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

Phase 2

Completed

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

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

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

Locations (42): Investigational Site Number 840007
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Phoenix, Arizona, United States
Investigational Site Number 840003
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San Francisco, California, United States
Investigational Site Number 840004
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San Francisco, California, United States
Investigational Site Number 840005
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Atlanta, Georgia, United States
Investigational Site Number 840014
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Chicago, Illinois, United States
Investigational Site Number 840001
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Kansas City, Kansas, United States
Investigational Site Number 840017
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Baltimore, Maryland, United States
Investigational Site Number 840013
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Baltimore, Maryland, United States
Investigational Site Number 840010
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Ann Arbor, Michigan, United States
Investigational Site Number 840009
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New York, New York, United States
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Investigational Site Number 840007
🇺🇸Phoenix, Arizona, United States