phase ii, open label, single arm study of sar302503 in myelofibrosis patients previously treated with ruxolitinib

Conditions: Hematopoietic Neoplasm

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

the expected duration of the treatment in this study is approximately 8 months, based on a maximum 28-day screening period, followed by a 6-month (6-cycle) treatment period, and an eot visit for subjects who will not continue the treatment after completing the 6 cycles of sar302503, or discontinue the treatment early for any reasons as well as a follow-up visit which should occur 30 days after the last administration of sar302503. patients who continue to benefit clinically will be allowed to remain on study medication beyond the 6-month treatment period until the occurrence of disease progression or unacceptable toxicity.

Eligibility 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.