Clinical trial NCT00510289: Sorafenib in Myelodysplastic Syndrome
Official title: Phase II Trial of Sorafenib in Patients With Myelodysplastic Syndrome
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Myelodysplastic Syndromes
Leukemia, Myelomonocytic, Chronic
Keywords: Sorafenib
Myelodysplastic Syndromes
MDS
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2007-08-01
Enrollment: 19
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: 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.


Eligibility criteria: Inclusion Criteria:

* 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.
* 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.

Exclusion Criteria:

* 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.
* 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.

Primary outcomes:
measure: Number of Subjects Achieving Hematological Response
timeFrame: During treatment - up to a maximum of 5 years
Secondary outcomes:
measure: Number of Subjects Requiring Dose Reductions
timeFrame: While on study drug, a maximum of 5 years
measure: Time to Progression
timeFrame: 5 years
measure: Overall Survival
timeFrame: 1 year from the last dose of study drug
measure: Change in Microvessel Density
timeFrame: Measured before and after treatment
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: David A Rizzieri, MD
role: PRINCIPAL_INVESTIGATOR
References: