A Phase I/II Clinical Study of JNJ-30979754 (Decitabine) in Patients With Myelodysplastic Syndrome
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 39
- 主要终点
- Phase II: Overall Remission Rate (ORR): Number of Participants Who Achieved Complete Remission (CR)+Partial Remission (PR) - as Per International Working Group (IWG) Response Criteria (2000)
研究概览
简要总结
The purpose of this study is to to determine the recommended dose level of JNJ-30979754 (decitabine) as well as to assess the safety and effectiveness in patients with Myelodysplastic Syndrome (MDS).
详细描述
This is an open-label (both physician and patient know the name and dosage of drug), multi-center study. This study consists of two parts, Phase I and Phase II. In Phase I, approximately 9 participants will be enrolled ie, 3 participants for dose level 1 (15 mg/m2 of JNJ-30979754) and 6 participants for dose level 2 (20 mg/m2 of JNJ-30979754). Once the tolerability of 20 mg/m2 is confirmed additional 30 participants will be included to receive 20 mg/m2 and approximate total participants in Phase II will be 36. This study will include screening period (within 14 days prior to the day of initial administration of Cycle 1) and dosing period (1 cycle consists of administration of study medication for first 5 consecutive days + rested for 23 days; ie, total 28 days). Cycles will be reapeated in participants in whom decitabine was expected to be effective. Safety evaluations will include assessment of adverse events, vital signs, body weight, clinical laboratory tests: hematology, blood biochemistry and urinalysis, cardiopulmonary function tests: ECG, chest X ray and oximeter analysis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Myelodysplastic syndrome (de novo or secondary) fitting any of the recognized French-American-British classifications: refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, chronic myelomonocytic leukemia with white blood cells less than 13,000 /mm3
- •International Prognostic Scoring System (IPSS) greater than or equal to 0.5 (Intermediate-1, Intermediate-2 or high risk) by bone marrow assessment and bone marrow cytogenetics within 28 days before study registration
- •20 years or older
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- •Normal renal and hepatic function
排除标准
- •Acute Myeloid Leukemia (AML) with bone marrow blasts greater than or equal to 30%
- •Participants with a history of high-dose cytarabine (Ara-C) therapy (greater than 1,000 mg/m2/day)
- •Participants administered adrenal cortex hormones or anabolic hormones within 7 days of study initiation
- •Participants who have received a colony stimulating factor (CSF) formulation within 7 days of study initiation
- •Active double cancer
- •Uncontrolled cardiac disease or cognitive heart failure
- •Uncontrolled restrictive or obstructive pulmonary disease
- •Uncontrolled diabetes mellitus
- •Active viral or bacterial infection
- •Known positive serology for Human immunodeficiency virus
研究组 & 干预措施
Phase I: JNJ-30979754 15 mg/m2
JNJ-30979754 (decitabine) 15 mg/m2 will be administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) Cycle 1
干预措施: JNJ-30979754 15 mg/m2 (Drug)
Phase I: JNJ-30979754 20 mg/m2
JNJ-30979754 (decitabine) 20 mg/m2 will be administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) Cycle 1
干预措施: JNJ-30979754 20 mg/m2 (Drug)
Phase II: JNJ-30979754 20 mg/m2
JNJ-30979754 (decitabine) 20 mg/m2 will be administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) cycles
干预措施: JNJ-30979754 20 mg/m2 (Drug)
结局指标
主要结局
Phase II: Overall Remission Rate (ORR): Number of Participants Who Achieved Complete Remission (CR)+Partial Remission (PR) - as Per International Working Group (IWG) Response Criteria (2000)
时间窗: Up to 1 years after the last participant enrolled
IWG response criteria (2000) - CR: bone marrow evaluations show \< 5% blasts; no dysplasia; normal maturation of all cell lines and peripheral blood shows hemoglobin ≥ 11 g/dL; neutrophils ≥ 1,500/mL; platelets ≥ 100,000/mL; 0% blasts; no dysplasia and PR: same as CR, except blasts decrease by ≥ 50% or lower French-American-British (FAB) classification of Myelodysplastic Syndromes.
Phase I and II: Number of Participants Who Experienced Adverse Events
时间窗: Up to 1.5 years after the last participant enrolled
次要结局
- Phase I: Maximum Observed Plasma Concentration of Decitabine (Cmax)(Before dosing (Pre-dose), 30 min, 60 min (end of infusion), 65 min, 75 min, 90 min, 120 min, 180 min, 240 min after the start of decitabine infusion on Day 1 and Day 5 of 28-Days Cycle 1)
- Phase II: Median Duration of Overall Improvement(Up to 1.5 years after the last participant enrolled)
- Phase II: Overall Improvement Rate: Number of Participants Who Achieved Complete Response (CR)+Partial Response (PR)+Hematological Improvement (HI) - as Per International Working Group (IWG) Response Criteria (2000)(Up to 1.5 years after the last participant enrolled)
- Phase I: Area Under the Plasma Concentration-time Curve (AUC)(Before dosing (Pre-dose), 30 min, 60 min (end of infusion), 65 min, 75 min, 90 min, 120 min, 180 min, 240 min after the start of decitabine infusion on Day 1 and Day 5 of 28-Days Cycle 1)
- Phase I: Number of Participants Who Achieved Complete Remission (CR)+Partial Remission (PR)+Hematological Improvement (HI) - as Per International Working Group (IWG) Response Criteria (2000)(Up to 28 Days of treatment Cycle 1)
- Phase II: Median Time to Remission(Up to 1.5 years after the last participant enrolled)
- Phase II: Median Time to Improvement(Up to 1.5 years after the last participant enrolled)
- Phase II: Median Duration of Remission(Up to 1.5 years after the last participant enrolled)
- Phase II: Number of Participants With Cytogenic Response - as Per International Working Group (IWG) Response Criteria 2000 (Major/Minor) and IWG 2006 (Complete/Partial)(Up to 1.5 years after the last participant enrolled)