Phase III Study of SAR302503 in Intermediate-2 and High Risk Patients With Myelofibrosis

NCT01437787 | Completed Phase 3

• 3 other identifiers: EFC121532011-001897-25U1111-1121-7170
• Study Type: interventional
• Target: 289
• Locations: 24 countries
• Sites: 100

Brief Summary

Primary Objective:

• To evaluate the efficacy of daily oral doses of 400 mg or 500 mg of SAR302503 (Investigational Medicinal Product, IMP) compared to placebo in the reduction of spleen volume as determined by magnetic resonance imaging (MRI) (or computed tomography scan in patients with contraindications for MRI). Secondary Objectives:
• To evaluate the effect on Myelofibrosis (MF)-associated symptoms (key MF symptoms) as measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF) diary.
• To evaluate the Overall Survival of patients treated with either 400 mg/day or 500 mg/day of IMP as compared to placebo.
• To evaluate the Progression Free Survival of patients treated with either 400 mg/day or 500 mg/day of IMP as compared to placebo.
• To evaluate the durability of splenic response.
• To evaluate the safety of IMP.

Conditions

Hematopoietic Neoplasm

Outcome Measures

Primary Outcomes (1)

• Response Rate (RR), defined as the proportion of patients who have a ≥35% reduction in volume of spleen size at the end of Cycle 6, and confirmed 4 weeks thereafter

  6 months

Secondary Outcomes (6)

• Symptom Response Rate (SRR): Proportion of patients with ≥50% reduction from baseline to the end of Cycle 6 in the total symptom score.

  6 months

• OS (overall survival) of either 400 mg/day or 500 mg/day of IMP as compared to placebo.

  approximately 5 years

• PFS (progression free survival) of either 400 mg/day or 500 mg/day of IMP as compared to placebo.

  approximately 5 years

• Proportion of patients who have ≥25% reduction in volume of spleen size at end of Cycle 6, and confirmed 4 weeks thereafter.

  6 months

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

  2 years

Study Arms (3)

Placebo comparator

PLACEBO COMPARATOR

once daily X 28 days, orally, empty stomach, approximately same time each day

Drug: Placebo

SAR302503 400 mg

EXPERIMENTAL

once daily X 28 days, orally, empty stomach, approximately same time each day

Drug: SAR302503

SAR302503 500 mg

EXPERIMENTAL

once daily X 28 days, orally, empty stomach, approximately same time each day

Drug: SAR302503

Interventions

SAR302503 DRUG

Pharmaceutical form:capsule Route of administration: oral

SAR302503 400 mg; SAR302503 500 mg

Placebo DRUG

Pharmaceutical form:capsule Route of administration: oral

Placebo comparator

Eligibility Criteria

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

You may qualify if:

• Diagnosis of Primary Myelofibrosis (MF) or Post-Polycythemia Vera MF or Post-Essential Thrombocythemia MF, according to the 2008 World Health Organization and International Working Group of Myelofibrosis Research and Treatment (IWG-MRT) criteria.
• MF classified as high-risk or intermediate-risk level 2, as defined by modified IWG-MRT criteria (IPSS) (according to Cervantes F. et. al.; at screening).
• Enlarged spleen, palpable at least 5 cm below costal margin.
• At least 18 years of age.
• Eastern Cooperative Oncology Group performance status of 0, 1, or 2 at study entry.
• The following laboratory values within 14 days prior to the initiation of IMP or placebo:
• 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

You may not qualify if:

• Splenectomy.
• Any chemotherapy (eg, hydroxyurea), 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 IMP or placebo; darbepoetin use within 28 days prior to initiation of IMP or placebo. Patients who have had exposure to hydroxyurea (eg, hydrea) in the past may be enrolled into the study as long as it has not been administered within 14 days prior to initiation of IMP or placebo.
• Major surgery within 28 days or radiation within 6 months prior to initiation of IMP or placebo.
• Prior treatment with a Janus Kinase 2 (JAK2) inhibitor.
• Known active (acute or chronic) Hepatitis A, B, or C; and hepatitis B and C carriers
• AST or ALT ≥2.5 x ULN
• Total Bilirubin:
• Exclude if ≥3.0 x ULN
• Patients with total bilirubin between 1.5-3.0 x ULN must be excluded if the direct bilirubin fraction is ≥25% of the total
• Prior history of chronic liver disease (eg, chronic alcoholic liver disease, autoimmune hepatitis, sclerosing cholangitis, primary biliary cirrhosis, hemachromatosis, non-alcoholic steatohepatitis \[NASH\])
• The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (101)

