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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 81
- 试验地点
- 35
- 主要终点
- 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.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
SAR302503 100 mg
once daily X 28 days
干预措施: SAR302503 (Drug)
SAR302503 200 mg
once daily X 28 days
干预措施: SAR302503 (Drug)
SAR302503 400 mg
once daily X 28 days
干预措施: SAR302503 (Drug)
SAR302503 600 mg
once daily X 28 days
干预措施: SAR302503 (Drug)
结局指标
主要结局
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.
时间窗: 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.
时间窗: 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.
时间窗: 2 years
次要结局
- 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)