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

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ClinicalTrials.gov Identifier: NCT01523171
Recruitment Status : Completed
First Posted : February 1, 2012
Last Update Posted : March 17, 2016
Sponsor:
Information provided by (Responsible Party):
Sanofi

Tracking Information
First Submitted Date  ICMJE January 27, 2012
First Posted Date  ICMJE February 1, 2012
Last Update Posted Date March 17, 2016
Study Start Date  ICMJE April 2012
Actual Primary Completion Date April 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 31, 2012)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 11, 2013)
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 31, 2012)
  • 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 by Cycle 6 (RR6), defined as the proportion of subjects who have a ≥35% reduction from baseline in volume of spleen at any time up to Cycle 6 as measured by MRI (or CT scan in subjects with contraindications for MRI) [ Time Frame: 6 months ]
  • The effect of SAR302503 on the JAK2V617F allele burden [ Time Frame: 2 years ]
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase II, Open Label, Single Arm Study of SAR302503 In Myelofibrosis Patients Previously Treated With Ruxolitinib
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hematopoietic Neoplasm
Intervention  ICMJE Drug: SAR302503

Pharmaceutical form:capsule

Route of administration: oral

Study Arms  ICMJE 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
Intervention: Drug: SAR302503
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 10, 2014)
97
Original Estimated Enrollment  ICMJE
 (submitted: January 31, 2012)
41
Actual Study Completion Date  ICMJE April 2014
Actual Primary Completion Date April 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Belgium,   Canada,   France,   Germany,   Italy,   Netherlands,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01523171
Other Study ID Numbers  ICMJE ARD12181
2011-005226-21 ( EudraCT Number )
U1111-1124-0967 ( Other Identifier: UTN )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sanofi
Study Sponsor  ICMJE Sanofi
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date February 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP