Vitamin D3 Supplementation in Acute Myeloid Leukemia: Pharmacokinetic Study
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 2
- 主要终点
- Changes in 25(OH)-D3 levels after supplementation
研究概览
简要总结
This partially randomized phase II trial studies the side effects and best way to give and best dose of cholecalciferol in treating patients with acute myeloid leukemia (AML) undergoing intensive induction chemotherapy. Cholecalciferol may help improve the outcome of patients with AML undergoing intensive chemotherapy
详细描述
PRIMARY OBJECTIVES: I. To assess patients with regards to changes in 25(OH)-D3 changes after supplementation. II. To develop a pharmacokinetic model to describe the time course of the relationship of vitamin D3 (cholecalciferol) supplementation that drives the levels of 25(OH)-D3 during the intensive induction chemotherapy. III. To determine the safety and toxicity of vitamin D3 supplementation in AML patients undergoing intensive induction chemotherapy. SECONDARY OBJECTIVES: I. To explore whether rapid (loading dose of vitamin D3) normalization of 25(OH)-D3 levels will have an effect on the progression free and overall survival. II. To explore whether a relationship exists between the pharmacokinetics of the 25-hydroxy-vitamin D3 and white blood cell count. OUTLINE: Patients with pretreatment 25(OH)-D3 levels 20-31.9 ng/mL (insufficient levels) are randomized to 1 of 2 treatment arms. ARM I: Patients receive a loading dose of cholecalciferol orally (PO) on day 1. Patients then receive lower-dose cholecalciferol PO beginning on day 8. ARM II: Patients receive a loading dose of cholecalciferol PO on day 1. Patients then receive higher-dose cholecalciferol PO beginning on day 8. Patients with pretreatment 25(OH)-D3 levels < 20 ng/mL (deficient levels) receive a loading dose of cholecalciferol PO on days 1 and 8. Patients then receive lower-dose cholecalciferol PO beginning on day 15. For all patients, treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 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
- •Pathologic diagnosis of newly diagnosed AML (excluding acute promyelocytic leukemia [APL]) Patients undergoing intensive induction therapy (equivalent of 7+3, cytarabine, daunorubicin, etoposide [ADE] or high-dose cytarabine containing regimens) Subnormal 25(OH)-D3 levels (< 32 ng/mL) Serum calcium =< upper limit of normal Demonstrate the ability to swallow and retain oral medication Patients of child-bearing potential must agree to use acceptable contraceptive methods (e.g., double barrier) during treatment Patient or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
排除标准
- •Patients should not have a history of nephrocalcinosis Patients should not have received bisphosphonate treatment within 28 days before study entry Pregnant or nursing female patients Unwilling or unable to follow protocol requirements Any condition which in the Investigator's opinion deems the patient an unsuitable candidate to receive study drug Received an investigational agent within 30 days prior to enrollment Patients who cannot be discontinued from cimetidine, thiazide diuretics and/or heparin Patients who are on magnesium based antacids who cannot be offered an alternative regimen
结局指标
主要结局
Changes in 25(OH)-D3 levels after supplementation
时间窗: From baseline to monthly for the first 3 months and then every 3 months
The within-group pre- and post-supplementation levels will be summarized separately and the within-subject change will also be computed. To assess within-arm treatment effects the sign test will be used.
Pharmacokinetic parameters
时间窗: 30 minutes before administration, 30 minutes after administration, and 24 hours after administration on day 1; monthly for the first 3 months; and then every 3 months
Summarized using the mean (with corresponding 90% confidence intervals) and standard deviation.
Safety and toxicity parameters
时间窗: Daily for 21 days and monthly thereafter, up to 30 days after last dose of study drug
Rates corresponding to toxicity endpoints will be estimated using simple relative frequencies. The corresponding 90% confidence intervals for the estimated probabilities will be computed using the method proposed in Clopper and Pearson. Comparison between groups will be done in an exploratory fashion using appropriate two-sample tests. A nominal significance level of 0.10 will be used in all testing.
次要结局
未报告次要终点