Study With SAR302503 in Patients With Polycythemia Vera or Essential Thrombocythemia

Hematopoietic Neoplasm Clinical Trial

Official title: A Randomized Phase II, Open-Label Study of the Efficacy and Safety of Orally Administered SAR302503 in Patients With Polycythemia Vera (PV) or Essential Thrombocythemia (ET) Who Are Resistant or Intolerant to Hydroxyurea

Status Completed

Clinical Trial 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.

Clinical Trial 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. ;

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Hematopoietic Neoplasm
• Polycythemia
• Polycythemia Vera
• Thrombocythemia, Essential
• Thrombocytosis

• NCT number: NCT01420783
• Study type: Interventional
• Source: Sanofi
• Status: Completed
• Phase: Phase 2
• Start date: October 2011
• Completion date: May 2014