RAD001(Everolimus) in Treating Patients With Myelodysplastic Syndromes

Case Comprehensive Cancer Center (Case CCC)

Status and phase

Terminated

Phase 2

Conditions

Myelodysplastic Syndromes

Treatments

Procedure: Bone marrow aspirate/biopsy

Drug: everolimus

Other: laboratory biomarker analysis

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00809185

CASE-CCF-8514 (Other Identifier)

P30CA043703 (U.S. NIH Grant/Contract)

CASE1905 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

7 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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