A Multicenter, Randomized, Open-label, Parallel-group, Phase 3 Trial of Subcutaneous Azacitidine Plus Best Supportive Care Versus Conventional Care Regimens Plus Best Supportive Care for the Treatment of Myelodysplastic Syndromes (MDS)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Celgene
- 入组人数
- 358
- 试验地点
- 106
- 主要终点
- Kaplan-Meier Estimates for Median Time to Death From Any Cause
研究概览
简要总结
The purpose of this study is to determine whether patients with high-risk myelodysplastic syndromes (MDS) treated with azacitidine have improved survival compared to conventional care treatments. The study will also assess the effect of treatments on response, duration of response, and transformation to acute myeloid leukemia (AML). The study will continue for 12 months following last patient enrolled.
See study AZA PH GL 2003 CL 001 E for information about the extension to this study.
详细描述
Comparison/Control Interventions offered the physician three options:
- Best supportive care (BSC) alone,
- Low-dose cytarabine subcutaneously for 14 days every 28 to 42 days, or
- Standard chemotherapy administered for induction as a continuous intravenous infusion of cytarabine over 7 days plus an anthracycline (daunorubicin, idarubicin, or mitoxantrone) on Days 1, 2, and 3; and, for those eligible, 1 or 2 consolidation cycles administered as continuous intravenous infusions of cytarabine for 3 to 7 days with the same anthracycline that was used at induction on Days 1 and 2 (each cycle between 28 to 70 days from the start of the previous cycle).
All three options included best supportive care. Neither the experimental group (azacitidine) nor any of the comparison/control options allowed use of erythropoietin.
Duration of Intervention: Patients will be treated until death, withdrawal, unacceptable toxicity or conclusion of the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 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
- •Have a diagnosis of refractory anemia with excess blasts or refractory anemia with excess blasts in transformation according to the French-American-British classification system for myelodysplastic syndromes (MDS) and a relatively high risk of acute myeloid leukemia (AML) transformation, with an International Prognostic Scoring System score of INT-2 or High.
- •Be 18 years of age or older
- •Have a life expectancy of at least 3 months
- •Be unlikely to proceed to bone marrow or stem cell transplantation therapy following remission
- •Have serum bilirubin levels less than or equal to 1.5 times the upper limit of normal range for the laboratory
- •Have serum glutamic-oxaloacetic transaminase (aspartate aminotransferase) or serum glutamic-pyruvic transaminase (alanine aminotransferase) levels less than or equal to 2 times the upper limit of normal (unless these are considered to be related to transfusion-induced secondary hemosiderosis)
- •Have serum creatinine levels less than or equal to 1.5 times the upper limit of normal
排除标准
- •Secondary myelodysplastic syndromes (MDS)
- •Prior treatment with azacitidine;
- •Prior history of acute myeloid leukemia (AML);
- •Malignant disease diagnosed within prior 12 months;
- •Metastatic disease;
- •Hepatic tumors;
- •Radiation, chemotherapy, cytotoxic therapy for non-MDS conditions within prior 12 months;
- •Prior transplantation or cytotoxic therapy to treat MDS;
- •Serious medical illness likely to limit survival to 12 months or less;
- •Treatment with erythropoietin or myeloid growth factors during prior 21 days or androgenic hormones during prior 13 days;
- •Active HIV, viral hepatitis type B or C;
- •Treatment with investigational drugs during prior 30 days;
- •Within the 28-day screening period, documented red cell folate deficiency, as evidenced by red blood cell folate (not serum folate) or vitamin B12 deficiency
研究组 & 干预措施
Azacitidine
Study Drug plus best supportive care. Treatment with erythropoietin was not permitted
干预措施: Azacitidine (Drug)
Conventional Care
Physician choice of low dose cytarabine (plus best supportive care), standard chemotherapy (plus best supportive care) or best supportive care (only). Treatment with erythropoietin was not permitted
干预措施: Physician Choice (Other)
结局指标
主要结局
Kaplan-Meier Estimates for Median Time to Death From Any Cause
时间窗: Day 1 (randomization) to 42 months
Kaplan-Meier estimates for the median months until death from any cause within the intent-to-treat population. Patients surviving at the end of the follow-up period were censored at the date of last contact. If a patient withdrew consent to follow-up or was lost to follow-up, the patient was censored as of the last date of contact.
Number of Participants Who Died
时间窗: 42 months
Count of participants who died during the study
Summary of Subgroup Analyses for Kaplan-Meier Estimates for Time to Death From Any Cause
时间窗: Day 1 (randomization) to 42 months
Kaplan-Meier estimates for the median months until death from any cause within the intent-to-treat population. Patients surviving at the end of the follow-up period were censored at the date of last contact. If a patient withdrew consent to follow-up or was lost to follow-up, the patient was censored as of the last date of contact. Subgroups that were analyzed are age, gender, French-American-British (FAB) classification, World Health Organization (WHO) classification and International Prognostic Scoring System (IPSS) classification.
次要结局
- Kaplan-Meier Estimate for Median Time to Transformation to Acute Myeloid Leukemia (AML) or Death From Any Cause, Whichever Occurred First(Day 1 (randomization) to 42 months)
- Summary of Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Independent at Baseline(Day 1 (randomization) to 42 months)
- Summary of Participants' Platelet Transfusion Status for Participants Who Were Transfusion Dependent at Baseline(Day 1 (randomization) to 42 months)
- Number of Participants in Different Categories of Adverse Experiences During Core Study Period(Day 1 (randomization) to 42 months)
- Kaplan-Meier Estimates for Median Time to Transformation to Acute Myeloid Leukemia (AML)(Day 1 (randomization) to 42 months)
- Summary of Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Dependent at Baseline(Day 1 (randomization) to 42 months)
- Number of Participants Considered Hematologic Responders by Investigator Determinations Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS)(Day 1 to 42 months)
- Number of Participants Showing Hematologic Improvement Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS) Assessed by Independent Review Committee(Day 1 to 42 months)
- Time to Disease Progression, Relapse After Complete or Partial Remission, or Death From Any Cause(Day 1 (randomization) to 42 months)
- Summary of Participants' Platelet Transfusion Status for Participants Who Were Transfusion Independent at Baseline(Day 1 (randomization) to 42 months)
- Duration of Any Hematologic Improvement(Day 1 (randomization) to 42 months)
- Number of Infections Per Treatment Year Requiring Intravenous Antibiotics, Antifungals or Antivirals(Day 1 (randomization) to 42 months)