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

NCT01523171 | Completed Phase 2

• 3 other identifiers: ARD121812011-005226-21U1111-1124-0967
• Study Type: interventional
• Target: 97
• Locations: 10 countries
• Sites: 42

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

Conditions

Hematopoietic Neoplasm

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• 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

• Duration of spleen response, measured by MRI (or CT scan in subjects with contraindications for MRI)

  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

• 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

Study Arms (1)

SAR302503 400 mg

EXPERIMENTAL

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

Interventions

SAR302503 DRUG

Pharmaceutical form:capsule Route of administration: oral

SAR302503 400 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (42)

Investigational Site Number 840007

Phoenix, Arizona, 85054, United States

Location

Investigational Site Number 840003

San Francisco, California, 94143, United States

Location

Investigational Site Number 840004

San Francisco, California, 94143, United States

Location

Investigational Site Number 840005

Atlanta, Georgia, 30322, United States

Location

Investigational Site Number 840014

Chicago, Illinois, 60637, United States

Location

Investigational Site Number 840001

Kansas City, Kansas, 66160-7321, United States

Location

Investigational Site Number 840017

Baltimore, Maryland, 21201, United States

Location

Investigational Site Number 840013

Baltimore, Maryland, 21229, United States

Location

Investigational Site Number 840010

Ann Arbor, Michigan, 48109-0759, United States

Location

Investigational Site Number 840009

New York, New York, 10021, United States

Location

Investigational Site Number 840018

New York, New York, 10032, United States

Location

Investigational Site Number 840022

Cleveland, Ohio, 44195, United States

Location

Investigational Site Number 840019

Middletown, Ohio, 45042, United States

Location

Investigational Site Number 840024

Charleston, South Carolina, 29406, United States

Location

Investigational Site Number 840002

Houston, Texas, 77030, United States

Location

Investigational Site Number 840015

Salt Lake City, Utah, 84112-5550, United States

Location

Investigational Site Number 040002

Salzburg, 5020, Austria

Location

Investigational Site Number 040001

Vienna, 1090, Austria

Location

Investigational Site Number 056002

Antwerp, 2060, Belgium

Location

Investigational Site Number 056003

Leuven, 3000, Belgium

Location

Investigational Site Number 124001

Toronto, M5G 2M9, Canada

Location

Investigational Site Number 250001

Marseille, 13273, France

Location

Investigational Site Number 250003

Nîmes, 30029, France

Location

Investigational Site Number 250002

Paris, 75475, France

Location

Investigational Site Number 250006

Paris, 75571, France

Location

Investigational Site Number 250004

Toulouse, 31000, France

Location

Investigational Site Number 276003

Frankfurt am Main, 60590, Germany

Location

Investigational Site Number 276007

Leipzig, 04103, Germany

Location

Investigational Site Number 276006

Magdeburg, 39120, Germany

Location

Investigational Site Number 276001

Mannheim, 68167, Germany

Location

Investigational Site Number 276005

Ulm, 89081, Germany

Location

Investigational Site Number 380004

Florence, 50134, Italy

Location

Investigational Site Number 380001

Milan, 20122, Italy

Location

Investigational Site Number 380002

Roma, 00161, Italy

Location

Investigational Site Number 380003

Varese, 21100, Italy

Location

Investigational Site Number 528002

Amsterdam, 1081 HV, Netherlands

Location

Investigational Site Number 528003

Maastricht, 6229 HX, Netherlands

Location

Investigational Site Number 528001

Nijmegen, 6525 GA, Netherlands

Location

Investigational Site Number 724001

Barcelona, 08036, Spain

Location

Investigational Site Number 724003

Majadahonda, 28222, Spain

Location

Investigational Site Number 724002

Salamanca, 37007, Spain

Location

Investigational Site Number 826001

London, SE1 9RT, United Kingdom

Location

Related Publications (1)

• Harrison CN, Schaap N, Vannucchi AM, Kiladjian JJ, Tiu RV, Zachee P, Jourdan E, Winton E, Silver RT, Schouten HC, Passamonti F, Zweegman S, Talpaz M, Lager J, Shun Z, Mesa RA. Janus kinase-2 inhibitor fedratinib in patients with myelofibrosis previously treated with ruxolitinib (JAKARTA-2): a single-arm, open-label, non-randomised, phase 2, multicentre study. Lancet Haematol. 2017 Jul;4(7):e317-e324. doi: 10.1016/S2352-3026(17)30088-1. Epub 2017 Jun 8.

  PMID: 28602585 DERIVED

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

fedratinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2012
• First Posted: February 1, 2012
• Study Start: April 1, 2012
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: March 5, 2025

Record last verified: 2016-02

Locations

NL (3); DE (5); ES (3); CA (1); US (16); GB (1); IT (4); AU (2); FR (5); BE (2)