Accelerating drug development in pediatric cancer: a novel Phase I study design of venetoclax in relapsed/refractory malignancies.
Venetoclax is a highly selective, potent BCL-2 inhibitor that is approved for some patients previously treated for chronic lymphocytic leukemia, and has shown promising activity in adult studies across several hematologic malignancies. Preclinical studies have demonstrated venetoclax activity in pediatric patient-derived xenograft models and cell lines; however, clinical studies in pediatric patients have yet to be conducted. The prognosis is poor for children with most relapsed/refractory malignancies, and limited treatment options result in unmet clinical need. Herein, we describe the rationale and design of the first study of venetoclax in pediatric patients with relapsed/refractory malignancies: a Phase I trial investigating the safety and pharmacokinetics of venetoclax monotherapy followed by the addition of chemotherapy (Trial registration: EudraCT 2017-000439-14; NCT03236857).
['Place|Andrew E|AE|', 'Goldsmith|Kelly|K|', 'Bourquin|Jean-Pierre|JP|', 'Loh|Mignon L|ML|', 'Gore|Lia|L|', 'Morgenstern|Daniel A|DA|', 'Sanzgiri|Yeshwant|Y|', 'Hoffman|David|D|', 'Zhou|Ying|Y|', 'Ross|Jeremy A|JA|', 'Prine|Betty|B|', 'Shebley|Mohamad|M|', 'McNamee|Megan|M|', 'Farazi|Thalia|T|', 'Kim|Su Young|SY|', 'Verdugo|Maria|M|', 'Lash-Fleming|Leanne|L|', 'Zwaan|C Michel|CM|', 'Vormoor|Josef|J|']
D000367:Age Factors D000970:Antineoplastic Agents D015415:Biomarkers D019086:Bridged Bicyclo Compounds, Heterocyclic D002675:Child, Preschool D002985:Clinical Protocols D000076722:Drug Development D019008:Drug Resistance, Neoplasm D006801:Humans D009369:Neoplasms D012008:Recurrence D012107:Research Design D013449:Sulfonamides D016896:Treatment Outcome
pediatric cancer venetoclax relapsed/refractory BCL-2 ALL AML NHL neuroblastoma