We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov Menu

RAD001(Everolimus) in Treating Patients With Myelodysplastic Syndromes

This study has been terminated.
(slow accrual)
ClinicalTrials.gov Identifier:
First Posted: December 17, 2008
Last Update Posted: October 19, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Case Comprehensive Cancer Center

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.

Condition Intervention Phase
Myelodysplastic Syndromes Drug: everolimus Other: laboratory biomarker analysis Procedure: Bone marrow aspirate/biopsy Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Trial of RAD001(Everolimus) in Low and Intermediate-1 Risk Myelodysplastic Syndrome

Resource links provided by NLM:

Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • Number of Patients With Either a Major or Minor Erythroid Response(Hemoglobin Change From Baseline Measure) [ Time Frame: 2 years of treatment ]

    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.

Secondary Outcome Measures:
  • Dose- and Non-dose-limiting Toxicities [ Time Frame: at end of one cycle (28 days) ]
  • 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 ]
  • Bone Marrow Morphology and Cytogenetics Pre- and Post-therapy [ Time Frame: at 2 years of treatment ]

Enrollment: 7
Study Start Date: November 2005
Study Completion Date: March 2009
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RAD001 (everolimus)
RAD001 (everolimus) at 10mg/day with Bone marrow aspirate/biopsy and other laboratory biomarker analysis
Drug: everolimus
Patients will receive monotherapy with RAD001(everolimus)for 21 days within the 28 day cycle.
Other Name: RAD001
Other: 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.

Detailed Description:



  • 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.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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 drug
  • No concurrent use of another investigational agent
  • No concurrent therapy with any cytotoxic drugs, steroids, or growth factors
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00809185

United States, Ohio
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
Case Comprehensive Cancer Center
National Cancer Institute (NCI)
Study Chair: Anjali Advani, MD Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer Center
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00809185     History of Changes
Other Study ID Numbers: CASE1905
P30CA043703 ( U.S. NIH Grant/Contract )
CASE-CCF-8514 ( Other Identifier: Cleveland Clinic IRB )
CASE1905 ( Other Identifier: Case Comprehensive Cancer Center )
First Submitted: December 16, 2008
First Posted: December 17, 2008
Results First Submitted: January 20, 2012
Results First Posted: May 4, 2012
Last Update Posted: October 19, 2015
Last Verified: September 2015

Keywords provided by Case Comprehensive Cancer Center:
de novo myelodysplastic syndromes
secondary myelodysplastic syndromes
previously treated myelodysplastic syndromes

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents