Therapeutic Response Evaluation and Adherence Trial (TREAT)

Summary

The primary objectives of this prospective study of hydroxyurea for children with sickle cell anemia are 1) Develop and prospectively evaluate a population pharmacokinetic/pharmacodynamics model to predict the maximum tolerated dose (MTD); 2) Identify urine biomarkers of hydroxyurea adherence using a novel metabolomics approach; 3) Identify pharmacogenomics modifiers of hydroxyurea MTD; and 4) Longitudinal monitoring of the effect of hydroxyurea upon organ function and quality of life.

Timeline

Start

2014-10

Primary completion

2026-12

Completion

2026-12

Publications

• Power-Hays A, McElhinney KE, Williams TN, Mochamah G, Olupot-Olupot P, Paasi G, Reid ME, Rankine-Mullings AE, Opoka RO, John CC, McGann PT, Quinn CT, Punt NC, Smart LR, Stuber SE, Latham TS, Vinks AA, Ware RE. Hydroxyurea pharmacokinetics in children with sickle cell anemia across different global populations. Blood Adv. 2026 Jan 27;10(2):418-427. doi: 10.1182/bloodadvances.2025017254.
• Quinn CT, Niss O, Dong M, Pfeiffer A, Korpik J, Reynaud M, Bonar H, Kalfa TA, Smart LR, Malik P, Ware RE, Vinks AA, McGann PT. Early initiation of hydroxyurea (hydroxycarbamide) using individualised, pharmacokinetics-guided dosing can produce sustained and nearly pancellular expression of fetal haemoglobin in children with sickle cell anaemia. Br J Haematol. 2021 Aug;194(3):617-625. doi: 10.1111/bjh.17663. Epub 2021 Jul 5.
• Sadaf A, Quinn CT, Korpik JB, Pfeiffer A, Reynaud M, Niss O, Malik P, Ware RE, Kalfa TA, McGann PT. Rapid and automated quantitation of dense red blood cells: A robust biomarker of hydroxyurea treatment response. Blood Cells Mol Dis. 2021 Sep;90:102576. doi: 10.1016/j.bcmd.2021.102576. Epub 2021 May 11. No abstract available.
• McGann PT, Niss O, Dong M, Marahatta A, Howard TA, Mizuno T, Lane A, Kalfa TA, Malik P, Quinn CT, Ware RE, Vinks AA. Robust clinical and laboratory response to hydroxyurea using pharmacokinetically guided dosing for young children with sickle cell anemia. Am J Hematol. 2019 Aug;94(8):871-879. doi: 10.1002/ajh.25510. Epub 2019 Jun 12.
• Dong M, McGann PT, Mizuno T, Ware RE, Vinks AA. Development of a pharmacokinetic-guided dose individualization strategy for hydroxyurea treatment in children with sickle cell anaemia. Br J Clin Pharmacol. 2016 Apr;81(4):742-52. doi: 10.1111/bcp.12851. Epub 2016 Feb 5.

Drugs

Indications