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

Hematopoietic Neoplasm Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01523171
• Other study ID #: ARD12181
• Secondary ID: 2011-005226-21U1
• Status: Completed
• Phase: Phase 2
• First received: January 27, 2012
• Last updated: February 17, 2016
• Start date: April 2012
• Est. completion date: April 2014

Study information

• Verified date: February 2016
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 97
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Hematopoietic Neoplasm
• Primary Myelofibrosis

Intervention

Drug:
• SAR302503
Pharmaceutical form:capsule Route of administration: oral

Locations

Country	Name	City	State
Austria	Investigational Site Number 040002	Salzburg
Austria	Investigational Site Number 040001	Wien
Belgium	Investigational Site Number 056002	Antwerpen
Belgium	Investigational Site Number 056003	Leuven
Canada	Investigational Site Number 124001	Toronto
France	Investigational Site Number 250001	Marseille
France	Investigational Site Number 250003	Nimes Cedex 9
France	Investigational Site Number 250002	Paris Cedex 10
France	Investigational Site Number 250006	Paris Cedex 12
France	Investigational Site Number 250004	Toulouse
Germany	Investigational Site Number 276003	Frankfurt Am Main
Germany	Investigational Site Number 276007	Leipzig
Germany	Investigational Site Number 276006	Magdeburg
Germany	Investigational Site Number 276001	Mannheim
Germany	Investigational Site Number 276005	Ulm
Italy	Investigational Site Number 380004	Firenze
Italy	Investigational Site Number 380001	Milano
Italy	Investigational Site Number 380002	Roma
Italy	Investigational Site Number 380003	Varese
Netherlands	Investigational Site Number 528002	Amsterdam
Netherlands	Investigational Site Number 528003	Maastricht
Netherlands	Investigational Site Number 528001	Nijmegen
Spain	Investigational Site Number 724001	Barcelona
Spain	Investigational Site Number 724003	Majadahonda
Spain	Investigational Site Number 724002	Salamanca
United Kingdom	Investigational Site Number 826001	London
United States	Investigational Site Number 840010	Ann Arbor	Michigan
United States	Investigational Site Number 840005	Atlanta	Georgia
United States	Investigational Site Number 840013	Baltimore	Maryland
United States	Investigational Site Number 840017	Baltimore	Maryland
United States	Investigational Site Number 840024	Charleston	South Carolina
United States	Investigational Site Number 840014	Chicago	Illinois
United States	Investigational Site Number 840022	Cleveland	Ohio
United States	Investigational Site Number 840002	Houston	Texas
United States	Investigational Site Number 840001	Kansas City	Kansas
United States	Investigational Site Number 840019	Middletown	Ohio
United States	Investigational Site Number 840009	New York	New York
United States	Investigational Site Number 840018	New York	New York
United States	Investigational Site Number 840007	Phoenix	Arizona
United States	Investigational Site Number 840015	Salt Lake City	Utah
United States	Investigational Site Number 840003	San Francisco	California
United States	Investigational Site Number 840004	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  France,  Germany,  Italy,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)		6 months	Yes
Secondary	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		6 months	No
Secondary	Duration of spleen response, measured by MRI (or CT scan in subjects with contraindications for MRI)		6 months	No
Secondary	Proportion of subjects with a =50% reduction in length of spleen by palpation from baseline at the end of Cycle 6		6 months	No
Secondary	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)		6 months	No
Secondary	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)		6 months	No
Secondary	Safety, as assessed by clinical, laboratory, ECG, and vital sign events; graded by the NCI CTCAE v4.03		approximately 5 years	Yes
Secondary	Plasma concentrations of SAR302503		4 months	No
Secondary	The effect of SAR302503 on the JAK2V617F allele burden		2 years	No