IL15 by Continuous Intravenous Infusion to Adult Patients with Solid Tumors in a Phase I Trial Induced Dramatic NK-Cell Subset Expansion.
Cytokines
/ metabolism
Female
Humans
Immunohistochemistry
Immunologic Factors
/ administration & dosage
Immunomodulation
/ drug effects
Inflammation Mediators
/ metabolism
Infusions, Intravenous
Interleukin-15
/ administration & dosage
Killer Cells, Natural
/ drug effects
Lymphocyte Activation
/ drug effects
Lymphocyte Count
Lymphocyte Subsets
/ drug effects
Lymphocytes, Tumor-Infiltrating
/ drug effects
Neoplasms
/ diagnosis
Treatment Outcome
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
15 08 2019
15 08 2019
Historique:
received:
23
10
2018
revised:
26
01
2019
accepted:
17
05
2019
pubmed:
31
5
2019
medline:
20
8
2020
entrez:
31
5
2019
Statut:
ppublish
Résumé
The first-in-human clinical trial with human bolus intravenous infusion IL15 (rhIL15) was limited by treatment-associated toxicity. Here, we report toxicity, immunomodulation, and clinical activity of rhIL15 administered as a 10-day continuous intravenous infusion (CIV) to patients with cancers in a phase I trial. Patients received treatment for 10 days with CIV rhIL15 in doses of 0.125, 0.25, 0.5, 1, 2, or 4 μg/kg/day. Correlative laboratory tests included IL15 pharmacokinetic (PK) analyses, and assessment of changes in lymphocyte subset numbers. Twenty-seven patients were treated with rhIL15; 2 μg/kg/day was identified as the MTD. There were eight serious adverse events including two bleeding events, papilledema, uveitis, pneumonitis, duodenal erosions, and two deaths (one due to likely drug-related gastrointestinal ischemia). Evidence of antitumor effects was observed in several patients, but stable disease was the best response noted. Patients in the 2 μg/kg/day group had a 5.8-fold increase in number of circulating CD8 This phase I trial identified the MTD for CIV rhIL15 and defined a treatment regimen that produced significant expansions of CD8
Identifiants
pubmed: 31142503
pii: 1078-0432.CCR-18-3468
doi: 10.1158/1078-0432.CCR-18-3468
pmc: PMC6697593
mid: NIHMS1043046
doi:
Substances chimiques
Cytokines
0
Immunologic Factors
0
Inflammation Mediators
0
Interleukin-15
0
Banques de données
ClinicalTrials.gov
['NCT01572493']
Types de publication
Clinical Trial, Phase I
Journal Article
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
4945-4954Subventions
Organisme : Intramural NIH HHS
ID : ZIC SC006537-22
Pays : United States
Informations de copyright
©2019 American Association for Cancer Research.
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