Phase II, Open Label, Single Arm Study of SAR302503 In Myelofibrosis Patients Previously Treated With Ruxolitinib
- Conditions
- Hematopoietic Neoplasm
- Interventions
- Drug: SAR302503
- Registration Number
- NCT01523171
- Lead Sponsor
- Sanofi
- Brief 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
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 97
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description SAR302503 400 mg SAR302503 once daily in consecutive 28-day cycles, flexible dosing regimen (the starting dose is 400mg/day), orally, empty stomach, approximately same time each day
- Primary Outcome Measures
Name Time Method 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) 6 months
- Secondary Outcome Measures
Name Time Method Percent change of spleen volume at the end of Cycles 3 and 6 from baseline as measured by MRI (or CT scan in subjects with contraindications for MRI) 6 months Duration of spleen response, measured by MRI (or CT scan in subjects with contraindications for MRI) 6 months Safety, as assessed by clinical, laboratory, ECG, and vital sign events; graded by the NCI CTCAE v4.03 approximately 5 years 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 6 months Proportion of subjects with a ≥50% reduction in length of spleen by palpation from baseline at the end of Cycle 6 6 months Response Rate at the end of Cycle 3, defined as the proportion of subjects who have a ≥35% reduction from baseline in volume of spleen at the end of Cycle 3 as measured by MRI (or CT scan in subjects with contraindications for MRI) 6 months Plasma concentrations of SAR302503 4 months The effect of SAR302503 on the JAK2V617F allele burden 2 years
Trial Locations
- Locations (42)
Investigational Site Number 840003
🇺🇸San Francisco, California, United States
Investigational Site Number 840005
🇺🇸Atlanta, Georgia, United States
Investigational Site Number 840004
🇺🇸San Francisco, California, United States
Investigational Site Number 840014
🇺🇸Chicago, Illinois, United States
Investigational Site Number 840001
🇺🇸Kansas City, Kansas, United States
Investigational Site Number 840017
🇺🇸Baltimore, Maryland, United States
Investigational Site Number 840009
🇺🇸New York, New York, United States
Investigational Site Number 840013
🇺🇸Baltimore, Maryland, United States
Investigational Site Number 840022
🇺🇸Cleveland, Ohio, United States
Investigational Site Number 840018
🇺🇸New York, New York, United States
Investigational Site Number 840019
🇺🇸Middletown, Ohio, United States
Investigational Site Number 380003
🇮🇹Varese, Italy
Investigational Site Number 840002
🇺🇸Houston, Texas, United States
Investigational Site Number 840015
🇺🇸Salt Lake City, Utah, United States
Investigational Site Number 528002
🇳🇱Amsterdam, Netherlands
Investigational Site Number 040002
🇦🇹Salzburg, Austria
Investigational Site Number 040001
🇦🇹Wien, Austria
Investigational Site Number 124001
🇨🇦Toronto, Canada
Investigational Site Number 250001
🇫🇷Marseille, France
Investigational Site Number 250003
🇫🇷Nimes Cedex 9, France
Investigational Site Number 250002
🇫🇷Paris Cedex 10, France
Investigational Site Number 250006
🇫🇷Paris Cedex 12, France
Investigational Site Number 250004
🇫🇷Toulouse, France
Investigational Site Number 276007
🇩🇪Leipzig, Germany
Investigational Site Number 276006
🇩🇪Magdeburg, Germany
Investigational Site Number 276001
🇩🇪Mannheim, Germany
Investigational Site Number 276005
🇩🇪Ulm, Germany
Investigational Site Number 380001
🇮🇹Milano, Italy
Investigational Site Number 380002
🇮🇹Roma, Italy
Investigational Site Number 380004
🇮🇹Firenze, Italy
Investigational Site Number 528003
🇳🇱Maastricht, Netherlands
Investigational Site Number 724001
🇪🇸Barcelona, Spain
Investigational Site Number 724002
🇪🇸Salamanca, Spain
Investigational Site Number 724003
🇪🇸Majadahonda, Spain
Investigational Site Number 826001
🇬🇧London, United Kingdom
Investigational Site Number 276003
🇩🇪Frankfurt Am Main, Germany
Investigational Site Number 528001
🇳🇱Nijmegen, Netherlands
Investigational Site Number 056003
🇧🇪Leuven, Belgium
Investigational Site Number 840007
🇺🇸Phoenix, Arizona, United States
Investigational Site Number 840024
🇺🇸Charleston, South Carolina, United States
Investigational Site Number 056002
🇧🇪Antwerpen, Belgium
Investigational Site Number 840010
🇺🇸Ann Arbor, Michigan, United States