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Phase II, Open Label, Single Arm Study of SAR302503 In Myelofibrosis Patients Previously Treated With Ruxolitinib (JAKARTA2)

This study has been completed.
Information provided by (Responsible Party):
Sanofi Identifier:
First received: January 27, 2012
Last updated: February 17, 2016
Last verified: February 2016

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

Condition Intervention Phase
Hematopoietic Neoplasm
Drug: SAR302503
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II, Multicenter, Open Label, Single Arm Study of SAR302503 in Subjects Previously Treated With Ruxolitinib and With a Current Diagnosis of Intermediate or High-Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis

Resource links provided by NLM:

Further study details as provided by Sanofi:

Primary Outcome Measures:
  • 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) [ Time Frame: 6 months ]

Secondary Outcome Measures:
  • 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 [ Time Frame: 6 months ]
  • Duration of spleen response, measured by MRI (or CT scan in subjects with contraindications for MRI) [ Time Frame: 6 months ]
  • Proportion of subjects with a ≥50% reduction in length of spleen by palpation from baseline at the end of Cycle 6 [ Time Frame: 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) [ Time Frame: 6 months ]
  • 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) [ Time Frame: 6 months ]
  • Safety, as assessed by clinical, laboratory, ECG, and vital sign events; graded by the NCI CTCAE v4.03 [ Time Frame: approximately 5 years ]
  • Plasma concentrations of SAR302503 [ Time Frame: 4 months ]
  • The effect of SAR302503 on the JAK2V617F allele burden [ Time Frame: 2 years ]

Enrollment: 97
Study Start Date: April 2012
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SAR302503 400 mg
once daily in consecutive 28-day cycles, flexible dosing regimen (the starting dose is 400mg/day), orally, empty stomach, approximately same time each day
Drug: SAR302503

Pharmaceutical form:capsule

Route of administration: oral

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.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01523171

  Hide Study Locations
United States, Arizona
Investigational Site Number 840007
Phoenix, Arizona, United States, 85054
United States, California
Investigational Site Number 840003
San Francisco, California, United States, 94143
Investigational Site Number 840004
San Francisco, California, United States, 94143
United States, Georgia
Investigational Site Number 840005
Atlanta, Georgia, United States, 30322
United States, Illinois
Investigational Site Number 840014
Chicago, Illinois, United States, 60637
United States, Kansas
Investigational Site Number 840001
Kansas City, Kansas, United States, 66160-7321
United States, Maryland
Investigational Site Number 840017
Baltimore, Maryland, United States, 21201
Investigational Site Number 840013
Baltimore, Maryland, United States, 21229
United States, Michigan
Investigational Site Number 840010
Ann Arbor, Michigan, United States, 48109-0759
United States, New York
Investigational Site Number 840009
New York, New York, United States, 10021
Investigational Site Number 840018
New York, New York, United States, 10032
United States, Ohio
Investigational Site Number 840022
Cleveland, Ohio, United States, 44195
Investigational Site Number 840019
Middletown, Ohio, United States, 45042
United States, South Carolina
Investigational Site Number 840024
Charleston, South Carolina, United States, 29406
United States, Texas
Investigational Site Number 840002
Houston, Texas, United States, 77030
United States, Utah
Investigational Site Number 840015
Salt Lake City, Utah, United States, 84112-5550
Investigational Site Number 040002
Salzburg, Austria, 5020
Investigational Site Number 040001
Wien, Austria, 1090
Investigational Site Number 056002
Antwerpen, Belgium, 2060
Investigational Site Number 056003
Leuven, Belgium, 3000
Investigational Site Number 124001
Toronto, Canada, M5G 2M9
Investigational Site Number 250001
Marseille, France, 13273
Investigational Site Number 250003
Nimes Cedex 9, France, 30029
Investigational Site Number 250002
Paris Cedex 10, France, 75475
Investigational Site Number 250006
Paris Cedex 12, France, 75571
Investigational Site Number 250004
Toulouse, France, 31000
Investigational Site Number 276003
Frankfurt Am Main, Germany, 60590
Investigational Site Number 276007
Leipzig, Germany, 04103
Investigational Site Number 276006
Magdeburg, Germany, 39120
Investigational Site Number 276001
Mannheim, Germany, 68167
Investigational Site Number 276005
Ulm, Germany, 89081
Investigational Site Number 380004
Firenze, Italy, 50134
Investigational Site Number 380001
Milano, Italy, 20122
Investigational Site Number 380002
Roma, Italy, 00161
Investigational Site Number 380003
Varese, Italy, 21100
Investigational Site Number 528002
Amsterdam, Netherlands, 1081 HV
Investigational Site Number 528003
Maastricht, Netherlands, 6229 HX
Investigational Site Number 528001
Nijmegen, Netherlands, 6525 GA
Investigational Site Number 724001
Barcelona, Spain, 08036
Investigational Site Number 724003
Majadahonda, Spain, 28222
Investigational Site Number 724002
Salamanca, Spain, 37007
United Kingdom
Investigational Site Number 826001
London, United Kingdom, SE1 9RT
Sponsors and Collaborators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

Responsible Party: Sanofi Identifier: NCT01523171     History of Changes
Other Study ID Numbers: ARD12181
2011-005226-21 ( EudraCT Number )
U1111-1124-0967 ( Other Identifier: UTN )
Study First Received: January 27, 2012
Last Updated: February 17, 2016

Additional relevant MeSH terms:
Primary Myelofibrosis
Hematologic Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Neoplasms by Site
Neoplasms processed this record on April 26, 2017