RAD001(Everolimus) in Treating Patients With Myelodysplastic Syndromes

NCT ID: NCT00809185

Last Updated: 2019-03-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-11-30
• Study Completion Date: 2009-03-31

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.

Conditions

Myelodysplastic Syndromes

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

RAD001 (everolimus)

RAD001 (everolimus) at 10mg/day with Bone marrow aspirate/biopsy and other laboratory biomarker analysis

Group Type: EXPERIMENTAL

everolimus

Intervention Type: DRUG

Patients will receive monotherapy with RAD001(everolimus)for 21 days within the 28 day cycle.

laboratory biomarker analysis

Intervention Type: OTHER

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.

Bone marrow aspirate/biopsy

Intervention Type: PROCEDURE

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.

Interventions

everolimus

Patients will receive monotherapy with RAD001(everolimus)for 21 days within the 28 day cycle.

Intervention Type: DRUG

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.

Intervention Type: OTHER

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.

Intervention Type: PROCEDURE

Other Intervention Names

RAD001

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Case Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anjali Advani, MD

Role: STUDY_CHAIR

Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer Center

Locations

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 24332215 (View on PubMed)

Other Identifiers

P30CA043703

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CASE-CCF-8514

Identifier Type: OTHER

Identifier Source: secondary_id

CASE1905

Identifier Type: OTHER

Identifier Source: secondary_id

CASE1905

Identifier Type: -

Identifier Source: org_study_id