Study With SAR302503 in Patients With Polycythemia Vera or Essential Thrombocythemia
- Registration Number
- NCT01420783
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
Primary Objective:
* Dose Ranging Phase: To evaluate the efficacy of daily oral doses of 100, 200, and 400 mg SAR302503 in patients with PV and ET who are resistant or intolerant to hydroxyurea (per European LeukemiaNet criteria) for :
* Inducing absence of phlebotomy and a hematocrit below 45% for a minimum of 3 months in patients with polycythemia vera, and
* Reduction of platelet count to ≤400 x 10x9/L for a minimum of 3 months in patients with essential thrombocythemia.
* PV Dose Expansion Phase and ET Dose Ranging Phase (only 600 mg dose group): To evaluate the efficacy of daily oral SAR302503 in patients with PV and ET who are resistant or intolerant to hydroxyurea (per European LeukemiaNet criteria) for:
* Inducing absence of phlebotomy eligibility beginning at Day 1 of Cycle 4 visit and continuing through Day 1 of Cycle 6 visit in patients with PV, and
* Reduction of platelet count to ≤400 x 10x9/L beginning at Day 1 of Cycle 4 visit and continuing through Day 1 of Cycle 6 visit in patients with ET.
Secondary Objectives:
* To evaluate the safety of SAR302503.
* To evaluate the efficacy of SAR302503 in patients with PV who are resistant or intolerant to hydroxyurea for inducing absence of phlebotomy eligibility.
* To evaluate the efficacy of SAR302503 in patients with ET who are resistant or intolerant to hydroxyurea for reduction of platelet counts.
* To evaluate the efficacy of SAR302503 in inducing complete and partial responses beginning at Day 1 of Cycle 6 visit through Cycle 8.
* To evaluate splenic response as measured by spleen volume using MRI or CT.
* To evaluate the pharmacokinetics of SAR302503 after single and repeat doses.
* To evaluate the pharmacodynamics of SAR302503 as measured by changes in JAK2V617F allele burden in patients with JAK2V617F mutation, and STAT3 phosphorylation inhibition.
* To measure improvement in baseline myeloproliferative neoplasm (MPN)-associated symptoms, as well as overall impact on quality of life.
* To measure generic health-related quality of life and utility value using the EuroQol Group (EQ-5DTM) questionnaire.
- Detailed Description
The duration of the study for an individual patient is at least 40 weeks and will include a period to assess eligibility (screening period) of up to 4 weeks (28 days), a treatment period of up to 8, 28-day cycles (32 weeks), and a follow-up visit 30 days following the last administration of study drug. Treatment may continue if the patient is deriving benefit and does not experience disease progression, unacceptable toxicity, or meet other study withdrawal criteria.
Per Protocol Amendment No. 5, accrual of patients with essential thrombocythemia is closed.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 81
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description SAR302503 100 mg SAR302503 once daily X 28 days SAR302503 200 mg SAR302503 once daily X 28 days SAR302503 400 mg SAR302503 once daily X 28 days SAR302503 600 mg SAR302503 once daily X 28 days
- Primary Outcome Measures
Name Time Method ET Dose Ranging Phase (only 600 mg dose group): Proportion of ET patients with a platelet count ≤400 x 10x9/L beginning at Day 1 of Cycle 4 visit and continuing through Day 1 of Cycle 6 visit. 2 years Dose Ranging Phase: Proportion of PV patients with absence of phlebotomy and hematocrit below 45% and proportion of ET patients with a platelet count ≤ 400 x 10x9/L for a minimum of 3 months during the first 8 cycles of therapy. 2 years PV Dose Expansion Phase: Proportion of PV patients with absence of phlebotomy eligibility beginning at Day 1 of Cycle 4 visit and continuing through Day 1 of Cycle 6 visit. 2 years
- Secondary Outcome Measures
