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Safety, pharmacokinetics, and pharmacodynamics of panobinostat in children, adolescents, and young adults with relapsed acute myeloid leukemia
- Source :
- Cancer, vol 126, iss 21
- Publication Year :
- 2020
- Publisher :
- eScholarship, University of California, 2020.
-
Abstract
- BackgroundNovel therapies are urgently needed for pediatric patients with relapsed acute myeloid leukemia (AML).MethodsTo determine whether the histone deacetylase inhibitor panobinostat could be safely given in combination with intensive chemotherapy, a phase 1 trial was performed in which 17 pediatric patients with relapsed or refractory AML received panobinostat (10, 15, or 20 mg/m2 ) before and in combination with fludarabine and cytarabine.ResultsAll dose levels were tolerated, with no dose-limiting toxicities observed at any dose level. Pharmacokinetic studies demonstrated that exposure to panobinostat was proportional to the dose given, with no associations between pharmacokinetic parameters and age, weight, or body surface area. Among the 9 patients who had sufficient (>2%) circulating blasts on which histone acetylation studies could be performed, 7 demonstrated at least 1.5-fold increases in acetylation. Although no patients had a decrease in circulating blasts after single-agent panobinostat, 8 of the 17 patients (47%), including 5 of the 6 patients treated at dose level 3, achieved complete remission. Among the 8 complete responders, 6 (75%) attained negative minimal residual disease status.ConclusionsPanobinostat can be safely administered with chemotherapy and results in increased blast histone acetylation. This suggests that it should be further studied in AML.
- Subjects :
- Adult
Male
Myeloid
Pediatric Research Initiative
Adolescent
Pediatric Cancer
Childhood Leukemia
Clinical Trials and Supportive Activities
Oncology and Carcinogenesis
Acute
acute myeloid leukemia
Young Adult
Rare Diseases
Clinical Research
Panobinostat
Genetics
Humans
Oncology & Carcinogenesis
Child
childhood
Cancer
relapse
Pediatric
Leukemia
Evaluation of treatments and therapeutic interventions
Hematology
Neoplasm Recurrence
Local
6.1 Pharmaceuticals
Public Health and Health Services
Female
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Cancer, vol 126, iss 21
- Accession number :
- edsair.od.......325..48bc09b23e17475e9acf12419c8c9f6c