A Prospective, Single-Arm, Trial of Dalbavancin-Based Prophylaxis in Children and Adolescents With High-Risk Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- Bacterial bloodstream infection
研究概览
简要总结
This is a single-arm pilot clinical trial evaluating dalbavancin-based prophylaxis in children and adolescents with acute myeloid leukemia or relapsed lymphoblastic leukemia receiving myelosuppressive chemotherapy.
Primary objective:
- To estimate the rate of bacterial bloodstream infection in pediatric patients with AML or relapsed ALL undergoing chemotherapy receiving dalbavancin-based prophylaxis
Secondary objectives:
- To describe the population pharmacokinetics of every 28 days dalbavancin up to 12 weeks in pediatric patients with AML or relapsed ALL undergoing chemotherapy
- To describe the tolerability of every 28 days dalbavancin prophylaxis in pediatric patients with AML or relapsed ALL undergoing chemotherapy
- To describe the acceptability of every 28 days dalbavancin prophylaxis in pediatric patients with AML or relapsed ALL undergoing chemotherapy
- To estimate the rates of likely bacterial infections, Clostridioides difficile infection, and febrile neutropenia in pediatric patients receiving dalbavancin-based prophylaxis
详细描述
Single-arm, open label, prospective, study with q28 days dalbavancin plus fluoroquinolone (either ciprofloxacin or levofloxacin at the discretion of the treating clinician) for up to 3 doses (12 weeks). Primary outcome will be rate of bacterial bloodstream infection during the first 56 days, with comparison to historical control receiving vancomycin-based prophylaxis (matched St. Jude cohort), or levofloxacin prophylaxis (published data Alexander et al, JAMA, 2018).
Participants will be enrolled, and consent obtained by experienced study staff. Baseline samples, including stool, will be collected within 72 hours after the first dose of dalbavancin. Participants will receive up to 3 doses of q28 days dalbavancin, plus ciprofloxacin or levofloxacin at the discretion of the treating clinician, until 12 weeks or other off study criteria are met. PK samples will be obtained after the first dose of dalbavancin and immediately prior to each subsequent dose. Participants will be monitored for adverse events related to dalbavancin, but adverse events directly related to leukemia or cancer therapy will not be reported.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 25 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged less than or equal to 25 years at enrollment
- •Receiving treatment for AML or relapsed ALL at St. Jude and treatment is expected to cause prolonged (> 7 days) severe neutropenia (ANC < 500/ml)
- •Expected to receive care at St. Jude for at least 56 days following enrollment on the protocol
- •Female participant, greater than or equal to 9 years old, has a documented negative pregnancy test prior to receipt of study drug.
排除标准
- •Allergy to vancomycin, dalbavancin, teicoplanin, levofloxacin or ciprofloxacin (Not including non-anaphylactic vancomycin infusion reaction)
- •Documented past or current infection or colonization with pathogenic bacteria resistant to vancomycin plus either ciprofloxacin or levofloxacin, within the prior 6 months
- •Diagnosed with long QT syndrome
- •Any condition judged by the investigator to put the participant at high risk from participation
- •Suspected or proven active bacterial infection
- •Inability to complete requirements of participation in the study (in the opinion of the investigator)
- •Expected survival <28 days
- •Alkaline phosphatase, alanine transferase or total bilirubin ≥ 3x upper limit of normal for age
- •Estimated glomerular filtration rate (EGFR) <30 mL/minute/1.73 m2
- •Other absolute contraindication to administration of fluoroquinolone antibiotics or dalbavancin
- •Participant is pregnant or breastfeeding a child
研究组 & 干预措施
q28 days dalbavancin plus fluoroquinolone
Dalbavancin given at standard treatment doses once every 28 days in combination with standard of care fluoroquinolone (ciprofloxacin or levofloxacin) prophylaxis.
干预措施: Dalbavancin (Drug)
q28 days dalbavancin plus fluoroquinolone
Dalbavancin given at standard treatment doses once every 28 days in combination with standard of care fluoroquinolone (ciprofloxacin or levofloxacin) prophylaxis.
干预措施: Fluoroquinolone (either ciprofloxacin or levofloxacin at the discretion of the treating clinician) (Drug)
结局指标
主要结局
Bacterial bloodstream infection
时间窗: Day 56
Proportion of evaluable participants with bacterial bloodstream infection with 95% confidence intervals
次要结局
- Tolerability of dalbavancin(Day 56)
- Acceptability of dalbavancin prophylaxis(Day 56)
- Likely bacterial infections, Clostridioides difficile infection, and febrile neutropenia(Day 84)
- Dalbavancin peak plasma concentration (Cmax) - Median and range(Once)
- Dalbavancin trough plasma concentration (Cmin)- Median and range(Up to 3 occasions over 87 days)
- Dalbavancin area under the concentration-time curve - Median and range(Once following first dose)