title: Bayesian dose escalation in oncology with sharing of information between patient populations.
abstract: We present a Phase I dose escalation trial design based on a modified continual reassessment method that allows for sharing of information between populations. We describe our approach in the context of a trial for patients with acute lymphoblastic leukemia (ALL) that is currently being conducted. The ALL trial enrolls both adult and pediatric patient populations. Dose escalation and the determination of the maximum tolerated dose (MTD) are performed separately for each population, but to increase efficiency, information about the dose-toxicity curve is shared. Dose escalation rules allow pediatric patients to skip dose levels provided safety has been shown in adults and the dose level is estimated to be safe for pediatric patients. Trial objectives are to efficiently determine the MTD for each population and to minimize the number of pediatric patients required for dose escalation.
authors.affiliation: Berry Consultants, LLC, 4301 Westbank Drive Suite 140 Bldg B, Austin, TX 78746, United States. Electronic address: kristine@berryconsultants.com.
authors.forename: Kristine R
authors.initials: KR
authors.lastname: Broglio
authors.affiliation: Seattle Genetics, Inc., 21823 30th Drive S.E., Bothell, WA 98021, United States. Electronic address: lsandalic@seagen.com.
authors.forename: Larissa
authors.initials: L
authors.lastname: Sandalic
authors.affiliation: Seattle Genetics, Inc., 21823 30th Drive S.E., Bothell, WA 98021, United States. Electronic address: tina.albertson@gmail.com.
authors.forename: Tina
authors.initials: T
authors.lastname: Albertson
authors.affiliation: Berry Consultants, LLC, 4301 Westbank Drive Suite 140 Bldg B, Austin, TX 78746, United States. Electronic address: scott@berryconsultants.com.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Berry
keywords: Adaptive clinical trial; Bayesian; Continual reassessment method; Maximum tolerated dose; Pediatrics; Phase I