A Phase I, Dose-Ranging Study to Evaluate the Pharmacokinetics and Safety of Azacitidine Administered Subcutaneously (SC) and as Different Oral Formulations in Subjects With Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), Acute Myelogenous Leukemia (AML), Lymphoma, and Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Celgene
- 入组人数
- 31
- 试验地点
- 11
- 主要终点
- To estimate the dose for a given oral formulation that would yield similar exposure [area under the curve (AUC)] to 75 mg/m2 of the subcutaneous formulation.
研究概览
简要总结
The purpose of this study is to compare the amount of drug that gets into the bloodstream between different tablets taken by mouth and an injection under the skin.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 MDS or CMML
- •Diagnosis of AML, Multiple myeloma, Hodgkin's or Non-Hodgkin's lymphoma for whom standard curative or palliative measures do not exist or are no longer effective
- •ECOG Performance Status 0-2
- •Use of acceptable birth control
- •Standard safety inclusion for serum creatinine, AST, ALT, bilirubin
- •Serum bicarbonate greater than or equal to 20 mEq/L
- •Platelet count greater than or equal to 25,000/uL
- •Hemoglobin greater than or equal to 500/uL
- •Signed informed consent
排除标准
- •Diagnosis of acute promyelocytic leukemia
- •Treatment with demethylating agents within 21 days prior to Cycle 1, Day 1
- •Treatment with any anticancer therapy (standard or investigational) within 21 days prior to Cycle 1, Day 1 or ongoing adverse events from previous treatment
- •Hypersensitivity to azacitidine or mannitol
- •Active, uncontrolled infection
- •Presence of GI disease, malignant tumors or other conditions known to interfere with ADME
- •Known or active HIV, viral hepatitis B or C
- •Breastfeeding or pregnant females
- •Current or uncontrolled cardiac disease
研究组 & 干预措施
Arm 1
subcutaneous and oral azacitidine
Cycle 1 (PK Phase) - Subjects will receive a single SC dose of 75 mg/m2 on Days 1 and 15. Single oral doses of a given formulation of azacitidine will be administered in increasing doses on Days 3 and 5, and at doses calculated to deliver 80% and 120% of the SC exposure, up to a maximum dose of 600 mg on Days 17 and 19.
Cycles 2 and beyond - (Treatment phase) Oral azacitidine will be administered in a dose calculated to deliver 100% of the SC exposure up to a maximum of 600 mg on days 1 - 7 of a 28 day cycle.
干预措施: azacitidine (Drug)
Arm 2
Oral Azacitidine
All Cycles - Oral azacitidine will be administered a maximum of 600 mg on Days 1 - 7 of a 28 days cycle.
干预措施: azacitidine (Drug)
结局指标
主要结局
To estimate the dose for a given oral formulation that would yield similar exposure [area under the curve (AUC)] to 75 mg/m2 of the subcutaneous formulation.
时间窗: 1 - 18 months
次要结局
- To determine the oral bioavailability of up to 6 different oral formulations in comparison to the subcutaneous formulation(1 - 18 months)
- To assess the safety and tolerability of subcutaneous and oral formulations of azacitidine(1 - 18 months)
- To assess response rates(1 - 18 months)
- To assess RBC transfusion independence(1 - 18 months)
- To investigate the pharmacokinetics of oral azacitidine(1 -18 months)
- To assess the pharmacodynamic effects of oral azacitidine(1 -18 months)