Hematopoietic neoplasm MedDRA version: 20.1 Level: LLT Classification code 10018864 Term: Haematopoietic neoplasm NOS System Organ Class: 100000004864
Conditions
Sponsors
Sanofi-aventis Recherche & Développement
Eligibility
Sex/Gender
All
Inclusion 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 and discontinued the treatment for at least 30 days prior to study entry MF classified as high-risk or intermediate-risk level 2 (IWG-MRT response criteria IPSS assess myelofibrosis score, Cervantes, et al, Blood 2009) Spleen =5 cm below costal margin as measured by palpation Male and female subjects =18 years of age Signed written informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Splenectomy Eastern Cooperative Oncology Group (ECOG) performance status of >2 at study entry The following laboratory values within 14 days prior to the initiation of SAR302503: Absolute Neutrophil Count (ANC) 1.5 x Upper limit of normal (ULN) Serum amylase and lipase >1.5 x ULN Direct bilirubin >2.0 x ULN Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 x ULN; higher values (ie, >5 x ULN) are allowed if clinically compatible with hepatic extramedullary hematopoiesis 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 (eg, hydroxyurea), 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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Response Rate (RR), defined as the proportion of subjects who have a =35% reduction from baseline in volume of spleen at the end of Cycle 6 as measured by Magnetic Resonance Imaging (MRI) (or CT scan in subjects with contraindications for MRI) ;Main Objective: To evaluate the efficacy of once daily dose of SAR302503 in subjects previously treated with ruxolitinib and with a current diagnosis of 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 Objective: 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 through the first 6 treatment cycles 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 ;Timepoint(s) of evaluation of this end point: 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Symptom Response Rate (SRR): Proportion of subjects with a =50% reduction from baseline to the end of Cycle 6 in the total symptom score using the modified MFSAF - Duration of spleen response, measured by MRI (or CT scan in subjects with contraindications for MRI) - Proportion of subjects with a =50% reduction in length of spleen by palpation from baseline at the end of Cycle 6 - Response Rate by Cycle 6 (RR6), defined as the proportion of subjects who have a =35% reduction from baseline in volume of spleen at any time up to Cycle 6 as measured by MRI (or CT scan in subjects with contraindications for MRI) - The effect of SAR302503 on the JAK2V617F allele burden - Safety, as assessed by clinical, laboratory, ECG, and vital sign events; graded by the NCI CTCAE v4.03 - Plasma concentrations of SAR302503 ; Timepoint(s) of evaluation of this end point: - For the 4 first secondary end points: 6 months - The effect of SAR302503 on the JAK2V617F allele burden: 2 years - Safety, as assessed by clinical, laboratory, ECG, and vital sign events; graded by the NCI CTCAE v4.03: approx 5 years Plasma concentrations of SAR302503: 4 years | — |
Countries
Austria, Belgium, Germany, Italy, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactMedical Information
Sanofi-aventis Recherche & Développement
Outcome results
None listed