Name Time Method Proportion of PV patients with absence of phlebotomy eligibility beginning at Day 1 of Cycle 4 visit through Cycle 8 (for PV dose expansion phase only). 2 years Characterization of clinicohematologic response (CR, PR, and no Response) defined by European LeukemiaNet beginning at Day 1 of Cycle 6 visit through Cycle 8. 2 years Percent change in spleen volume (per Magnetic Resonance Imaging (MRI)) at the end of Cycles 4 and 8 or end of treatment (EOT) relative to baseline. 2 years Response (defined as either a 2-point improvement in or resolution of a symptom present at baseline) at the end of Cycles 1, 4, and 8 or end of treatment (EOT), as measured by the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF). 2 years Proportion of patients with a ≥ 35% reduction in spleen volume (per Magnetic Resonance Imaging (MRI)) at the end of Cycles 4 and 8 or end of treatment (EOT) relative to baseline. 2 years Number of participants who have changes in histological, cytogenetic, and molecular responses in bone marrow. 2 years Characterization of the safety profile of SAR302503, including the frequency, duration, and severity of adverse events graded using the National Cancer Institute (NCI) - CTCAE version 4.03, clinical laboratory parameters, ECG, and vital signs. 2 years Proportion of ET patients with platelet count ≤400 x 10x9/L beginning at Day 1 of Cycle 4 visit and continuing through Cycle 8. 2 years Cumulative Distribution Function of responses between treatment groups at the end of Cycles 1, 4, and 8 or EOT on the MPN-SAF. 2 years To measure generic health-related quality of life and utility values using the EQ-5D questionnaire after completion of 8 cycles of therapy. 2 years For each MPN-associated symptom present at baseline on the MPN-SAF, proportion of patients with resolution of that symptom at the end of Cycles 1, 4, and 8. 2 years
Trial Locations
- Locations (35)
Investigational Site Number 840008
🇺🇸Scottsdale, Arizona, United States
Investigational Site Number 840004
🇺🇸La Jolla, California, United States
Investigational Site Number 840005
🇺🇸Los Angeles, California, United States
Investigational Site Number 840011
🇺🇸Palo Alto, California, United States
Investigational Site Number 840010
🇺🇸Ann Arbor, Michigan, United States
Investigational Site Number 840003
🇺🇸Saint Louis, Missouri, United States
Investigational Site Number 036001
🇦🇺Clayton, Australia
Investigational Site Number 840007
🇺🇸Rochester, Minnesota, United States
Investigational Site Number 840001
🇺🇸Houston, Texas, United States
Investigational Site Number 036002
🇦🇺Kingswood, Australia
Investigational Site Number 036004
🇦🇺Kogarah, Australia
Investigational Site Number 036003
🇦🇺Randwick, Australia
Investigational Site Number 124002
🇨🇦Montreal, Canada
Investigational Site Number 124003
🇨🇦Toronto, Canada
Investigational Site Number 124001
🇨🇦Vancouver, Canada
Investigational Site Number 250004
🇫🇷Brest, France
Investigational Site Number 250003
🇫🇷Marseille, France
Investigational Site Number 250001
🇫🇷Paris Cedex 10, France
Investigational Site Number 276004
🇩🇪Frankfurt Am Main, Germany
Investigational Site Number 276003
🇩🇪Mannheim, Germany
Investigational Site Number 380003
🇮🇹Bologna, Italy
Investigational Site Number 380001
🇮🇹Firenze, Italy
Investigational Site Number 380004
🇮🇹Orbassano, Italy
Investigational Site Number 410001
🇰🇷Seongnam, Korea, Republic of
Investigational Site Number 410003
🇰🇷Seoul, Korea, Republic of
Investigational Site Number 410004
🇰🇷Seoul, Korea, Republic of
Investigational Site Number 410002
🇰🇷Seoul, Korea, Republic of
Investigational Site Number 724004
🇪🇸Badalona, Spain
Investigational Site Number 724001
🇪🇸Barcelona, Spain
Investigational Site Number 724003
🇪🇸Madrid, Spain
Investigational Site Number 724002
🇪🇸Valencia, Spain
Investigational Site Number 826001
🇬🇧Belfast, United Kingdom
Investigational Site Number 826006
🇬🇧Birmingham, United Kingdom
Investigational Site Number 826003
🇬🇧London, United Kingdom
Investigational Site Number 826004
🇬🇧London, United Kingdom