Ndepth: A Randomized Controlled Trial of a Novel Dose-Prediction Equation to Determine Maximum Tolerated Dose for Hydroxyurea Therapy in Pediatric Patients with Sickle Cell Anemia

• Published in: Blood 2019-11, Vol.134 (Supplement_1), p.2267-2267
• Main Authors: George, Alex, Dinu, Bogdan, Estrada, Norma, Minard, Charles, Hurwitz, Richard L, Mahoney, Donald, Yates, Amber M, Vaughan, Mary, Carmouche, Alaundra, Airewele, Gladstone, Susan, Kirk E, Fasipe, Titilope Adenike, Uwaezuoke, Precious, Ware, Russell E.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2019-127414

Patients on hydroxyurea who achieve maximum tolerated dose (MTD), defined by a target level of mild myelosuppression, may have greater laboratory and clinical benefits than those maintained on a lower dose. MTD is currently determined by gradual dose escalation, a process that often takes six to twelve months. Using data from a previous cohort of pediatric patients escalated to MTD on hydroxyurea, we have developed an equation incorporating baseline serum creatinine, body mass index, and absolute reticulocyte count to predict individualized MTD for patients initiating therapy. The NDEPTH (Novel Dose Escalation to Predict Treatment with Hydroxyurea) study is a prospective, open-label, randomized controlled trial consisting of two treatment arms: a standard arm utilizing a current published dose-escalation protocol for achieving hydroxyurea MTD; and an alternative treatment arm utilizing the dose-prediction equation to determine MTD prior to initiation of treatment. The primary endpoint of the study is time to MTD for each arm. Additional endpoints include analysis of safety and clinical and laboratory response to hydroxyurea therapy We recruited 70 pediatric patients to the study, 68 of whom were randomized equally to the standard and dose-prediction arms of the study. There were no significant differences in baseline characteristics between study participants in the two arms. Twenty-six study participants in the standard arm and 27 in the dose-prediction arm successfully reached MTD. Mean MTD was significantly higher in the dose-prediction arm than the standard arm (27.1 mg/kg vs. 22.6 mg/kg; P