Effectiveness of Nontraditional Hydroxyurea Algorithms: Novel and Clinical Evaluations (ENHANCE)

Summary

The main reason for this research study is to learn more about hydroxyurea and the treatment of sickle cell anemia (SCA). Hydroxyurea is a medication that has been studied for many years and has been shown to provide benefits for people with SCA. In this research study, the investigators hope to learn more about how to improve the dosing and monitoring of hydroxyurea and learn more about the long-term effects of hydroxyurea over time. Hydroxyurea is usually dosed based only on your weight. Our study will use a new way to select a starting dose that is based on how each patient absorbs hydroxyurea.

Timeline

Start

2024-12-19

Primary completion

2026-12

Completion

2028-12

Publications

• Background Hay SB, Ferchen K, Chetal K, Grimes HL, Salomonis N. The Human Cell Atlas bone marrow single-cell interactive web portal. Exp Hematol. 2018 Dec;68:51-61. doi: 10.1016/j.exphem.2018.09.004. Epub 2018 Sep 21.
• Background Marahatta A, Megaraj V, McGann PT, Ware RE, Setchell KD. Stable-Isotope Dilution HPLC-Electrospray Ionization Tandem Mass Spectrometry Method for Quantifying Hydroxyurea in Dried Blood Samples. Clin Chem. 2016 Dec;62(12):1593-1601. doi: 10.1373/clinchem.2016.263715. Epub 2016 Sep 30.
• Background Vassiliou G. Telomere Length and Clonal Hematopoiesis. N Engl J Med. 2023 Jun 29;388(26):2481-2484. doi: 10.1056/NEJMe2303022. Epub 2023 May 4. No abstract available.
• Background Bowman RL, Busque L, Levine RL. Clonal Hematopoiesis and Evolution to Hematopoietic Malignancies. Cell Stem Cell. 2018 Feb 1;22(2):157-170. doi: 10.1016/j.stem.2018.01.011.
• Background Sankaran VG, Xu J, Orkin SH. Advances in the understanding of haemoglobin switching. Br J Haematol. 2010 Apr;149(2):181-94. doi: 10.1111/j.1365-2141.2010.08105.x. Epub 2010 Mar 1.
• Background Ware RE, Davis BR, Schultz WH, Brown RC, Aygun B, Sarnaik S, Odame I, Fuh B, George A, Owen W, Luchtman-Jones L, Rogers ZR, Hilliard L, Gauger C, Piccone C, Lee MT, Kwiatkowski JL, Jackson S, Miller ST, Roberts C, Heeney MM, Kalfa TA, Nelson S, Imran H, Nottage K, Alvarez O, Rhodes M, Thompson AA, Rothman JA, Helton KJ, Roberts D, Coleman J, Bonner MJ, Kutlar A, Patel N, Wood J, Piller L, Wei P, Luden J, Mortier NA, Stuber SE, Luban NLC, Cohen AR, Pressel S, Adams RJ. Hydroxycarbamide versus chronic transfusion for maintenance of transcranial doppler flow velocities in children with sickle cell anaemia-TCD With Transfusions Changing to Hydroxyurea (TWiTCH): a multicentre, open-label, phase 3, non-inferiority trial. Lancet. 2016 Feb 13;387(10019):661-670. doi: 10.1016/S0140-6736(15)01041-7. Epub 2015 Dec 6.
• Background Hankins JS, Helton KJ, McCarville MB, Li CS, Wang WC, Ware RE. Preservation of spleen and brain function in children with sickle cell anemia treated with hydroxyurea. Pediatr Blood Cancer. 2008 Feb;50(2):293-7. doi: 10.1002/pbc.21271.
• Background Letvin NL, Linch DC, Beardsley GP, McIntyre KW, Nathan DG. Augmentation of fetal-hemoglobin production in anemic monkeys by hydroxyurea. N Engl J Med. 1984 Apr 5;310(14):869-73. doi: 10.1056/NEJM198404053101401.
• Background Platt OS. Hydroxyurea for the treatment of sickle cell anemia. N Engl J Med. 2008 Mar 27;358(13):1362-9. doi: 10.1056/NEJMct0708272. No abstract available.
• Background Ware RE. Optimizing hydroxyurea therapy for sickle cell anemia. Hematology Am Soc Hematol Educ Program. 2015;2015:436-43. doi: 10.1182/asheducation-2015.1.436.
• Background Lanzkron S, Carroll CP, Haywood C Jr. Mortality rates and age at death from sickle cell disease: U.S., 1979-2005. Public Health Rep. 2013 Mar-Apr;128(2):110-6. doi: 10.1177/003335491312800206.
• Background Platt OS, Brambilla DJ, Rosse WF, Milner PF, Castro O, Steinberg MH, Klug PP. Mortality in sickle cell disease. Life expectancy and risk factors for early death. N Engl J Med. 1994 Jun 9;330(23):1639-44. doi: 10.1056/NEJM199406093302303.
• Background Vichinsky E, Hurst D, Earles A, Kleman K, Lubin B. Newborn screening for sickle cell disease: effect on mortality. Pediatrics. 1988 Jun;81(6):749-55.

Drugs

Indications