A Prospective Trial of Dalbavancin-Based Prophylaxis in Children and Adolescents With High-Risk Leukemia

Официальное название

A Prospective, Single-Arm, Trial of Dalbavancin-Based Prophylaxis in Children and Adolescents With High-Risk Leukemia

Обзор

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

Подробное описание

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.

Вмешательства

• Препарат Dalbavancin
  3 doses of q28 days dalbavancin (12 weeks).
• Препарат Fluoroquinolone (either ciprofloxacin or levofloxacin at the discretion of the treating clinician)
  28 days dalbavancin plus fluoroquinolone (either ciprofloxacin or levofloxacin at the discretion of the treating clinician) for up to 3 doses (12 weeks).

Первичные конечные точки

• Bacterial bloodstream infection [Срок оценки: Day 56]

Вторичные конечные точки (6)

• Tolerability of dalbavancin [Срок оценки: Day 56]
• Acceptability of dalbavancin prophylaxis [Срок оценки: Day 56]
• Likely bacterial infections, Clostridioides difficile infection, and febrile neutropenia [Срок оценки: Day 84]
• Dalbavancin peak plasma concentration (Cmax) - Median and range [Срок оценки: Once]
• Dalbavancin trough plasma concentration (Cmin)- Median and range [Срок оценки: Up to 3 occasions over 87 days]
• Dalbavancin area under the concentration-time curve - Median and range [Срок оценки: Once following first dose]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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
• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• St. Jude Children's Research Hospital — Memphis

Идентификаторы

NCT: NCT06810583 · DAPHNE

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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