Phase II, Open Label, Single Arm Study of SAR302503 In Myelofibrosis Patients Previously Treated With Ruxolitinib
Information source: Sanofi
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hematopoietic Neoplasm
Intervention: SAR302503 (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: Sanofi Official(s) and/or principal investigator(s): Clinical Sciences & Operations, Study Director, Affiliation: Sanofi
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
Clinical Details
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 design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: 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: 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 MFSAFDuration 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
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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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.
Locations and Contacts
Investigational Site Number 040002, Salzburg 5020, Austria
Investigational Site Number 040001, Wien 1090, Austria
Investigational Site Number 056002, Antwerpen 2060, Belgium
Investigational Site Number 056003, Leuven 3000, Belgium
Investigational Site Number 124001, Toronto M5G 2M9, Canada
Investigational Site Number 250001, Marseille 13273, France
Investigational Site Number 250003, Nimes Cedex 9 30029, France
Investigational Site Number 250002, Paris Cedex 10 75475, France
Investigational Site Number 250006, Paris Cedex 12 75571, France
Investigational Site Number 250004, Toulouse 31000, France
Investigational Site Number 276003, Frankfurt Am Main 60590, Germany
Investigational Site Number 276007, Leipzig 04103, Germany
Investigational Site Number 276006, Magdeburg 39120, Germany
Investigational Site Number 276001, Mannheim 68167, Germany
Investigational Site Number 276005, Ulm 89081, Germany
Investigational Site Number 380004, Firenze 50134, Italy
Investigational Site Number 380001, Milano 20122, Italy
Investigational Site Number 380002, Roma 00161, Italy
Investigational Site Number 380003, Varese 21100, Italy
Investigational Site Number 528002, Amsterdam 1081 HV, Netherlands
Investigational Site Number 528003, Maastricht 6229 HX, Netherlands
Investigational Site Number 528001, Nijmegen 6525 GA, Netherlands
Investigational Site Number 724001, Barcelona 08036, Spain
Investigational Site Number 724003, Majadahonda 28222, Spain
Investigational Site Number 724002, Salamanca 37007, Spain
Investigational Site Number 826001, London SE1 9RT, United Kingdom
Investigational Site Number 840007, Phoenix, Arizona 85054, United States
Investigational Site Number 840003, San Francisco, California 94143, United States
Investigational Site Number 840004, San Francisco, California 94143, United States
Investigational Site Number 840005, Atlanta, Georgia 30322, United States
Investigational Site Number 840014, Chicago, Illinois 60637, United States
Investigational Site Number 840001, Kansas City, Kansas 66160-7321, United States
Investigational Site Number 840013, Baltimore, Maryland 21229, United States
Investigational Site Number 840017, Baltimore, Maryland 21201, United States
Investigational Site Number 840010, Ann Arbor, Michigan 48109-0759, United States
Investigational Site Number 840009, New York, New York 10021, United States
Investigational Site Number 840018, New York, New York 10032, United States
Investigational Site Number 840022, Cleveland, Ohio 44195, United States
Investigational Site Number 840019, Middletown, Ohio 45042, United States
Investigational Site Number 840024, Charleston, South Carolina 29406, United States
Investigational Site Number 840002, Houston, Texas 77030, United States
Investigational Site Number 840015, Salt Lake City, Utah 84112-5550, United States
Additional Information
Starting date: April 2012
Last updated: June 10, 2014
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