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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01437787
First received: September 16, 2011
Last updated: April 7, 2014
Last verified: April 2014
  Purpose

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.

Condition Intervention Phase
Hematopoietic Neoplasm
Drug: SAR302503
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, 3-Arm Study of SAR302503 in Patients With Intermediate-2 or High-Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis With Splenomegaly

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • 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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Symptom Response Rate (SRR): Proportion of patients with ≥50% reduction from baseline to the end of Cycle 6 in the total symptom score. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    This assessment will be conducted through the modified MFSAF diary, which will be completed during the week prior to Day 1 of each treatment cycle up to Cycle 6, and during the week prior to the end of Cycle 6.

  • OS (overall survival) of either 400 mg/day or 500 mg/day of IMP as compared to placebo. [ Time Frame: approximately 5 years ] [ Designated as safety issue: No ]
  • PFS (progression free survival) of either 400 mg/day or 500 mg/day of IMP as compared to placebo. [ Time Frame: approximately 5 years ] [ Designated as safety issue: No ]
  • Proportion of patients who have ≥25% reduction in volume of spleen size at end of Cycle 6, and confirmed 4 weeks thereafter. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Duration of spleen response, measured by MRI (or CT scan in patients with contraindications for MRI. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Clinical and laboratory events graded by the NCI CTCAE v4.03. [ Time Frame: approximately 5 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 225
Study Start Date: December 2011
Estimated Study Completion Date: May 2014
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo comparator
once daily X 28 days, orally, empty stomach, approximately same time each day
Drug: Placebo

Pharmaceutical form:capsule

Route of administration: oral

Experimental: SAR302503 400 mg
once daily X 28 days, orally, empty stomach, approximately same time each day
Drug: SAR302503

Pharmaceutical form:capsule

Route of administration: oral

Experimental: SAR302503 500 mg
once daily X 28 days, orally, empty stomach, approximately same time each day
Drug: SAR302503

Pharmaceutical form:capsule

Route of administration: oral


Detailed Description:

The expected duration of a patient's 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 End Of Treatment (EOT) visit, which should be performed at least 30 days following the last administration of IMP or placebo.

Patients who continue to benefit clinically will be allowed to remain on IMP or placebo beyond the 6-month treatment period until the occurrence of disease progression or unacceptable toxicity.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • 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

Exclusion criteria:

  • 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.

  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 ClinicalTrials.gov identifier: NCT01437787

