Phase III Study of SAR302503 in Intermediate-2 and High Risk Patients With Myelofibrosis

Phase 3

Completed

• Conditions: Hematopoietic Neoplasm
• Interventions: Drug: Placebo; Drug: SAR302503

• Registration Number: NCT01437787
• Lead Sponsor: Bristol-Myers Squibb

Brief Summary

Primary Objective:

* To evaluate the efficacy of daily oral doses of 400 mg or 500 mg of SAR302503 (Investigational Medicinal Product, IMP) compared to placebo in the reduction of spleen volume as determined by magnetic resonance imaging (MRI) (or computed tomography scan in patients with contraindications for MRI).

Secondary Objectives:

* To evaluate the effect on Myelofibrosis (MF)-associated symptoms (key MF symptoms) as measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF) diary.

* To evaluate the Overall Survival of patients treated with either 400 mg/day or 500 mg/day of IMP as compared to placebo.

* To evaluate the Progression Free Survival of patients treated with either 400 mg/day or 500 mg/day of IMP as compared to placebo.

* To evaluate the durability of splenic response.

* To evaluate the safety of IMP.

Detailed Description

The expected duration of a patient's 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 End Of Treatment (EOT) visit, which should be performed at least 30 days following the last administration of IMP or placebo.

Patients who continue to benefit clinically will be allowed to remain on IMP or placebo beyond the 6-month treatment period until the occurrence of disease progression or unacceptable toxicity.

Study Timeline

• Study First Submitted: 2011-09-16
• Study First Submitted QC: 2011-09-20
• Study First Posted: 2011-09-21
• Study Start: 2011-12
• Primary Completion: 2014-06
• Study Completion: 2014-06
• Status Verified: 2015-12
• Disposition First Submitted: 2015-12-08
• Disposition First Submitted QC: 2015-12-08
• Disposition First Posted: 2016-01-08
• Last Update Submitted: 2025-03-03
• Last Update Posted: 2025-03-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 289

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo comparator	Placebo	once daily X 28 days, orally, empty stomach, approximately same time each day
SAR302503 500 mg	SAR302503	once daily X 28 days, orally, empty stomach, approximately same time each day
SAR302503 400 mg	SAR302503	once daily X 28 days, orally, empty stomach, approximately same time each day

Primary Outcome Measures

Name	Time	Method
Response Rate (RR), defined as the proportion of patients who have a ≥35% reduction in volume of spleen size at the end of Cycle 6, and confirmed 4 weeks thereafter	6 months

Secondary Outcome Measures

Name	Time	Method
Proportion of patients who have ≥25% reduction in volume of spleen size at end of Cycle 6, and confirmed 4 weeks thereafter.	6 months
Symptom Response Rate (SRR): Proportion of patients with ≥50% reduction from baseline to the end of Cycle 6 in the total symptom score.	6 months	This assessment will be conducted through the modified MFSAF diary, which will be completed during the week prior to Day 1 of each treatment cycle up to Cycle 6, and during the week prior to the end of Cycle 6.
OS (overall survival) of either 400 mg/day or 500 mg/day of IMP as compared to placebo.	approximately 5 years
PFS (progression free survival) of either 400 mg/day or 500 mg/day of IMP as compared to placebo.	approximately 5 years
Duration of spleen response, measured by MRI (or CT scan in patients with contraindications for MRI.	2 years
Clinical and laboratory events graded by the NCI CTCAE v4.03.	approximately 5 years

Trial Locations

Locations (101)

