RAD001(Everolimus) in Treating Patients With Myelodysplastic Syndromes

This study has been terminated.
(slow accrual)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00809185
First received: December 16, 2008
Last updated: April 10, 2012
Last verified: April 2012
  Purpose

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: 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

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 ] [ 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.



Secondary Outcome Measures:
  • 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 ]

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)
Intervention Details:
    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:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00809185

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

No publications provided by Case Comprehensive Cancer Center

Additional 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, CASE-CCF-8514, CASE1905
Study First Received: December 16, 2008
Results First Received: January 20, 2012
Last Updated: April 10, 2012
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Disease
Pathologic Processes
Sirolimus
Everolimus
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 30, 2014