A Randomized Controlled Study Evaluating the Efficacy and Safety of Pegylated Interferon α-2b in Combination With Ruxolitinib vs. Pegylated Interferon α-2b Monotherapy for Treating Hydroxyurea-resistant/Intolerant Polycythemia Vera
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 94
- 试验地点
- 1
- 主要终点
- The cumulative complete hematologic response (CHR) rate
研究概览
简要总结
Study purpose: To compare the efficacy and safety of pegylated interferon α-2b in combination with ruxolitinib versus pegylated interferon α-2b alone for treating hydroxyurea-resistant or hydroxyurea-intolerant polycythemia vera.
详细描述
Study purpose: To compare the efficacy and safety of pegylated interferon α-2b in combination with ruxolitinib versus pegylated interferon α-2b alone for treating hydroxyurea-resistant or hydroxyurea-intolerant polycythemia vera.
The subjects will be randomly divided into two groups:
pegylated interferon alpha-2b combined with ruxolitinib group: pegylated interferon alpha-2b at a starting dose of 180ug will be administered subcutaneously once a week; ruxolitinib at a starting dose of 10mg will be administered orally twice daily.
pegylated interferon alpha-2b group: pegylated interferon alpha-2b at a starting dose of 180ug will be administered subcutaneously once a week.
If complete hematologic remission is not achieved after 12 weeks of treatment with pegylated interferon alpha-2b alone, the subject may be switched to the pegylated interferon alpha-2b combined with ruxolitinib group. If ruxolitinib is not tolerated, the subject may be switched to the pegylated interferon alpha-2b group alone.
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
- •≥18 years old.
- •Male or Female.
- •Meets the diagnostic criteria for Polycythemia Vera according to WHO-
- •Resistant or intolerant to hydroxyurea (based on the 2013 European LeukemiaNet criteria).
- •Have not previously received interferon preparations or ruxolitinib treatment, or the washout period between the last use of interferon preparations or ruxolitinib and the first use of the study drug should not be less than 4 weeks.
- •Patients with indications for cytoreductive therapy.
- •During screening, female hemoglobin (HGB) ≥10g/dL, male hemoglobin (HGB) ≥11g/dL; neutrophil count ≥1.5×109/L; platelet count ≥100×109/L.
- •Voluntary written informed consent.
排除标准
- •Symptomatic splenomegaly;
- •Contraindications to interferon or ruxolitinib therapy;
- •Severe or significant comorbidities that may affect the participant's ability to participate in the study, as determined by the investigator;
- •History of major organ transplantation;
- •Pregnant or breastfeeding women;
- •History or current diagnosis of autoimmune thyroid disease (patients with controlled hypothyroidism on oral thyroid hormone replacement therapy may be included);
- •Documented evidence of any other autoimmune disease (such as active hepatitis, systemic lupus erythematosus, antiphospholipid antibody syndrome, or autoimmune arthritis);
- •Clinically significant bacterial, fungal, mycobacterial, parasitic, or viral infection such as active hepatitis or HIV infection (patients with acute bacterial infections requiring antibiotic treatment should be deferred from screening/enrollment until completion of antibiotic treatment);
- •Evidence of severe retinopathy or clinically significant ophthalmologic disease (due to diabetes or hypertension);
- •Current clinically significant depression or history of depression, or any suicidal attempt or tendency during screening;
- •Active bleeding or thrombotic complications;
- •History of any malignant tumor within the past 5 years (except for stage 0 chronic lymphocytic leukemia [CLL], cured basal cell carcinoma, squamous cell carcinoma, and superficial melanoma);
- •History of alcohol or substance abuse within the past year;
- •Presence of blasts in the peripheral blood within the past 3 months;
- •Use of any investigational drug or participation in any other clinical trial within 4 weeks prior to the first dose of the study drug, or failure to recover from any effects of previously administered study drugs;
- •The investigator deems the presence of any concurrent condition that may jeopardize the safety of the participant or the compliance to the protocol.
研究组 & 干预措施
pegylated interferon α-2b in combination with ruxolitinib group
Pegylated interferon α-2b in combination with ruxolitinib group: Pegylated interferon α-2b at a starting dose of 180ug, subcutaneous injection once a week; ruxolitinib at a starting dose of 10mg, orally administered twice daily.
干预措施: Ruxolitinib (Drug)
pegylated interferon α-2b in combination with ruxolitinib group
Pegylated interferon α-2b in combination with ruxolitinib group: Pegylated interferon α-2b at a starting dose of 180ug, subcutaneous injection once a week; ruxolitinib at a starting dose of 10mg, orally administered twice daily.
干预措施: Pegylated interferon α-2b (Drug)
Pegylated interferon α-2b group
Pegylated interferon α-2b group: Starting dose of 180ug, subcutaneous injection once a week.
If complete hematological remission is not achieved after 12 weeks of treatment with pegylated interferon α-2b alone, cross-over to the pegylated interferon α-2b plus ruxolitinib group is allowed; if ruxolitinib is not tolerated, cross-over to the pegylated interferon α-2b alone group is allowed.
干预措施: Pegylated interferon α-2b (Drug)
结局指标
主要结局
The cumulative complete hematologic response (CHR) rate
时间窗: From the start of study treatment (Week 0) up to the end of Week 24.
The proportion of patients who can achieve CHR ( defined as hematocrit lower than 45% without phlebotomies; platelet count \< 400×109/L, WBC count \< 10×109/L for at least 12 weeks) among all patients.
次要结局
- Cumulative CHR rates at Week 36.(From the start of study treatment (Week 0) up to the end of Week 36.)
- Change of splenomegaly(From the start of study treatment (Week 0) up to the end of Week 52.])
- The CHR rates after crossover(From the start of study treatment (Week 0) up to the end of Week 52.)
- Impact of therapy on non-driver mutations(From the start of study treatment (Week 0) up to the end of Week 52.)
- Cumulative CHR rates at Week 52.(From the start of study treatment (Week 0) up to the end of Week 52.)
- Time to CHR(From the start of study treatment (Week 0) up to the end of Week 52.)
- Change of bone marrow pathology(From the start of study treatment (Week 0) up to the end of Week 52)
- The incidence of major bleeding events(From the start of study treatment (Week 0) up to the end of Week 52.)
- Specific pre-defined toxicity(From the start of study treatment (Week 0) up to the end of Week 52.)
- The rate of reduction in JAK2V617F, CALR, or MPL gene mutation burden.(From the start of study treatment (Week 0) up to the end of Week 52.)
- The incidence of major thrombotic events(From the start of study treatment (Week 0) up to the end of Week 52.)
- The incidence of progressing to acute leukemia(From the start of study treatment (Week 0) up to the end of Week 52.)
- Change in Myeloproliferative Neoplasm Symptom Assessment Form total symptom score(From the start of study treatment (Week 0) up to the end of Week 52.)
- Change of microcirculation disturbance(From the start of study treatment (Week 0) up to the end of Week 52.)
- Change of quality of life using QLQ-C30 V3.0 questionnaire.(From the start of study treatment (Week 0) up to the end of Week 52.)