Myelodysplastic SyndromesPhase 2NCT00809185
RAD001(Everolimus) in Treating Patients With Myelodysplastic Syndromes
A Phase 2 study testing everolimus, laboratory biomarker analysis and Bone marrow aspirate/biopsy in people with Myelodysplastic Syndromes, run by Case Comprehensive Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndromes
- What is being tested?
- everolimus, laboratory biomarker analysis and Bone marrow aspirate/biopsy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2005to Mar 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
1 site in 1 country.
United States1 site
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, 44195
About this study
Official title: A Phase 2 Trial of RAD001(Everolimus) in Low and Intermediate-1 Risk Myelodysplastic Syndrome
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.
Read the 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
- Being tested
- everolimus, laboratory biomarker analysis, Bone marrow aspirate/biopsy
- Keywords
- de novo myelodysplastic syndromes, secondary myelodysplastic syndromes, previously treated myelodysplastic syndromes
- Medical subject headings
- Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
everolimusDrug
Also called RAD001
Patients will receive monotherapy with RAD001(everolimus)for 21 days within the 28 day cycle.
laboratory biomarker analysisOther
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/biopsyProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| RAD001 (everolimus) | Experimental | RAD001 (everolimus) at 10mg/day with Bone marrow aspirate/biopsy and other laboratory biomarker analysis Receives: Drug: everolimus; Other: laboratory biomarker analysis; Procedure: Bone marrow aspirate/biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 years of treatment
Secondary outcomes (2)
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).
Measured: at end of one cycle (28 days)
Number of Participants With Bone Marrow Morphology and Cytogenetics Pre- and Post-therapy
Number of Participants with change in bone marrow morphology and cytogenetics
Measured: at 2 years of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2008 (estimated)
- Study startNov 2005
- Primary completionFeb 2009
- Study completionMar 2009
Why it stopped: slow accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
- More trials run by Case Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Case Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Anjali Advani, MD, Study chair, Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00809185
- Sponsor's protocol ID
- CASE1905
- Other IDs
- P30CA043703, CASE-CCF-8514, CASE1905
- Status last verified
- Feb 2019
- First submitted
- 16 Dec 2008
- Last updated
- 7 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 24332215
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Trial of RAD001(Everolimus) in Low and Intermediate-1 Risk Myelodysplastic Syndrome
- ClinicalTrials.gov ID
- NCT00809185
- Acronym / sponsor ID
- CASE1905
- Conditions
- Myelodysplastic Syndromes
- Keywords
- de novo myelodysplastic syndromes, secondary myelodysplastic syndromes, previously treated myelodysplastic syndromes
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: slow accrual
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Case Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Nov 2005
- Primary completion
- Feb 2009 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 17 Dec 2008 (estimated)
- Results
- Posted 4 May 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RAD001 (everolimus) | Experimental | Drug: everolimus, Other: laboratory biomarker analysis, Procedure: Bone marrow aspirate/biopsyRAD001 (everolimus) at 10mg/day with Bone marrow aspirate/biopsy and other laboratory biomarker analysis |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| everolimusAlso: RAD001Patients will receive monotherapy with RAD001(everolimus)for 21 days within the 28 day cycle. | Drug | RAD001 (everolimus) |
| laboratory biomarker analysisLaboratory 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. | Other | RAD001 (everolimus) |
| Bone marrow aspirate/biopsyBone 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. | Procedure or surgery | RAD001 (everolimus) |
Primary outcome
Number of Patients With Either a Major or Minor Erythroid Response (Hemoglobin Change From Baseline Measure)
Time frame: 2 years of treatment
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.
2 secondary outcomes
Number of Dose- and Non-dose-limiting Toxicities
Time frame: at end of one cycle (28 days)
Number of Participants With Bone Marrow Morphology and Cytogenetics Pre- and Post-therapy
Time frame: at 2 years of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24332215Advani 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anjali Advani, MD study chair
Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing everolimus, laboratory biomarker analysis and Bone marrow aspirate/biopsy in people with Myelodysplastic Syndromes, run by Case Comprehensive Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 7 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 May 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients With Either a Major or Minor Erythroid Response (Hemoglobin Change From Baseline Measure) (time frame: 2 years of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00809185, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Mar 2019.