Investigational Site Number 840013; 🇺🇸 Baton Rouge, Louisiana, United States

Investigational Site Number 840014; 🇺🇸 Scottsdale, Arizona, United States

Investigational Site Number 376002; 🇮🇱 Tel Hashomer, Israel

Investigational Site Number 440001; 🇱🇹 Kaunas, Lithuania

Investigational Site Number 620003; 🇵🇹 Porto, Portugal

Investigational Site Number 643001; 🇷🇺 Moscow, Russian Federation

Investigational Site Number 642002; 🇷🇴 Bucuresti, Romania

Investigational Site Number 643007; 🇷🇺 Volgograd, Russian Federation

Investigational Site Number 840004; 🇺🇸 Houston, Texas, United States

Investigational Site Number 276007; 🇩🇪 Bonn, Germany

Investigational Site Number 348002; 🇭🇺 Budapest, Hungary

Investigational Site Number 840001; 🇺🇸 La Jolla, California, United States

Investigational Site Number 840006; 🇺🇸 Los Angeles, California, United States

Investigational Site Number 840012; 🇺🇸 La Jolla, California, United States

Investigational Site Number 840009; 🇺🇸 Newark, New Jersey, United States

Investigational Site Number 840008; 🇺🇸 Rochester, Minnesota, United States

Investigational Site Number 840002; 🇺🇸 Canton, Ohio, United States

Investigational Site Number 036004; 🇦🇺 Tweed Heads, Australia

Investigational Site Number 036005; 🇦🇺 Herston, Australia

Investigational Site Number 036003; 🇦🇺 Randwick, Australia

Investigational Site Number 040001; 🇦🇹 Wien, Austria

Investigational Site Number 036002; 🇦🇺 Wodonga, Australia

Investigational Site Number 056003; 🇧🇪 Antwerpen, Belgium

Investigational Site Number 076004; 🇧🇷 Porto Alegre, Brazil

Investigational Site Number 056001; 🇧🇪 Leuven, Belgium

Investigational Site Number 124001; 🇨🇦 Montreal, Canada

Investigational Site Number 076002; 🇧🇷 Jau, Brazil

Investigational Site Number 076001; 🇧🇷 Rio De Janeiro, Brazil

Investigational Site Number 124003; 🇨🇦 Montreal, Canada

Investigational Site Number 250006; 🇫🇷 Marseille, France

Investigational Site Number 124002; 🇨🇦 Saint John, Canada

Investigational Site Number 250005; 🇫🇷 Nantes Cedex 01, France

Investigational Site Number 250004; 🇫🇷 Nimes, France

Investigational Site Number 276006; 🇩🇪 Aachen, Germany

Investigational Site Number 250002; 🇫🇷 Pierre Benite Cedex, France

Investigational Site Number 250007; 🇫🇷 Poitiers, France

Investigational Site Number 250003; 🇫🇷 Toulouse, France

Investigational Site Number 276001; 🇩🇪 Mannheim, Germany

Investigational Site Number 276008; 🇩🇪 Dresden, Germany

Investigational Site Number 348006; 🇭🇺 Kecskemét, Hungary

Investigational Site Number 348007; 🇭🇺 Györ, Hungary

Investigational Site Number 348001; 🇭🇺 Debrecen, Hungary

Investigational Site Number 348003; 🇭🇺 Miskolc, Hungary

Investigational Site Number 372002; 🇮🇪 Dublin, Ireland

Investigational Site Number 376003; 🇮🇱 Haifa, Israel

Investigational Site Number 372001; 🇮🇪 Galway, Ireland

Investigational Site Number 380002; 🇮🇹 Bergamo, Italy

Investigational Site Number 380004; 🇮🇹 Firenze, Italy

Investigational Site Number 410002; 🇰🇷 Bundang-Gu, Korea, Republic of

Investigational Site Number 410003; 🇰🇷 Seoul, Korea, Republic of

Investigational Site Number 410005; 🇰🇷 Seoul, Korea, Republic of

Investigational Site Number 410004; 🇰🇷 Seoul, Korea, Republic of

Investigational Site Number 410001; 🇰🇷 Seoul, Korea, Republic of

Investigational Site Number 410007; 🇰🇷 Seoul, Korea, Republic of

Investigational Site Number 440002; 🇱🇹 Klaipeda, Lithuania

Investigational Site Number 484001; 🇲🇽 Queretaro, Mexico

Investigational Site Number 616005; 🇵🇱 Brzozow, Poland

Investigational Site Number 616002; 🇵🇱 Gdansk, Poland

Investigational Site Number 616006; 🇵🇱 Lodz, Poland

Investigational Site Number 616010; 🇵🇱 Warszawa, Poland

Investigational Site Number 616003; 🇵🇱 Wroclaw, Poland

Investigational Site Number 620005; 🇵🇹 Coimbra, Portugal

Investigational Site Number 620004; 🇵🇹 Lisboa, Portugal

Investigational Site Number 620001; 🇵🇹 Lisboa, Portugal

Investigational Site Number 642003; 🇷🇴 Brasov, Romania

Investigational Site Number 642004; 🇷🇴 Bucharest, Romania

Investigational Site Number 642006; 🇷🇴 Bucuresti, Romania

Investigational Site Number 643009; 🇷🇺 Moscow, Russian Federation

Investigational Site Number 642001; 🇷🇴 Timisoara, Romania

Investigational Site Number 643008; 🇷🇺 Petrozavodsk, Russian Federation

Investigational Site Number 643004; 🇷🇺 St-Petersburg, Russian Federation

Investigational Site Number 643010; 🇷🇺 Nizhny Novgorod, Russian Federation

Investigational Site Number 643005; 🇷🇺 St.-Petersburg, Russian Federation

Investigational Site Number 702002; 🇸🇬 Singapore, Singapore

Investigational Site Number 702001; 🇸🇬 Singapore, Singapore

Investigational Site Number 710003; 🇿🇦 Johannesburg, South Africa

Investigational Site Number 724001; 🇪🇸 Barcelona, Spain

Investigational Site Number 710002; 🇿🇦 Parktown, South Africa

Investigational Site Number 724002; 🇪🇸 Madrid, Spain

Investigational Site Number 158002; 🇨🇳 Changhua, Taiwan

Investigational Site Number 752001; 🇸🇪 Stockholm, Sweden

Investigational Site Number 158003; 🇨🇳 Kaohsiung, Taiwan

Investigational Site Number 752002; 🇸🇪 Uddevalla, Sweden

Investigational Site Number 158001; 🇨🇳 Taipei, Taiwan

Investigational Site Number 826006; 🇬🇧 Belfast, United Kingdom

Investigational Site Number 826007; 🇬🇧 Manchester, United Kingdom

Investigational Site Number 826002; 🇬🇧 Glasgow, United Kingdom

Investigational Site Number 826001; 🇬🇧 London, United Kingdom

Investigational Site Number 826004; 🇬🇧 Leeds, United Kingdom

Investigational Site Number 826005; 🇬🇧 London, United Kingdom

Investigational Site Number 380007; 🇮🇹 Bologna, Italy

Investigational Site Number 380001; 🇮🇹 Pavia, Italy

Investigational Site Number 380006; 🇮🇹 Pavia, Italy

Investigational Site Number 380003; 🇮🇹 Varese, Italy

Investigational Site Number 250001; 🇫🇷 Villejuif Cedex, France

Investigational Site Number 826003; 🇬🇧 Birmingham, United Kingdom

Investigational Site Number 826008; 🇬🇧 Newcastle Upon Tyne, United Kingdom

Investigational Site Number 826009; 🇬🇧 Oxford, United Kingdom

Investigational Site Number 826010; 🇬🇧 Southampton, United Kingdom

Investigational Site Number 410006; 🇰🇷 Seoul, Korea, Republic of

Investigational Site Number 036001; 🇦🇺 Box Hill, Australia