A Phase 2, Open Label, Dose Regimen Ranging Clinical Study to Determine the Safety and Efficacy of INCB018424 in Patients With Advanced Polycythemia Vera or Essential Thrombocythemia Refractory to Hydroxyurea
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 73
- 主要终点
- Percentage of Polycythemia Vera Participants With a Confirmed Clinical Partial Response (PR) or Complete Response (CR)
研究概览
简要总结
To evaluate the safety and efficacy profile of different treatment regimens of Ruxolitinib (INCB018424) administered to two groups of patients; those with polycythemia vera (PV) and those with essential thrombocythemia (ET). Patients in each group were refractory to hydroxyurea or for whom hydroxyurea is contraindicated.
详细描述
The study consisted of a 2-stage design, which included a dose-ranging phase (during which patients received treatment at their randomized dose) and an expansion phase (after adjustment of dose/regimen to achieve an optimal balance of efficacy and safety). During the dose-ranging phase, patients in each disease group (PV or ET) were randomly assigned in a 1:1:1 ratio independent of each other to receive 1 of 3 treatment regimens with Ruxolitinib, 10 mg twice daily (bid), 25 mg bid, or 50 mg once daily (qd). After patients completed 2 cycles of treatment with Ruxolitinib at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis using their discretion in order to achieve an optimal balance of efficacy and safety. During the expansion phase (ie, after optimization of dose), additional patients with PV or ET were enrolled to receive Ruxolitinib at the dose that was selected upon review of data from the dose-ranging phase. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent.
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
- •Confirmed diagnosis of polycythemia vera or essential thrombocythemia as determined by treating physician
- •Disease refractory to hydroxyurea or for whom treatment with hydroxyurea is contraindicated or have refused further treatment with hydroxyurea due to side effects.
- •Patient meets baseline clinical lab parameters
排除标准
- •Treatment with interferon alpha or anagrelide within 7 days and hydroxyurea within 1 day of starting INCB
- •Patients diagnosed with another malignancy unless the malignancy was cervical intraepithelial neoplasia or basal or squamous cell skin cancer and the patient has been disease free for > 3 years
- •Patients receiving therapy with intermediate or high dose steroids greater than the equivalent of 10 mg prednisone per day
- •Clinically significant cardiac disease (New York Heart Association (NYHA) Class III or IV)
研究组 & 干预措施
Ruxolitinib 10 mg BID
Participants received 10 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent.
干预措施: Ruxolitinib (Drug)
Ruxolitinib 25 mg BID
Participants received 25 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent.
干预措施: Ruxolitinib (Drug)
Ruxolitinib 50 mg QD
Participants received 50 mg Ruxolitinib orally once a day (QD) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent.
干预措施: Ruxolitinib (Drug)
结局指标
主要结局
Percentage of Polycythemia Vera Participants With a Confirmed Clinical Partial Response (PR) or Complete Response (CR)
时间窗: Assessed after 2 cycles (56 days) of treatment on Day 1 of Cycle 3
For a confirmed response all criteria must have been sustained for at least 2 months. CR: * Hematocrit \< 45% in men and \< 42% in women * No phlebotomy for 1 month * No palpable splenomegaly * White blood cells \< 10 x 10\^9/L with normal differential and platelets \< 400 x 10\^9/L * No sustained leucopenia or thrombocytopenia (\>2 weeks) * No systemic PV symptoms (pruritus, night sweats, bone pain, fever, weight loss) PR: * Hematocrit \< 45% in men and \< 42% in women * 50% reduction in phlebotomy requirements from 6 months before treatment started * 50% reduction in palpable splenomegaly
Percentage of Essential Thrombocythemia (ET) Participants With a Confirmed Clinical Partial Response (PR) or Complete Response (CR)
时间窗: Assessed after 2 cycles (56 days) of treatment on Day 1 of Cycle 3.
For a confirmed response all criteria must have been sustained for at least 2 months. Complete Clinical Response: * Platelet count \< 400 x 10\^9/L * White blood cell count \< 10 x 10\^9/L with normal differential and Hematocrit ≤ upper limit of normal * Absence of sustained (\> 2 weeks) anemia or leucopenia based on institutional normal ranges * Absence of systemic ET symptoms (pruritus, bone pain, weakness, night sweats, paresthesias) * Absence of palpable splenomegaly Partial Clinical Response: * Platelet count \< 400 x 10\^9/L * 50% reduction in palpable splenomegaly
次要结局
- Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 24 Weeks(Baseline and Week 24 (Cycle 7, Day 1))
- Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 36 Weeks(Baseline and Week 36 (Cycle 10, Day 1))
- Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 12 Weeks(Baseline and Week 12 (Cycle 4, Day 1))
- Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 4 Weeks(Baseline and 4 weeks (Cycle 2, Day 1))
- Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 24 Weeks(Baseline and 24 weeks (Cycle 7, Day 1))
- Change From Baseline to Week 4 in Polycythemia Vera Symptoms(Baseline and Week 4 (Cycle 2, Day 1))
- Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 36 Weeks(Baseline and 36 weeks (Cycle 10, Day 1))
- Change From Baseline to Week 4 in Essential Thrombocythemia Symptoms(Baseline and Week 4 (Cycle 2, Day 1))
- Change From Baseline to Week 4 in Health-related Quality of Life(Baseline and Week 4 (Cycle 2, Day 1))