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

Primary Purpose

Hematopoietic Neoplasm

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
SAR302503
Sponsored by
Sanofi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hematopoietic Neoplasm

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Investigational Site Number 840007
  • Investigational Site Number 840003
  • Investigational Site Number 840004
  • Investigational Site Number 840005
  • Investigational Site Number 840014
  • Investigational Site Number 840001
  • Investigational Site Number 840017
  • Investigational Site Number 840013
  • Investigational Site Number 840010
  • Investigational Site Number 840009
  • Investigational Site Number 840018
  • Investigational Site Number 840022
  • Investigational Site Number 840019
  • Investigational Site Number 840024
  • Investigational Site Number 840002
  • Investigational Site Number 840015
  • Investigational Site Number 040002
  • Investigational Site Number 040001
  • Investigational Site Number 056002
  • Investigational Site Number 056003
  • Investigational Site Number 124001
  • Investigational Site Number 250001
  • Investigational Site Number 250003
  • Investigational Site Number 250002
  • Investigational Site Number 250006
  • Investigational Site Number 250004
  • Investigational Site Number 276003
  • Investigational Site Number 276007
  • Investigational Site Number 276006
  • Investigational Site Number 276001
  • Investigational Site Number 276005
  • Investigational Site Number 380004
  • Investigational Site Number 380001
  • Investigational Site Number 380002
  • Investigational Site Number 380003
  • Investigational Site Number 528002
  • Investigational Site Number 528003
  • Investigational Site Number 528001
  • Investigational Site Number 724001
  • Investigational Site Number 724003
  • Investigational Site Number 724002
  • Investigational Site Number 826001

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

SAR302503 400 mg

Arm Description

once daily in consecutive 28-day cycles, flexible dosing regimen (the starting dose is 400mg/day), orally, empty stomach, approximately same time each day

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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
Duration of spleen response, measured by MRI (or CT scan in subjects with contraindications for MRI)
Proportion of subjects with a ≥50% reduction in length of spleen by palpation from baseline at the end of Cycle 6
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)
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)
Safety, as assessed by clinical, laboratory, ECG, and vital sign events; graded by the NCI CTCAE v4.03
Plasma concentrations of SAR302503
The effect of SAR302503 on the JAK2V617F allele burden

Full Information

First Posted
January 27, 2012
Last Updated
February 17, 2016
Sponsor
Sanofi
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1. Study Identification

Unique Protocol Identification Number
NCT01523171
Brief Title
Phase II, Open Label, Single Arm Study of SAR302503 In Myelofibrosis Patients Previously Treated With Ruxolitinib
Acronym
JAKARTA2
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2016
Overall Recruitment Status
Completed
Study Start Date
April 2012 (undefined)
Primary Completion Date
April 2014 (Actual)
Study Completion Date
April 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematopoietic Neoplasm

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
97 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SAR302503 400 mg
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
SAR302503
Intervention Description
Pharmaceutical form:capsule Route of administration: oral
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
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
Title
Duration of spleen response, measured by MRI (or CT scan in subjects with contraindications for MRI)
Time Frame
6 months
Title
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
Title
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
Title
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
Title
Safety, as assessed by clinical, laboratory, ECG, and vital sign events; graded by the NCI CTCAE v4.03
Time Frame
approximately 5 years
Title
Plasma concentrations of SAR302503
Time Frame
4 months
Title
The effect of SAR302503 on the JAK2V617F allele burden
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number 840007
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Facility Name
Investigational Site Number 840003
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Investigational Site Number 840004
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Investigational Site Number 840005
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Investigational Site Number 840014
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Investigational Site Number 840001
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160-7321
Country
United States
Facility Name
Investigational Site Number 840017
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Investigational Site Number 840013
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21229
Country
United States
Facility Name
Investigational Site Number 840010
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-0759
Country
United States
Facility Name
Investigational Site Number 840009
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Investigational Site Number 840018
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Investigational Site Number 840022
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Investigational Site Number 840019
City
Middletown
State/Province
Ohio
ZIP/Postal Code
45042
Country
United States
Facility Name
Investigational Site Number 840024
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29406
Country
United States
Facility Name
Investigational Site Number 840002
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Investigational Site Number 840015
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112-5550
Country
United States
Facility Name
Investigational Site Number 040002
City
Salzburg
ZIP/Postal Code
5020
Country
Austria
Facility Name
Investigational Site Number 040001
City
Wien
ZIP/Postal Code
1090
Country
Austria
Facility Name
Investigational Site Number 056002
City
Antwerpen
ZIP/Postal Code
2060
Country
Belgium
Facility Name
Investigational Site Number 056003
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Investigational Site Number 124001
City
Toronto
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Investigational Site Number 250001
City
Marseille
ZIP/Postal Code
13273
Country
France
Facility Name
Investigational Site Number 250003
City
Nimes Cedex 9
ZIP/Postal Code
30029
Country
France
Facility Name
Investigational Site Number 250002
City
Paris Cedex 10
ZIP/Postal Code
75475
Country
France
Facility Name
Investigational Site Number 250006
City
Paris Cedex 12
ZIP/Postal Code
75571
Country
France
Facility Name
Investigational Site Number 250004
City
Toulouse
ZIP/Postal Code
31000
Country
France
Facility Name
Investigational Site Number 276003
City
Frankfurt Am Main
ZIP/Postal Code
60590
Country
Germany
Facility Name
Investigational Site Number 276007
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Investigational Site Number 276006
City
Magdeburg
ZIP/Postal Code
39120
Country
Germany
Facility Name
Investigational Site Number 276001
City
Mannheim
ZIP/Postal Code
68167
Country
Germany
Facility Name
Investigational Site Number 276005
City
Ulm
ZIP/Postal Code
89081
Country
Germany
Facility Name
Investigational Site Number 380004
City
Firenze
ZIP/Postal Code
50134
Country
Italy
Facility Name
Investigational Site Number 380001
City
Milano
ZIP/Postal Code
20122
Country
Italy
Facility Name
Investigational Site Number 380002
City
Roma
ZIP/Postal Code
00161
Country
Italy
Facility Name
Investigational Site Number 380003
City
Varese
ZIP/Postal Code
21100
Country
Italy
Facility Name
Investigational Site Number 528002
City
Amsterdam
ZIP/Postal Code
1081 HV
Country
Netherlands
Facility Name
Investigational Site Number 528003
City
Maastricht
ZIP/Postal Code
6229 HX
Country
Netherlands
Facility Name
Investigational Site Number 528001
City
Nijmegen
ZIP/Postal Code
6525 GA
Country
Netherlands
Facility Name
Investigational Site Number 724001
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Investigational Site Number 724003
City
Majadahonda
ZIP/Postal Code
28222
Country
Spain
Facility Name
Investigational Site Number 724002
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Facility Name
Investigational Site Number 826001
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
28602585
Citation
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.
Results Reference
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Phase II, Open Label, Single Arm Study of SAR302503 In Myelofibrosis Patients Previously Treated With Ruxolitinib

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