Therapeutic Response Evaluation and Adherence Trial (TREAT)

NCT02286154 | Active Not Recruiting

• 1 other identifier: CCHMC_TREAT
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Anemia, Sickle Cell

Keywords

Hydroxyurea; Sickle Cell; Pharmacokinetics; dynamics; genomics

Outcome Measures

Primary Outcomes (1)

• Time to Reach Maximum Tolerated Dose (months)

  Time it takes to reach maximum tolerated dose (MTD) of hydroxyurea quantified in months.

  Twelve months

Secondary Outcomes (7)

• Hydroxyurea adherence

  Monthly until MTD then yearly up to ten years

• Neurological function

  Yearly

• Non-invasive Transcranial Cerebral Oximetry

  Monthly until MTD then every six months, up to ten years

• Splenic function

  Annually up to ten years

• Kidney function

  Annually, up to ten years

Study Arms (1)

Hydroxyurea

EXPERIMENTAL

All enrolled participants will receive hydroxyurea, but upon enrollment, participants will be identified as part of the "New Cohort" or "Old Cohort" "New Cohort" participants include those who are not receiving hydroxyurea therapy upon study entry. "Old Cohort" participants include those who are already receiving hydroxyurea therapy upon study entry. New Cohort participants will have starting dose predicted using PK/PD data and Old Cohort participants will continue dosing per clinical guidelines.

Drug: Hydroxyurea

Interventions

Hydroxyurea DRUG

For New Cohort participants, PK/PD data will be used to predict the most effective maximum tolerated dose. Old Cohort participants will receive hydroxyurea escalated to MTD as per local clinical guidelines.

Hydroxyurea

Eligibility Criteria

• Age: 6 Months - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis of sickle cell anemia (HbSS or Hbβ0-thalassemia)
• Age 6 months to 21 years at the time of enrollment
• Clinical decision by patient, family, and healthcare provider to initiate hydroxyurea therapy, including patients who are transitioning from chronic transfusions to hydroxyurea therapy

You may not qualify if:

• \. Family unwillingness to sign informed consent or comply with study treatments

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Related Publications (5)

• 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.

  PMID: 41026975 DERIVED

• 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.

  PMID: 34227124 DERIVED

• 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.

  PMID: 34020272 DERIVED

• 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.

  PMID: 31106898 DERIVED

• 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.

  PMID: 26615061 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Hydroxyurea

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals

Study Officials

• Charles Quinn, MD, MS

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2014
• First Posted: November 7, 2014
• Study Start: October 1, 2014
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: July 17, 2025

Record last verified: 2025-07

Locations

US (1)