Phase II, Open Label, Single Arm Study of SAR302503 In Myelofibrosis Patients Previously Treated With Ruxolitinib

• Status: Completed
• Trial end date: 2014-04-01
• Target enrollment: 0
• Participant gender: All

Summary

Primary Objective:

• To evaluate the efficacy of once daily dose of SAR302503 in subjects previously treated with ruxolitinib and with a current diagnosis of intermediate-1 with symptoms, Intermediate-2 or high-risk primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (Post-PV MF), or post-essential thrombocythemia myelofibrosis (Post-ET MF) based on the reduction of spleen volume at the end of 6 treatment cycles;

Secondary Objectives:

• To evaluate the effect of SAR302503 on Myelofibrosis (MF) associated symptoms as measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF) diary

• To evaluate the durability of splenic response

• To evaluate the splenic response to SAR302503 by palpation at the end of Cycle 6

• To evaluate the splenic response to SAR302503 at the end of Cycle 3

• To evaluate the effect of SAR302503 on the Janus kinase 2 (JAK2) V617F allele burden

• To evaluate the safety and tolerability of SAR302503 in this population

• To evaluate plasma concentrations of SAR302503 for population PK analysis, if warranted

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sanofi

Criteria

Inclusion criteria:

• Diagnosis of PMF or Post-PV MF or Post-ET MF, according to the 2008 World Health Organization and IWG-MRT response criteria

• Subjects who previously received Ruxolitinib treatment for PMF or Post-PV MF or Post-ET MF or PV or ET for at least 14 days (exposure of <14 days is allowed for subjects who discontinued Ruxolitinib due to intolerability or allergy) and discontinued the treatment for at least 14 days prior to the first dose of SAR302503

• MF classified as Intermediate-1 with symptoms, Intermediate-2 or high-risk by Dynamic International Prognostic Scoring System (Passamonti et al., Blood 2010)

• Spleen ≥5 cm below costal margin as measured by palpation

• Male and female subjects ≥18 years of age

• Signed written informed consent

Exclusion criteria:

• Splenectomy

• Eastern Cooperative Oncology Group (ECOG) performance status of >2 before the first dose of SAR302503 at Cycle 1 Day1

• The following laboratory values within 14 days prior to the initiation of SAR302503:

• Absolute Neutrophil Count (ANC) <1.0 x 10exp9/L

• Platelet count <50 x 10exp9/L

• Serum creatinine >1.5 x Upper limit of normal (ULN)

• Serum amylase and lipase >1.5 x ULN

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2.5 x ULN

• Total bilirubin ≥3.0 x ULN

• Subjects with total bilirubin between 1.5-3.0 x ULN must be excluded if the direct bilirubin fraction is ≥25% of the total

• Subjects with known active (acute or chronic) Hepatitis A, B, or C; and Hepatitis B and C carriers

• Prior history of chronic liver disease (eg, chronic alcoholic liver disease, autoimmune hepatitis, sclerosing cholangitis, primary biliary cirrhosis, hemachromatosis, non-alcoholic steatohepatitis [NASH])

• Subjects with any other prior malignancies are not eligible, except for the following:

adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which subject has been disease-free for at least 5 years

• Any chemotherapy, immunomodulatory drug therapy (eg, thalidomide, interferon-alpha), Anagrelide, immunosuppressive therapy, corticosteroids >10 mg/day prednisone or equivalent, or growth factor treatment (eg, erythropoietin), or hormones (eg, androgens, danazol) within 14 days prior to initiation of SAR302503; darbepoetin use within 28 days prior to initiation of SAR302503.The only chemotherapy allowed will be hydroxyurea within 1 day prior to initiation of SAR302503

• Uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack, or pulmonary embolism within 3 months prior to initiation of SAR302503

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.