Sorafenib in Myelodysplastic Syndrome

NCT00510289 | Terminated Phase 2 Results DMC

• 1 other identifier: Pro00008151
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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.

Conditions

Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic

Keywords

Sorafenib; Myelodysplastic Syndromes; MDS

Outcome Measures

Primary Outcomes (1)

• 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.

  During treatment - up to a maximum of 5 years

Secondary Outcomes (4)

• Number of Subjects Requiring Dose Reductions

  While on study drug, a maximum of 5 years

• Time to Progression

  5 years

• Overall Survival

  1 year from the last dose of study drug

• Change in Microvessel Density

  Measured before and after treatment

Study Arms (1)

all patients

EXPERIMENTAL

sorafenib

Drug: Sorafenib

Interventions

Sorafenib DRUG

400 mg twice a day until progression or unacceptable toxicity develops.

Also known as: Nexavar

all patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Duke University: lead
• Bayer: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

The limitations of our study include the small sample size, the poor toxicity profile and the lack of response.

Results Point of Contact

• Title: David Rizzieri, MD
• Organization: Duke University Medical Center

David.Rizzieri@duke.edu

919-668-1014

Study Officials

• David A Rizzieri, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2007
• First Posted: August 1, 2007
• Study Start: July 1, 2006
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: April 19, 2016
• Results First Posted: February 11, 2014

Record last verified: 2016-03

Locations

US (1)