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

This study is currently recruiting participants.
Verified May 2013 by Sanofi
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01523171
First received: January 27, 2012
Last updated: May 15, 2013
Last verified: May 2013
History of Changes
  Purpose

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

Condition Intervention Phase
Hematopoietic Neoplasm
 Drug: SAR302503
 Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

Drug Information available for: Ruxolitinib
U.S. FDA Resources

Further study details as provided by Sanofi:

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) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Duration of spleen response, measured by MRI (or CT scan in subjects with contraindications for MRI) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Safety, as assessed by clinical, laboratory, ECG, and vital sign events; graded by the NCI CTCAE v4.03 [ Time Frame: approximately 5 years ] [ Designated as safety issue: Yes ]
  • Plasma concentrations of SAR302503 [ Time Frame: 4 months ] [ Designated as safety issue: No ]
  • The effect of SAR302503 on the JAK2V617F allele burden [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 70
Study Start Date: April 2012
Estimated Study Completion Date: May 2019
Estimated Primary Completion Date: May 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
 Drug: SAR302503

Pharmaceutical form:capsule

Route of administration: oral

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.

  Eligibility

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

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01523171

Contacts
Contact: For site information, send an email with site number to Contact-Us@sanofi.com

  Show 42 Study Locations
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01523171     History of Changes
Other Study ID Numbers: ARD12181, 2011-005226-21, U1111-1124-0967
Study First Received: January 27, 2012
Last Updated: May 15, 2013
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 May 23, 2013