Clinical trial NCT00809185: RAD001(Everolimus) in Treating Patients With Myelodysplastic Syndromes
Official title: A Phase 2 Trial of RAD001(Everolimus) in Low and Intermediate-1 Risk Myelodysplastic Syndrome
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Myelodysplastic Syndromes
Keywords: de novo myelodysplastic syndromes
secondary myelodysplastic syndromes
previously treated myelodysplastic syndromes
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-12-17
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Number of Patients With Either a Major or Minor Erythroid Response (Hemoglobin Change From Baseline Measure)
timeFrame: 2 years of treatment
Secondary outcomes:
measure: Number of Dose- and Non-dose-limiting Toxicities
timeFrame: at end of one cycle (28 days)
measure: Number of Participants With Bone Marrow Morphology and Cytogenetics Pre- and Post-therapy
timeFrame: at 2 years of treatment
Other outcomes:
measure: Laboratory Correlates (Cytotoxic T-cell Populations, S6K1 Levels, GSTT-1 Mutations, and Presence or Absence of HLA-DR15)
timeFrame: at 2 years of treatment
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer Center
name: Anjali Advani, MD
role: STUDY_CHAIR
References:
citation: Advani AS, Mahfouz RZ, Maciejewski J, Rybicki L, Sekeres M, Tripp B, Kalaycio M, Bates J, Saunthararajah Y. Ribosomal S6 kinase and AKT phosphorylation as pharmacodynamic biomarkers in patients with myelodysplastic syndrome treated with RAD001. Clin Lymphoma Myeloma Leuk. 2014 Apr;14(2):172-177.e1. doi: 10.1016/j.clml.2013.10.001. Epub 2013 Nov 11.