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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 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

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

Page last updated: August 23, 2015

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