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RAD001(Everolimus) in Treating Patients With Myelodysplastic Syndromes

Primary Purpose

Myelodysplastic Syndromes

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
everolimus
laboratory biomarker analysis
Bone marrow aspirate/biopsy
Sponsored by
Case Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myelodysplastic Syndromes focused on measuring de novo myelodysplastic syndromes, secondary myelodysplastic syndromes, previously treated myelodysplastic syndromes

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

RAD001 (everolimus)

Arm Description

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

Outcomes

Primary Outcome Measures

Number of Patients With Either a Major or Minor Erythroid Response (Hemoglobin Change From Baseline Measure)
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

Number of Dose- and Non-dose-limiting Toxicities
Number of Dose- and Non-dose-limiting Toxicities at the end of cycle 1 associated with RAD001 (see AE/SAE section for details).
Number of Participants With Bone Marrow Morphology and Cytogenetics Pre- and Post-therapy
Number of Participants with change in bone marrow morphology and cytogenetics

Full Information

First Posted
December 16, 2008
Last Updated
February 25, 2019
Sponsor
Case Comprehensive Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00809185
Brief Title
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

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Terminated
Why Stopped
slow accrual
Study Start Date
November 2005 (undefined)
Primary Completion Date
February 2009 (Actual)
Study Completion Date
March 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Case Comprehensive Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndromes
Keywords
de novo myelodysplastic syndromes, secondary myelodysplastic syndromes, previously treated myelodysplastic syndromes

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
RAD001 (everolimus)
Arm Type
Experimental
Arm Description
RAD001 (everolimus) at 10mg/day with Bone marrow aspirate/biopsy and other laboratory biomarker analysis
Intervention Type
Drug
Intervention Name(s)
everolimus
Other Intervention Name(s)
RAD001
Intervention Description
Patients will receive monotherapy with RAD001(everolimus)for 21 days within the 28 day cycle.
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
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
Procedure
Intervention Name(s)
Bone marrow aspirate/biopsy
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Patients With Either a Major or Minor Erythroid Response (Hemoglobin Change From Baseline Measure)
Description
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.
Time Frame
2 years of treatment
Secondary Outcome Measure Information:
Title
Number of Dose- and Non-dose-limiting Toxicities
Description
Number of Dose- and Non-dose-limiting Toxicities at the end of cycle 1 associated with RAD001 (see AE/SAE section for details).
Time Frame
at end of one cycle (28 days)
Title
Number of Participants With Bone Marrow Morphology and Cytogenetics Pre- and Post-therapy
Description
Number of Participants with change in bone marrow morphology and cytogenetics
Time Frame
at 2 years of treatment
Other Pre-specified Outcome Measures:
Title
Laboratory Correlates (Cytotoxic T-cell Populations, S6K1 Levels, GSTT-1 Mutations, and Presence or Absence of HLA-DR15)
Description
T-cell populations in patients pre- and post-treatment
Time Frame
at 2 years of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anjali Advani, MD
Organizational Affiliation
Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
24332215
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.
Results Reference
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RAD001(Everolimus) in Treating Patients With Myelodysplastic Syndromes

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