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

NCT ID: NCT01523171

Last Updated: 2025-03-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 97 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-30
• Study Completion Date: 2014-04-30

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.

Conditions

Hematopoietic Neoplasm

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

SAR302503

Intervention Type: DRUG

Pharmaceutical form:capsule

Route of administration: oral

Interventions

SAR302503

Pharmaceutical form:capsule

Route of administration: oral

Intervention Type: DRUG

Eligibility 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 (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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 840007

Phoenix, Arizona, United States

Investigational Site Number 840003

San Francisco, California, United States

Investigational Site Number 840004

San Francisco, California, United States

Investigational Site Number 840005

Atlanta, Georgia, 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 840013

Baltimore, Maryland, United States

Investigational Site Number 840010

Ann Arbor, Michigan, United States

Investigational Site Number 840009

New York, New York, United States

Investigational Site Number 840018

New York, New York, United States

Investigational Site Number 840022

Cleveland, Ohio, United States

Investigational Site Number 840019

Middletown, Ohio, United States

Investigational Site Number 840024

Charleston, South Carolina, United States

Investigational Site Number 840002

Houston, Texas, United States

Investigational Site Number 840015

Salt Lake City, Utah, United States

Investigational Site Number 040002

Salzburg, , Austria

Investigational Site Number 040001

Vienna, , Austria

Investigational Site Number 056002

Antwerp, , Belgium

Investigational Site Number 056003

Leuven, , Belgium

Investigational Site Number 124001

Toronto, , Canada

Investigational Site Number 250001

Marseille, , France

Investigational Site Number 250003

Nîmes, , France

Investigational Site Number 250002

Paris, , France

Investigational Site Number 250006

Paris, , France

Investigational Site Number 250004

Toulouse, , France

Investigational Site Number 276003

Frankfurt am Main, , Germany

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 380004

Florence, , Italy

Investigational Site Number 380001

Milan, , Italy

Investigational Site Number 380002

Roma, , Italy

Investigational Site Number 380003

Varese, , Italy

Investigational Site Number 528002

Amsterdam, , Netherlands

Investigational Site Number 528003

Maastricht, , Netherlands

Investigational Site Number 528001

Nijmegen, , Netherlands

Investigational Site Number 724001

Barcelona, , Spain

Investigational Site Number 724003

Majadahonda, , Spain

Investigational Site Number 724002

Salamanca, , Spain

Investigational Site Number 826001

London, , United Kingdom

Countries

United States; Austria; Belgium; Canada; France; Germany; Italy; Netherlands; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 28602585 (View on PubMed)

Other Identifiers

2011-005226-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1124-0967

Identifier Type: OTHER

Identifier Source: secondary_id

ARD12181

Identifier Type: -

Identifier Source: org_study_id