ArticleClinical trials (London, England)2021
Adapting isotonic dose-finding to a dynamic set of drug combinations with application to a phase I leukemia trial.
Article in Clinical trials (London, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
1 citing paper in PubMed.
- Isotonic Phase I cancer clinical trial design utilizing patient-reported outcomes.Statistics in biopharmaceutical research · 2025Article
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Authors and funding
5 authors.
Funding
Abstract
BACKGROUND/
aimsThis article describes the proposed design of a phase I study evaluating the safety of ceramide nanoliposome and vinblastine among an initial set of 19 possible dose combinations in patients with relapsed/refractory acute myeloid leukemia and patients with untreated acute myeloid leukemia who are not candidates for intensive induction chemotherapy.
methodsExtensive collaboration between statisticians and clinical investigators revealed the need to incorporate several adaptive features into the design, including the flexibility of adding or eliminating certain dose combinations based on safety criteria applied to multiple dose pairs. During the design stage, additional dose levels of vinblastine were added, increasing the dimension of the drug combination space and thus the complexity of the problem. Increased complexity made application of existing drug combination dose-finding methods unsuitable in their current form.
resultsOur solution to these challenges was to adapt a method based on isotonic regression to meet the research objectives of the study. Application of this adapted method is described herein, and a simulation study of the design's operating characteristics is conducted.
conclusionThe aim of this article is to bring to light examples of novel design applications as a means of augmenting the implementation of innovative designs in the future and to demonstrate the flexibility of adaptive designs in satisfying changing design conditions.
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