Acute Myeloid Leukemia, Leukemia, Lymphoblastic Leukemia in Children
Conditions
Brief summary
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
Detailed description
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.
Interventions
DRUGDalbavancin
3 doses of q28 days dalbavancin (12 weeks).
DRUGFluoroquinolone (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).
Sponsors
St. Jude Children's Research Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 25 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bacterial bloodstream infection | Day 56 | Proportion of evaluable participants with bacterial bloodstream infection with 95% confidence intervals |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tolerability of dalbavancin | Day 56 | Proportion of evaluable participants with adverse events attributable to dalbavancin with 95% confidence intervals |
| Acceptability of dalbavancin prophylaxis | Day 56 | Median and range of TSQM II results |
| Likely bacterial infections, Clostridioides difficile infection, and febrile neutropenia | Day 84 | Proportion of evaluable participants with likely bacterial infections, Clostridioides difficile infection, or febrile neutropenia, with 95% confidence intervals |
| Dalbavancin peak plasma concentration (Cmax) - Median and range | Once | Peak concentration of dalbavancin 30-60 minutes after completion of dose administration |
| Dalbavancin trough plasma concentration (Cmin)- Median and range | Up to 3 occasions over 87 days | Trough concentration of dalbavancin 25-31 days after dose administration |
| Dalbavancin area under the concentration-time curve - Median and range | Once following first dose | Estimated area under dalbavancin concentration-time curve |
Countries
United States
Contacts
CONTACTJoshua Wolf, MBBS
PRINCIPAL_INVESTIGATORJoshua Wolf, MBBS
St. Jude Children's Research Hospital
Outcome results
None listed