Treatment of Hemoglobin SC Disease With Hydroxyurea (SCYTHE)

SC Youth Treatment With Hydroxyurea Effects

Sickle cell disease (SCD), specifically hemoglobin SC disease (HbSC), is a subtype of sickle cell disease with typically higher hemoglobin and milder or later disease complications. Sickle cell disease is a disorder in which red blood cells (RBCs) are abnormally shaped. This can result in painful episodes, serious infections, and damage to body organs. One medication used to treat sickle cell disease is hydroxyurea.

Hydroxyurea therapy offers significant benefits for infants, children, and adolescents with sickle cell anemia. These include a reduction in the frequency of pain crises and acute chest syndrome (inflammation of the lungs). Hydroxyurea has been given to many HbSC patients but HbSC patients were not included in the large clinical trials used to test hydroxyurea in SCD, so less is known about how HbSC patients respond to hydroxyurea.

The purpose of this research study is to see if hydroxyurea, a medication given to many children with the most common type of sickle cell, those who are homozygous for the sickle mutation (HbSS), helps children who have HbSC. The investigators will see if it helps by giving a questionaire when the medication is started, and then every two months at a clinic visit. The questionaire, called the Pediatric Quality of Life Inventory (PedsQL™) Sickle Cell Disease Module version 3.0, measures quality of life. The investigators will also see how hydroxyurea changes laboratory test numbers, and blood thickness.

Study Overview

• Status: Terminated
• Conditions: Hemoglobin SC Disease
• Intervention / Treatment: Drug: hydroxyurea

Detailed Description

To be eligible to participate in this study, patients must have HbSC disease, have experienced a sickle cell disease related complication, or have a score of 80 or lower on the PedsQL™ Sickle Cell Disease Module version 3.0. This questionnaire will be offered to all patients with HbSC seen in our clinic that consent to this study. If the patient is sexually active, they will be offered birth control. If the patient chooses not to initiate effective birth control, they will be tested at their scheduled vist with a urine pregnancy test. If the patient becomes pregnant they will be removed from the study.

The maximum time patients will be on the study is 12 months after starting hydroxyurea therapy, with an option to participate in a 2 year observation study following the end of the study.

Patients will be assessed in the clinic every two months after starting treatment. Hydroxyurea will be started at 10 mg/kg/day, and increased by 5 mg/kg/day at eight week intervals if needed to reach a maximum tolerated dose (MTD). The most common side effect of the drug is a drop in infection fighting cells, or white blood cells, so the medication will be started at a low dose and the dose will be increased only if it is safe to do so.

Patients will be asked to allow the investigators to review information from their medical records at the start of the study, and throughout the study. If the patient would like to participate in the two year follow-up, their records will be reviewed during that period as well.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosis of HbSC disease
2. Score equal or lower than 80 on the PedsQL™ Sickle Cell Disease Module version 3.0
3. Have experienced a sickle cell disease related complication

Exclusion Criteria:

1. Failure to meet inclusion criteria.
2. Hydroxyurea usage in the last 3 months.
3. Chronic RBC transfusion therapy.
4. Packed red blood cell transfusion in the last 3 months (temporary exclusion).
5. Pregnancy, or refusal to use medically effective birth control if female and sexually active.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hydroxurea; Initiate hydroxyurea at 10 mg/kg daily and escalate hydroxyurea dose by 5 mg/kg/day every 8 weeks up to a maximum dose of 35 mg/kg/day if blood counts meet escalation criteria on at least 2 blood tests over eight weeks prior to dose increase.	Drug: hydroxyurea; Treat symptomatic HbSC patients to MTD on hydroxyurea, and assess for clinical improvement using the PedsQL™ Sickle Cell Disease Module version 3.0 after 6 months at MTD, compared to entrance scores; Other Names: Hydrea; Droxia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in PedsQL SCDM	Mean change in PedsQL™ Sickle Cell Disease Module version 3.0 score after achieving MTD compared with baseline. PedsQL™ Sickle Cell Disease Module version 3.0 scores are on a 100 point scale ranging from 0 to 100 with higher values indicating better quality of life. PedsQL: pediatric qulaity of life	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HVR at 45s-1	Change in hematocrit to viscosity ratio (HVR) at 45s-1 at follow-up versus baseline. This is a measure of oxygen carrying capacity, as a higher hematocrit with lower viscosity indicates ability to deliver oxygen without slowed blood flow due to high viscosity or blood thickness. Higher values are associated with improvement.	up to 7 months
Change in HVR at 225s-1	Change in hematocrit viscosity ratio at 225s	up to 7 months
DRBC	Change in percent dense red blood cells	up to 7 months
Change in HbF	Change in fetal hemaglobin	up to 7 months
Change in MCV	Change in mean corpuscular volume	up to 7 months
Change in MCHC	Change in mean corpuscular hemoglobin concentration	up to 7 months
Change in Hb	Change in hemoglobin	up to 7 months
Change in ARC	Change in absolute reticulocyte count	up to 7 months
Change in ANC	Change in absolute neutrophil count	up to 7 months
Change in LDH	Change in lactate dehydrogenase	up to 7 months
Change in UB Levels	Change in unconjugated bilirubin levels	up to 7 months

Collaborators and Investigators

• Sponsor: Baylor College of Medicine
• Investigators: Principal Investigator: Vivien Sheehan, MD, Baylor College of Medicine

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): February 1, 2017
• Study Completion (Actual): March 31, 2017

Study Registration Dates

• First Submitted: January 8, 2015
• First Submitted That Met QC Criteria: January 8, 2015
• First Posted (Estimate): January 13, 2015

Study Record Updates

• Last Update Posted (Actual): September 9, 2020
• Last Update Submitted That Met QC Criteria: September 8, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: quality of life; hydroxyurea; viscosity; Hemoglobin SC disease; red cell density
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell; Hemoglobin SC Disease; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Antisickling Agents; Hydroxyurea
• Other Study ID Numbers: H-35010 SCYTHE