Everolimus in Treating Patients With Myelodysplastic Syndromes - Full Text View

Sponsors and Collaborators:	Case Comprehensive Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00809185

Purpose

RATIONALE: 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 everolimus works in treating patients with myelodysplastic syndromes.

Condition	Intervention	Phase
Myelodysplastic Syndromes	Drug: everolimus Genetic: polymerase chain reaction Other: flow cytometry Other: laboratory biomarker analysis	Phase II

MedlinePlus related topics: Cancer

Drug Information available for: Everolimus

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Phase 2 Trial of RAD001 in Low and Intermediate-1 Risk Myelodysplastic Syndrome

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Response [ Designated as safety issue: No ]

Secondary Outcome Measures:

Dose- and non-dose-limiting toxicities [ Designated as safety issue: Yes ]
Laboratory correlates (cytotoxic T-cell populations, S6K1 levels, GSTT-1 mutations, and presence or absence of HLA-DR15) [ Designated as safety issue: No ]
Bone marrow morphology and cytogenetics pre- and post-therapy [ Designated as safety issue: No ]

Estimated Enrollment:	33
Study Start Date:	November 2005
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the clinical activity (improvement in erythroid response and/or improvement in other cytopenias, bone marrow morphology/cytogenetics) of 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 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 everolimus.

OUTLINE: Patients receive oral 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 lnternational 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

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

Sponsors and Collaborators

Case Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Anjali Advani, MD

The Cleveland Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Cleveland Clinic Taussig Cancer Center ( Anjali Advani )
Study ID Numbers:	CDR0000446813, CASE-CCF-8514, CASE-CCF-1905, NOVARTIS-CASE-CCF-8514
Study First Received:	December 16, 2008
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00809185 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

de novo myelodysplastic syndromes
secondary myelodysplastic syndromes
previously treated myelodysplastic syndromes

Study placed in the following topic categories:

Everolimus
Preleukemia
Immunologic Factors
Precancerous Conditions
Hematologic Diseases

Myelodysplastic Syndromes
Neoplasm Metastasis
Bone Marrow Diseases
Immunosuppressive Agents

Additional relevant MeSH terms:

Everolimus
Disease
Precancerous Conditions
Immunologic Factors
Hematologic Diseases
Myelodysplastic Syndromes
Physiological Effects of Drugs

Immunosuppressive Agents
Pharmacologic Actions
Preleukemia
Neoplasms
Pathologic Processes
Syndrome
Bone Marrow Diseases

ClinicalTrials.gov processed this record on May 07, 2009