  Hide Study Locations
Locations
United States, Arizona
Investigational Site Number 840014
Scottsdale, Arizona, United States, 85259-5499
United States, California
Investigational Site Number 840006
Los Angeles, California, United States, 90033
Investigational Site Number 840001
San Francisco, California, United States, 94143
Investigational Site Number 840012
San Francisco, California, United States, 94143
United States, Louisiana
Investigational Site Number 840013
Baton Rouge, Louisiana, United States, 70808
United States, Minnesota
Investigational Site Number 840008
Rochester, Minnesota, United States, 55905
United States, New Jersey
Investigational Site Number 840009
Newark, New Jersey, United States, 07112
United States, Ohio
Investigational Site Number 840002
Canton, Ohio, United States, 44718
United States, Texas
Investigational Site Number 840004
Houston, Texas, United States, 77030
Australia
Investigational Site Number 036001
Box Hill, Australia, 3128
Investigational Site Number 036005
Herston, Australia, 4029
Investigational Site Number 036003
Randwick, Australia, 2031
Investigational Site Number 036004
Tweed Heads, Australia, 2485
Investigational Site Number 036002
Wodonga, Australia, 3690
Austria
Investigational Site Number 040001
Wien, Austria, 1090
Belgium
Investigational Site Number 056003
Antwerpen, Belgium, 2060
Investigational Site Number 056001
Leuven, Belgium, 3000
Brazil
Investigational Site Number 076002
Jau, Brazil, 17210-120
Investigational Site Number 076004
Porto Alegre, Brazil, 90110-270
Investigational Site Number 076001
Rio De Janeiro, Brazil, 20230-130
Canada
Investigational Site Number 124001
Montreal, Canada, H1T 2M4
Investigational Site Number 124003
Montreal, Canada, H2W 1S6
Investigational Site Number 124002
Saint John, Canada, E2L 4L2
France
Investigational Site Number 250006
Marseille, France, 13273
Investigational Site Number 250005
Nantes Cedex 01, France, 44093
Investigational Site Number 250004
Nimes, France, 30029
Investigational Site Number 250002
Pierre Benite Cedex, France, 69495
Investigational Site Number 250007
Poitiers, France, 86000
Investigational Site Number 250003
Toulouse, France, 31000
Investigational Site Number 250001
Villejuif Cedex, France, 94805
Germany
Investigational Site Number 276006
Aachen, Germany, 52074
Investigational Site Number 276007
Bonn, Germany, 53127
Investigational Site Number 276008
Dresden, Germany, 01307
Investigational Site Number 276001
Mannheim, Germany, 68167
Hungary
Investigational Site Number 348002
Budapest, Hungary, 1097
Investigational Site Number 348001
Debrecen, Hungary, 4032
Investigational Site Number 348007
Györ, Hungary, 9023
Investigational Site Number 348006
Kecskemét, Hungary, 6000
Investigational Site Number 348003
Miskolc, Hungary, 3529
Ireland
Investigational Site Number 372002
Dublin, Ireland, Dublin 8
Investigational Site Number 372001
Galway, Ireland
Israel
Investigational Site Number 376003
Haifa, Israel, 31048
Investigational Site Number 376002
Tel Hashomer, Israel, 52621
Italy
Investigational Site Number 380002
Bergamo, Italy, 24127
Investigational Site Number 380007
Bologna, Italy, 40138
Investigational Site Number 380004
Firenze, Italy, 50134
Investigational Site Number 380001
Pavia, Italy, 27100
Investigational Site Number 380006
Pavia, Italy, 27100
Investigational Site Number 380003
Varese, Italy, 21100
Korea, Republic of
Investigational Site Number 410002
Seongnam, Korea, Republic of, 463-707
Investigational Site Number 410006
Seoul, Korea, Republic of, 138-878
Investigational Site Number 410007
Seoul, Korea, Republic of
Investigational Site Number 410004
Seoul, Korea, Republic of, 110-744
Investigational Site Number 410005
Seoul, Korea, Republic of
Investigational Site Number 410003
Seoul, Korea, Republic of, 120-752
Investigational Site Number 410001
Seoul, Korea, Republic of, 135-710
Lithuania
Investigational Site Number 440001
Kaunas, Lithuania, LT-50009
Investigational Site Number 440002
Klaipeda, Lithuania, LT-92288
Mexico
Investigational Site Number 484001
Queretaro, Mexico, 76000
Poland
Investigational Site Number 616005
Brzozow, Poland, 36-200
Investigational Site Number 616002
Gdansk, Poland, 80-952
Investigational Site Number 616006
Lodz, Poland, 93-510
Investigational Site Number 616010
Warszawa, Poland, 02-106
Investigational Site Number 616003
Wroclaw, Poland, 50-367
Portugal
Investigational Site Number 620005
Coimbra, Portugal, 3000-075
Investigational Site Number 620001
Lisboa, Portugal, 1649-035
Investigational Site Number 620004
Lisboa, Portugal, 1169-050
Investigational Site Number 620003
Porto, Portugal, 4200-072
Romania
Investigational Site Number 642003
Brasov, Romania
Investigational Site Number 642004
Bucharest, Romania, 022328
Investigational Site Number 642006
Bucuresti, Romania
Investigational Site Number 642002
Bucuresti, Romania, 030171
Investigational Site Number 642001
Timisoara, Romania, 300329
Russian Federation
Investigational Site Number 643009
Moscow, Russian Federation, 125167
Investigational Site Number 643001
Moscow, Russian Federation, 125284
Investigational Site Number 643010
Nizhny Novgorod, Russian Federation, 603126
Investigational Site Number 643008
Petrozavodsk, Russian Federation, 185019
Investigational Site Number 643004
St-Petersburg, Russian Federation, 197341
Investigational Site Number 643005
St.-Petersburg, Russian Federation, 191024
Investigational Site Number 643007
Volgograd, Russian Federation, 400138
Singapore
Investigational Site Number 702002
Singapore, Singapore, 119228
Investigational Site Number 702001
Singapore, Singapore, 169608
South Africa
Investigational Site Number 710003
Johannesburg, South Africa, 2013
Investigational Site Number 710002
Parktown, South Africa, 2193
Spain
Investigational Site Number 724001
Barcelona, Spain, 08036
Investigational Site Number 724002
Madrid, Spain, 28046
Sweden
Investigational Site Number 752001
Stockholm, Sweden, 14186
Investigational Site Number 752002
Uddevalla, Sweden, 451 80
Taiwan
Investigational Site Number 158002
Changhua, Taiwan, 500
Investigational Site Number 158003
Kaohsiung, Taiwan, 833
Investigational Site Number 158001
Taipei, Taiwan, 112
United Kingdom
Investigational Site Number 826006
Belfast, United Kingdom, BT9 7AB
Investigational Site Number 826003
Birmingham, United Kingdom, B9 5SS
Investigational Site Number 826002
Glasgow, United Kingdom, G12 0YN
Investigational Site Number 826004
Leeds, United Kingdom, LS9 7TF
Investigational Site Number 826001
London, United Kingdom, SE1 9RT
Investigational Site Number 826005
London, United Kingdom, W12 0HS
Investigational Site Number 826007
Manchester, United Kingdom, M20 4BX
Investigational Site Number 826008
Newcastle Upon Tyne, United Kingdom, NE7 7DN
Investigational Site Number 826009
Oxford, United Kingdom, OX3 7LJ
Investigational Site Number 826010
Southampton, United Kingdom, SO16 6YD
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01437787     History of Changes
Other Study ID Numbers: EFC12153, 2011-001897-25, U1111-1121-7170
Study First Received: September 16, 2011
Last Updated: April 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Primary Myelofibrosis
Neoplasms
Thrombocythemia, Essential
Hematologic Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Blood Coagulation Disorders
Thrombocytosis
Blood Platelet Disorders
Hemorrhagic Disorders
Neoplasms by Site

ClinicalTrials.gov processed this record on July 26, 2014