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

• Sponsor: Sanofi (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01523171
• Collaborator: (none)
• Enrollment: 97
• Locations: 42
• Arm: 1
• Duration (Months): 24
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0.1

Study Details

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

Condition or Disease	Intervention/Treatment	Phase
Hematopoietic Neoplasm	Drug: SAR302503	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 97 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: Apr 1, 2012
• Actual Primary Completion Date: Apr 1, 2014
• Actual Study Completion Date: Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

1. 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]

Secondary Outcome Measures

1. 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]

2. Duration of spleen response, measured by MRI (or CT scan in subjects with contraindications for MRI) [6 months]

3. Proportion of subjects with a ≥50% reduction in length of spleen by palpation from baseline at the end of Cycle 6 [6 months]

4. 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]

5. 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]

6. Safety, as assessed by clinical, laboratory, ECG, and vital sign events; graded by the NCI CTCAE v4.03 [approximately 5 years]

7. Plasma concentrations of SAR302503 [4 months]

8. The effect of SAR302503 on the JAK2V617F allele burden [2 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number 840007	Phoenix	Arizona	United States	85054
2	Investigational Site Number 840003	San Francisco	California	United States	94143
3	Investigational Site Number 840004	San Francisco	California	United States	94143
4	Investigational Site Number 840005	Atlanta	Georgia	United States	30322
5	Investigational Site Number 840014	Chicago	Illinois	United States	60637
6	Investigational Site Number 840001	Kansas City	Kansas	United States	66160-7321
7	Investigational Site Number 840017	Baltimore	Maryland	United States	21201
8	Investigational Site Number 840013	Baltimore	Maryland	United States	21229
9	Investigational Site Number 840010	Ann Arbor	Michigan	United States	48109-0759
10	Investigational Site Number 840009	New York	New York	United States	10021
11	Investigational Site Number 840018	New York	New York	United States	10032
12	Investigational Site Number 840022	Cleveland	Ohio	United States	44195
13	Investigational Site Number 840019	Middletown	Ohio	United States	45042
14	Investigational Site Number 840024	Charleston	South Carolina	United States	29406
15	Investigational Site Number 840002	Houston	Texas	United States	77030
16	Investigational Site Number 840015	Salt Lake City	Utah	United States	84112-5550
17	Investigational Site Number 040002	Salzburg		Austria	5020
18	Investigational Site Number 040001	Wien		Austria	1090
19	Investigational Site Number 056002	Antwerpen		Belgium	2060
20	Investigational Site Number 056003	Leuven		Belgium	3000
21	Investigational Site Number 124001	Toronto		Canada	M5G 2M9
22	Investigational Site Number 250001	Marseille		France	13273
23	Investigational Site Number 250003	Nimes Cedex 9		France	30029
24	Investigational Site Number 250002	Paris Cedex 10		France	75475
25	Investigational Site Number 250006	Paris Cedex 12		France	75571
26	Investigational Site Number 250004	Toulouse		France	31000
27	Investigational Site Number 276003	Frankfurt Am Main		Germany	60590
28	Investigational Site Number 276007	Leipzig		Germany	04103
29	Investigational Site Number 276006	Magdeburg		Germany	39120
30	Investigational Site Number 276001	Mannheim		Germany	68167
31	Investigational Site Number 276005	Ulm		Germany	89081
32	Investigational Site Number 380004	Firenze		Italy	50134
33	Investigational Site Number 380001	Milano		Italy	20122
34	Investigational Site Number 380002	Roma		Italy	00161
35	Investigational Site Number 380003	Varese		Italy	21100
36	Investigational Site Number 528002	Amsterdam		Netherlands	1081 HV
37	Investigational Site Number 528003	Maastricht		Netherlands	6229 HX
38	Investigational Site Number 528001	Nijmegen		Netherlands	6525 GA
39	Investigational Site Number 724001	Barcelona		Spain	08036
40	Investigational Site Number 724003	Majadahonda		Spain	28222
41	Investigational Site Number 724002	Salamanca		Spain	37007
42	Investigational Site Number 826001	London		United Kingdom	SE1 9RT

Sponsors and Collaborators

• Sanofi

Investigators

• Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT01523171
• Other Study ID Numbers: ARD12181; 2011-005226-21; U1111-1124-0967
• First Posted: Feb 1, 2012
• Last Update Posted: Mar 17, 2016
• Last Verified: Feb 1, 2016

• Additional relevant MeSH terms: Hematologic Neoplasms; Primary Myelofibrosis

Study Results

No Results Posted as of Mar 17, 2016