Study:


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:


Principal Investigator

Anjali Advani, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:




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



Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center Cleveland, Ohio  44195