A Phase 1, Open-label, Dose-Escalation Trial to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Oral Azacitidine in Subjects With Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML) or Acute Myelogenous Leukemia (AML).
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Celgene
- 入组人数
- 133
- 试验地点
- 18
- 主要终点
- Maximum-tolerated dose
研究概览
简要总结
The purpose of this study is to determine whether a tablet form of azacitidine that taken by mouth is safe. This Phase I study will also look at different doses and different treatment schedules in order to better understand the effects (positive and negative) of oral azacitidine on the body and on the disease MDS, AML and CMML.
详细描述
Optional Extension Phase (OEP) to the AZA PH US 2007 CL 005 study which allows subjects who continue to receive oral azacitidine and have stable disease or are demonstrating clinical benefit as assessed by the Investigator, and have consented to participate, may enter the OEP of this study (at their current doses) at the start of their next cycle.
Subjects who are entering the OEP should be discontinued from Part 1 or Part 2 protocol prescribed therapy in the AZA PH US 2007 CL 005 study.
Subjects may continue to receive oral azacitidine in the OEP until they meet the criteria for study discontinuation or oral azacitidine becomes commercially available. Subjects discontinuing from the OEP will have an OEP discontinuation visit 28 days after the last dose of study drug or at study withdrawal.
Primary Objective of OEP is to evaluate long term safety of oral azacitidine.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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 or older.
- •Diagnosis of low or Int-1 risk MDS
- •Low platelet count, and/or low hemoglobin, and/or RBC transfusion-dependent and/or platelet transfusion-dependent
- •ECOG Performance status 0-2
- •Standard safety inclusion for serum creatinine, AST, ALT, bilirubin.
- •Serum bicarbonate greater than or equal to 20 mEq/L.
- •Use of acceptable birth control.
- •Signed, written informed consent.
排除标准
- •Diagnosis of acute PML.
- •Previous or concurrent malignancy.
- •Prior treatment with azacitidine or other demethylating agents.
- •Treatment with any anticancer therapy or investigational drugs within 21 days.
- •Hypersensitivity to azacitidine or mannitol.
- •Presence of GI disease.
- •Active, uncontrolled infection.
- •Known Human Immunodeficiency Virus (HIV) or Hepatitis C, or known active viral Hepatitis B.
- •Breastfeeding or Pregnant females;
- •Presence of serious illness, medical condition, or other medical history which would be likely to interfere with a subject's participation in the study or with the interpretation of the results.
- •Current congestive heart failure (NY Heart Association Class III-IV), unstable angina or angina requiring surgical or medical intervention within 6 months, myocardial infarct within 6 months, or uncontrolled cardiac arrhythmia.
研究组 & 干预措施
Subcutaneous (SC) Azacitidine and Oral Azacitidine
Cycle 1 subjects receive SC Azacitidine for first 7 days of 28 day cycle. For Cycle 2 and beyond subjects receive Oral Azacitidine (experimental) for first 7 days of 28 day cycle.
干预措施: Subcutaneous (SC) Azacitidine (Drug)
Subcutaneous (SC) Azacitidine and Oral Azacitidine
Cycle 1 subjects receive SC Azacitidine for first 7 days of 28 day cycle. For Cycle 2 and beyond subjects receive Oral Azacitidine (experimental) for first 7 days of 28 day cycle.
干预措施: Oral Azacitidine (Drug)
Oral Azacitidine
Subjects receive Oral Azacitidine (experimental) QD or BID for the first 14 or 21 days of 28 day cycle.
干预措施: Oral Azacitidine (Drug)
结局指标
主要结局
Maximum-tolerated dose
时间窗: 60 months
Pharmacodynamic blood and bone marrow samples will be collected and evaluated.
时间窗: 60 months
Safety evaluation as measured by monitoring AEs, dose limiting toxicities, scheduled lab assessments, vital sign measurements, ECGs, & physical exams for study duration. Adverse changes in physical signs/symptoms will be graded according to CTC AE V.3.0.
时间窗: 60 months
次要结局
- Efficacy assessed by evidence of response (MDS subjects) and/or hematologic improvement (MDS subjects) examined using IWG criteria.(60 months)
- Biologically active dose based on safety, PK and PD data.(60 months)