Myelodysplastic SyndromesPhase 2NCT00510289
Sorafenib in Myelodysplastic Syndrome
A Phase 2 study testing Sorafenib in people with Myelodysplastic Syndromes and Leukemia, Myelomonocytic, Chronic, run by Duke University at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the efficacy of sorafenib in patients with Myelodysplastic Syndrome (MDS). Eligible subjects will receive Sorafenib administered at 400mg orally twice a day, given on days 1-28 of a 28-day cycle. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic
- What is being tested?
- Sorafenib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2006to Jul 2011
- 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
Who may be able to join
- Patients must have a diagnosis of primary or therapy-related myelodysplastic syndrome or myelodysplastic/ myeloproliferative disorders as defined by the WHO
- Refractory anemia with excess blasts - 1 or 2
- Chronic myelomonocytic leukemia type 2
- Refractory anemia, refractory anemia with ringed sideroblasts, refractory cytopenia with multilineage dysplasia, refractory cytopenia with multilineage dysplasia with ringed sideroblasts, 5q- syndrome, myelodysplastic syndrome unclassified or chronic myelomonocytic leukemia type 1 if at least one of the following criteria is met: HgB < 10 g/dl, Platelets < 50,000/ul,ANC < 1,000 ul, Transfusion dependent defined as 2 transfusions within an 8 week period.
- Patients may have low, intermediate-1, intermediate-2 or high risk MDS or CMML.
- Patients are eligible without regard to prior treatment status except for allogenic bone marrow transplant.
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- Patients must be 18 years of age or older.
- Patient has an estimated or measured creatinine clearance ≥30 ml/min at study enrollment.
- AST, ALT, total bilirubin ≤ than 2.5 times the upper limit of normal.
- ECOG performance status of 0-2.
- Voluntary written informed consent before performance of any study-related procedure not part of normal medical care.
- Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control.
- Male subject agrees to use an acceptable method for contraception for the duration of the study therapy and for 2 weeks after study completion.
Who cannot join
- Female subject is pregnant or lactating. Confirmation that the subject is not pregnant must be established by a negative serum B-human chorionic gonadotropin (B-hCG) pregnancy test result within 2 weeks of enrollment. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
- Patient has received other investigational drugs for this disease within 14 days of enrollment
- No growth factor support with erythropoietin, GCSF, or GMCSF within 28 days of enrolling in the study.
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
- Patients with another malignancy within the last one year (from documentation of remission) other than basal or squamous cell skin cancer or CIS of the cervix.
- Patients who underwent allogeneic stem cell transplant will be excluded.
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- History of leukemia (having more than 20% blasts in blood or marrow)
- Current treatment with coumadin, heparin and its derivatives.
- Major surgery (including needle biopsy of visceral organs) for 1-month prior to study and fully recovered. In addition, no placement of a subcutaneous or tunneled venous access device for 3 days prior to study and adequately healed.
- Significant cardiac or vascular events within 6 months: acute MI, unstable angina, severe peripheral vascular disease (ischemic pain at rest class 3 or worse, non-healing ulcers/wounds, congestive heart failure (NHYA class ≥ 2), uncontrolled cardiac arrhythmias, and disseminated intravascular coagulation.
- No use of hematopoetic growth factors within 4 weeks of starting sorafenib.
- Known severe hypersensitivity to Sorafenib or any component of the formulation.
- Caution should be exercised with the concomitant use of other CYP3A4 inducers, such as rifampin, St. John's Wort, phenytoin, phenobarbital and dexamethasone.
- Uncontrolled hypertension with a systolic blood pressure greater than 160 or a diastolic blood pressure greater than 100 despite treatment.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: Phase II Trial of Sorafenib in Patients With Myelodysplastic Syndrome
The purpose of this study is to evaluate the efficacy of sorafenib in patients with Myelodysplastic Syndrome (MDS). Eligible subjects will receive Sorafenib administered at 400mg orally twice a day, given on days 1-28 of a 28-day cycle. Patients will be evaluated for hematological response after 2 cycles and then every 3 cycles thereafter for a maximum of 5 years from study entry. If a patient achieves a complete response they may receive an additional 6 cycles of therapy beyond documentation of complete response unless unacceptable toxicity occurs. For patients with partial response, hematological improvement or stable disease they will continue treatment until relapse, progression of disease, or unacceptable toxicity occurs.
- Being tested
- Sorafenib
- Keywords
- Sorafenib, Myelodysplastic Syndromes, MDS
- Medical subject headings
- Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SorafenibDrug
Also called Nexavar
400 mg twice a day until progression or unacceptable toxicity develops.
| Study group | Role | What they receive |
|---|---|---|
| all patients | Experimental | sorafenib Receives: Drug: Sorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects Achieving Hematological Response
Hematological response is defined as the number of subjects who achieve either a complete response (CR), Partial response (PR) or Hematologic improvement.(HI). HI is defined as peripheral blood counts with hemoglobin ≥11 g/dL, absolute neutrophil count ≥1x10(9)/L and platelet count ≥100x10(9)/L, and normal bone marrow morphology with no evidence of dysplasia or blasts. CR is defined as the disappearance of all signs and symptoms related to disease, along with HI. PR is defined as fulfilling the criteria for CR in the peripheral blood but blasts decreasing by 50% or more in the bone marrow or to a less advanced WHO classification pretreatment.