Investigational Site Number 840014

Scottsdale, Arizona, 85259-5499, United States

Location

Investigational Site Number 840001

La Jolla, California, 92093, United States

Location

Investigational Site Number 840012

La Jolla, California, 92093, United States

Location

Investigational Site Number 840006

Los Angeles, California, 90033, United States

Location

Investigational Site Number 840013

Baton Rouge, Louisiana, 70808, United States

Location

Investigational Site Number 840008

Rochester, Minnesota, 55905, United States

Location

Investigational Site Number 840009

Newark, New Jersey, 07112, United States

Location

Investigational Site Number 840002

Canton, Ohio, 44718, United States

Location

Investigational Site Number 840004

Houston, Texas, 77030, United States

Location

Investigational Site Number 036001

Box Hill, 3128, Australia

Location

Investigational Site Number 036005

Herston, 4029, Australia

Location

Investigational Site Number 036003

Randwick, 2031, Australia

Location

Investigational Site Number 036004

Tweed Heads, 2485, Australia

Location

Investigational Site Number 036002

Wodonga, 3690, Australia

Location

Investigational Site Number 040001

Vienna, 1090, Austria

Location

Investigational Site Number 056003

Antwerp, 2060, Belgium

Location

Investigational Site Number 056001

Leuven, 3000, Belgium

Location

Investigational Site Number 076002

Jaú, 17210-120, Brazil

Location

Investigational Site Number 076004

Porto Alegre, 90110-270, Brazil

Location

Investigational Site Number 076001

Rio de Janeiro, 20230-130, Brazil

Location

Investigational Site Number 124001

Montreal, H1T 2M4, Canada

Location

Investigational Site Number 124003

Montreal, H2W 1S6, Canada

Location

Investigational Site Number 124002

Saint John, E2L 4L2, Canada

Location

Investigational Site Number 250006

Marseille, 13273, France

Location

Investigational Site Number 250005

Nantes, 44093, France

Location

Investigational Site Number 250004

Nîmes, 30029, France

Location

Investigational Site Number 250002

Pierre-Bénite, 69495, France

Location

Investigational Site Number 250007

Poitiers, 86000, France

Location

Investigational Site Number 250003

Toulouse, 31000, France

Location

Investigational Site Number 250001

Villejuif, 94805, France

Location

Investigational Site Number 276006

Aachen, 52074, Germany

Location

Investigational Site Number 276007

Bonn, 53127, Germany

Location

Investigational Site Number 276008

Dresden, 01307, Germany

Location

Investigational Site Number 276001

Mannheim, 68167, Germany

Location

Investigational Site Number 348002

Budapest, 1097, Hungary

Location

Investigational Site Number 348001

Debrecen, 4032, Hungary

Location

Investigational Site Number 348007

Győr, 9023, Hungary

Location

Investigational Site Number 348006

Kecskemét, 6000, Hungary

Location

Investigational Site Number 348003

Miskolc, 3529, Hungary

Location

Investigational Site Number 372002

Dublin, DUBLIN 8, Ireland

Location

Investigational Site Number 372001

Galway, Ireland

Location

Investigational Site Number 376003

Haifa, 31048, Israel

Location

Investigational Site Number 376002

Tel Litwinsky, 52621, Israel

Location

Investigational Site Number 380002

Bergamo, 24127, Italy

Location

Investigational Site Number 380007

Bologna, 40138, Italy

Location

Investigational Site Number 380004

Florence, 50134, Italy

Location

Investigational Site Number 380001

Pavia, 27100, Italy

Location

Investigational Site Number 380006

Pavia, 27100, Italy

Location

Investigational Site Number 380003

Varese, 21100, Italy

Location

Investigational Site Number 440001

Kaunas, LT-50009, Lithuania

Location

Investigational Site Number 440002

Klaipėda, LT-92288, Lithuania

Location

Investigational Site Number 484001

Querétaro, 76000, Mexico

Location

Investigational Site Number 616005

Brzozów, 36-200, Poland

Location

Investigational Site Number 616002

Gdansk, 80-952, Poland

Location

Investigational Site Number 616006

Lodz, 93-510, Poland

Location

Investigational Site Number 616010

Warsaw, 02-106, Poland

Location

Investigational Site Number 616003

Wroclaw, 50-367, Poland

Location

Investigational Site Number 620005

Coimbra, 3000-075, Portugal

Location

Investigational Site Number 620004

Lisbon, 1169-050, Portugal

Location

Investigational Site Number 620001

Lisbon, 1649-035, Portugal

Location

Investigational Site Number 620003

Porto, 4200-072, Portugal

Location

Investigational Site Number 642003

Brasov, Romania

Location

Investigational Site Number 642004

Bucharest, 022328, Romania

Location

Investigational Site Number 642002

Bucharest, 030171, Romania

Location

Investigational Site Number 642006

Bucharest, Romania

Location

Investigational Site Number 642001

Timișoara, Romania

Location

Investigational Site Number 643009

Moscow, 125167, Russia

Location

Investigational Site Number 643001

Moscow, 125284, Russia

Location

Investigational Site Number 643010

Nizhny Novgorod, 603126, Russia

Location

Investigational Site Number 643008

Petrozavodsk, 185019, Russia

Location

Investigational Site Number 643005

Saint Petersburg, 191024, Russia

Location

Investigational Site Number 643004

Saint Petersburg, 197341, Russia

Location

Investigational Site Number 643007

Volgograd, 400138, Russia

Location

Investigational Site Number 702002

Singapore, 119228, Singapore

Location

Investigational Site Number 702001

Singapore, 169608, Singapore

Location

Investigational Site Number 710003

Johannesburg, 2013, South Africa

Location

Investigational Site Number 710002

Parktown, 2193, South Africa

Location

Investigational Site Number 410002

Bundang-Gu, 463-707, South Korea

Location

Investigational Site Number 410004

Seoul, 110-744, South Korea

Location

Investigational Site Number 410003

Seoul, 120-752, South Korea

Location

Investigational Site Number 410001

Seoul, 135-710, South Korea

Location

Investigational Site Number 410005

Seoul, 137-701, South Korea

Location

Investigational Site Number 410006

Seoul, 138-878, South Korea

Location

Investigational Site Number 410007

Seoul, South Korea

Location

Investigational Site Number 724001

Barcelona, 08036, Spain

Location

Investigational Site Number 724002

Madrid, 28046, Spain

Location

Investigational Site Number 752001

Stockholm, 14186, Sweden

Location

Investigational Site Number 752002

Uddevalla, 451 80, Sweden

Location

Investigational Site Number 158002

Changhua, 500, Taiwan

Location

Investigational Site Number 158003

Kaohsiung City, 833, Taiwan

Location

Investigational Site Number 158001

Taipei, 112, Taiwan

Location

Investigational Site Number 826006

Belfast, BT9 7AB, United Kingdom

Location

Investigational Site Number 826003

Birmingham, B9 5SS, United Kingdom

Location

Investigational Site Number 826002

Glasgow, G12 0YN, United Kingdom

Location

Investigational Site Number 826004

Leeds, LS9 7TF, United Kingdom

Location

Investigational Site Number 826001

London, SE1 9RT, United Kingdom

Location

Investigational Site Number 826005

London, W12 0HS, United Kingdom

Location

Investigational Site Number 826007

Manchester, M20 4BX, United Kingdom

Location

Investigational Site Number 826008

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Investigational Site Number 826009

Oxford, OX3 7LJ, United Kingdom

Location

Investigational Site Number 826010

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (1)

• Pardanani A, Harrison C, Cortes JE, Cervantes F, Mesa RA, Milligan D, Masszi T, Mishchenko E, Jourdan E, Vannucchi AM, Drummond MW, Jurgutis M, Kuliczkowski K, Gheorghita E, Passamonti F, Neumann F, Patki A, Gao G, Tefferi A. Safety and Efficacy of Fedratinib in Patients With Primary or Secondary Myelofibrosis: A Randomized Clinical Trial. JAMA Oncol. 2015 Aug;1(5):643-51. doi: 10.1001/jamaoncol.2015.1590.

  PMID: 26181658 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 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2011
• First Posted: September 21, 2011
• Study Start: December 1, 2011
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: March 5, 2025

Record last verified: 2015-12

Locations

PT (4); SE (2); AU (5); CA (3); GB (10); HU (5); LI (2); BE (2); DE (4); TW (3); IE (2); ES (2); ME (1); IT (6); PL (5); BR (3); FR (7); IL (2); RO (5); US (9); SG (2); RU (7); ZA (2); KR (7)