Measured: During treatment - up to a maximum of 5 years
Secondary outcomes (4)
Number of Subjects Requiring Dose Reductions
The number of subjects who took study drug for more than 1 cycle and required a dose reduction down to the next dose level.
Measured: While on study drug, a maximum of 5 years
Time to Progression
Time to progression will be defined as the number of months between on-study and the date of progression or death, whichever comes first, in subjects who took study drug for at least cycle 1.
Measured: 5 years
Overall Survival
Overall Survival is defined as the number of months from enrollment onto the study until death from any cause in subjects who took study drug for at least cycle 1.
Measured: 1 year from the last dose of study drug
Change in Microvessel Density
Microvessel density will be measured before and after treatment, and the distribution of change across time will be summarized with descriptive statistics.
Measured: Measured before and after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2007 (estimated)
- Study startJul 2006
- Primary completionJul 2011
- Study completionJul 2011
Why it stopped: Early closure of study due to poor response
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.
- Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe 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
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Sponsor
- Investigators
- David A Rizzieri, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00510289
- Sponsor's protocol ID
- Pro00008151
- Status last verified
- Mar 2016
- First submitted
- 30 Jul 2007
- Last updated
- 19 Apr 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Sorafenib in Patients With Myelodysplastic Syndrome
- ClinicalTrials.gov ID
- NCT00510289
- Acronym / sponsor ID
- Pro00008151
- Keywords
- Sorafenib, Myelodysplastic Syndromes, MDS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Early closure of study due to poor response
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- Jul 2006
- Primary completion
- Jul 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 1 Aug 2007 (estimated)
- Results
- Posted 11 Feb 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the efficacy of sorafenib in patients with Myelodysplastic Syndrome (MDS). Eligible subjects will receive Sorafenib administered at 400mg orally twice a day, given on days 1-28 of a 28-day cycle. Patients will be evaluated for hematological response after 2 cycles and then every 3 cycles thereafter for a maximum of 5 years from study entry. If a patient achieves a complete response they may receive an additional 6 cycles of therapy beyond documentation of complete response unless unacceptable toxicity occurs. For patients with partial response, hematological improvement or stable disease they will continue treatment until relapse, progression of disease, or unacceptable toxicity occurs.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| all patients | Experimental | Drug: Sorafenibsorafenib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients must have a diagnosis of primary or therapy-related myelodysplastic syndrome or myelodysplastic/ myeloproliferative disorders as defined by the WHO
- Patients may have low, intermediate-1, intermediate-2 or high risk MDS or CMML.
- Patients are eligible without regard to prior treatment status except for allogenic bone marrow transplant.
- Patients must be 18 years of age or older.
- Patient has an estimated or measured creatinine clearance ≥30 ml/min at study enrollment.
Key exclusion criteria (14 listed)
- Female subject is pregnant or lactating. Confirmation that the subject is not pregnant must be established by a negative serum B-human chorionic gonadotropin (B-hCG) pregnancy test result within 2 weeks of enrollment. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
- Patient has received other investigational drugs for this disease within 14 days of enrollment
- No growth factor support with erythropoietin, GCSF, or GMCSF within 28 days of enrolling in the study.
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
- Patients with another malignancy within the last one year (from documentation of remission) other than basal or squamous cell skin cancer or CIS of the cervix.
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 |
|---|---|---|
| SorafenibAlso: Nexavar400 mg twice a day until progression or unacceptable toxicity develops. | Drug | all patients |
Primary outcome
Number of Subjects Achieving Hematological Response
Time frame: During treatment - up to a maximum of 5 years
Hematological response is defined as the number of subjects who achieve either a complete response (CR), Partial response (PR) or Hematologic improvement.(HI). HI is defined as peripheral blood counts with hemoglobin ≥11 g/dL, absolute neutrophil count ≥1x10(9)/L and platelet count ≥100x10(9)/L, and normal bone marrow morphology with no evidence of dysplasia or blasts. CR is defined as the disappearance of all signs and symptoms related to disease, along with HI. PR is defined as fulfilling the criteria for CR in the peripheral blood but blasts decreasing by 50% or more in the bone marrow or to a less advanced WHO classification pretreatment.
4 secondary outcomes
Number of Subjects Requiring Dose Reductions
Time frame: While on study drug, a maximum of 5 years
Time to Progression
Time frame: 5 years
Overall Survival
Time frame: 1 year from the last dose of study drug
Change in Microvessel Density
Time frame: Measured before and after treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
David A Rizzieri, MD principal investigator
Duke University
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 Sorafenib in people with Myelodysplastic Syndromes and Leukemia, Myelomonocytic, Chronic, run by Duke University 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?
The sponsor lists 13 inclusion and 14 exclusion criteria. 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 19 Apr 2016. 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 11 Feb 2014). 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 Subjects Achieving Hematological Response (time frame: During treatment - up to a maximum of 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Apr 2016.