SCYTHE: Treatment of Hemoglobin SC Disease With Hydroxyurea

• Sponsor: Baylor College of Medicine (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02336373
• Collaborator: (none)
• Enrollment: 32
• Location: 1
• Arm: 1
• Duration (Months): 28
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Hemoglobin SC Disease	Drug: hydroxyurea	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: SC Youth Treatment With Hydroxyurea Effects
• Study Start Date: Dec 1, 2014
• Actual Primary Completion Date: Feb 1, 2017
• Actual Study Completion Date: Mar 31, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change in PedsQL SCDM [6 months]

   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

Secondary Outcome Measures

1. Change in HVR at 45s-1 [up to 7 months]

   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.

2. Change in HVR at 225s-1 [up to 7 months]

   Change in hematocrit viscosity ratio at 225s

3. DRBC [up to 7 months]

   Change in percent dense red blood cells

4. Change in HbF [up to 7 months]

   Change in fetal hemaglobin

5. Change in MCV [up to 7 months]

   Change in mean corpuscular volume

6. Change in MCHC [up to 7 months]

   Change in mean corpuscular hemoglobin concentration

7. Change in Hb [up to 7 months]

   Change in hemoglobin

8. Change in ARC [up to 7 months]

   Change in absolute reticulocyte count

9. Change in ANC [up to 7 months]

   Change in absolute neutrophil count

10. Change in LDH [up to 7 months]

    Change in lactate dehydrogenase

11. Change in UB Levels [up to 7 months]

    Change in unconjugated bilirubin levels

Eligibility Criteria

Criteria

• Ages Eligible for Study: 5 Years to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Texas Children's Hospital	Houston	Texas	United States	77030

Sponsors and Collaborators

• Baylor College of Medicine

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 8, 2015

More Information

Publications

None provided.

• Responsible Party: Vivien Sheehan, Assistant Professor, Baylor College of Medicine
• ClinicalTrials.gov Identifier: NCT02336373
• Other Study ID Numbers: H-35010 SCYTHE
• First Posted: Jan 13, 2015
• Last Update Posted: Sep 9, 2020
• Last Verified: Sep 1, 2020

• Keywords provided by Vivien Sheehan, Assistant Professor, Baylor College of Medicine: Hemoglobin SC disease; hydroxyurea; quality of life; viscosity; red cell density
• Additional relevant MeSH terms: Hemoglobin SC Disease; Hydroxyurea

Study Results

Participant Flow

Arm/Group Title	Hydroxurea
Arm/Group Description	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. 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
Period Title: Overall Study
STARTED	32
COMPLETED	14
NOT COMPLETED	18

Baseline Characteristics

Arm/Group Title	Hydroxyurea
Arm/Group Description	hydroxyurea (HU) at 10 mg/kg daily
Overall Participants	32
Age (Count of Participants)
<=18 years	32 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	11 (3.5)
Sex: Female, Male (Count of Participants)
Female	13 40.6%
Male	19 59.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 3.1%
Not Hispanic or Latino	31 96.9%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	31 96.9%
White	0 0%
More than one race	1 3.1%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	32 100%
PedsQLTM 3.0 SCD Module score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	54.9 (20.4)

Outcome Measures

1. Primary Outcome

Title	Change in PedsQL SCDM
Description	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
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Participants who achieved MTD of hydroxyureq per protocol with observed PEDSQL scores at 6-months and baseline (study entry).

Arm/Group Title	Hydroxurea
Arm/Group Description	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. 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
Measure Participants	6
Mean (Standard Deviation) [Score on PedsQL 3.0 SCD Module]	5.7 (15.5)

2. Secondary Outcome

Title	Change in HVR at 45s-1
Description	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.
Time Frame	up to 7 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxyurea
Arm/Group Description	Inititiate hydroxyurea and reach MTD
Measure Participants	6
Mean (Standard Deviation) [au]	0.083 (0.72)

3. Secondary Outcome

Title	Change in HVR at 225s-1
Description	Change in hematocrit viscosity ratio at 225s
Time Frame	up to 7 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxyurea
Arm/Group Description	Inititiate hydroxyurea and reach MTD
Measure Participants	6
Mean (Standard Deviation) [au]	0.11 (0.83)

4. Secondary Outcome

Title	DRBC
Description	Change in percent dense red blood cells
Time Frame	up to 7 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxyurea
Arm/Group Description	hydroxyurea (HU) at 10 mg/kg daily
Measure Participants	6
Mean (Standard Deviation) [percentage of dense red blood cells]	1.93 (20.6)

5. Secondary Outcome

Title	Change in HbF
Description	Change in fetal hemaglobin
Time Frame	up to 7 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxyurea
Arm/Group Description	Inititiate hydroxyurea and reach MTD
Measure Participants	6
Mean (Standard Deviation) [percent]	-0.47 (0.94)

6. Secondary Outcome

Title	Change in MCV
Description	Change in mean corpuscular volume
Time Frame	up to 7 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxyurea
Arm/Group Description	Inititiate hydroxyurea and reach MTD
Measure Participants	6
Mean (Standard Deviation) [fL]	-6.2 (2.3)

7. Secondary Outcome

Title	Change in MCHC
Description	Change in mean corpuscular hemoglobin concentration
Time Frame	up to 7 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxyurea
Arm/Group Description	Inititiate hydroxyurea and reach MTD
Measure Participants	6
Mean (Standard Deviation) [percent]	0.33 (0.43)

8. Secondary Outcome

Title	Change in Hb
Description	Change in hemoglobin
Time Frame	up to 7 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxyurea
Arm/Group Description	Inititiate hydroxyurea and reach MTD
Measure Participants	6
Mean (Standard Deviation) [percent]	-0.62 (0.59)

9. Secondary Outcome

Title	Change in ARC
Description	Change in absolute reticulocyte count
Time Frame	up to 7 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxyurea
Arm/Group Description	Inititiate hydroxyurea and reach MTD
Measure Participants	6
Mean (Standard Deviation) [10^3 cells/uL]	0.01 (0.025)

10. Secondary Outcome

Title	Change in ANC
Description	Change in absolute neutrophil count
Time Frame	up to 7 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxyurea
Arm/Group Description	Inititiate hydroxyurea and reach MTD
Measure Participants	6
Mean (Standard Deviation) [10^3 cells/uL]	-0.24 (0.82)

11. Secondary Outcome

Title	Change in LDH
Description	Change in lactate dehydrogenase
Time Frame	up to 7 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxyurea
Arm/Group Description	Inititiate hydroxyurea and reach MTD
Measure Participants	6
Mean (Standard Deviation) [percent]	-21.7 (52.48)

12. Secondary Outcome

Title	Change in UB Levels
Description	Change in unconjugated bilirubin levels
Time Frame	up to 7 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxyurea
Arm/Group Description	Inititiate hydroxyurea and reach MTD
Measure Participants	5
Mean (Standard Deviation) [percent]	-0.1 (0.28)

Adverse Events

Time Frame	1 year
Arm/Group Title	Hydroxurea
Arm/Group Description	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. 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
All Cause Mortality
	Hydroxurea
	Affected / at Risk (%)	# Events
Total	0/32 (0%)
Serious Adverse Events
	Hydroxurea
	Affected / at Risk (%)	# Events
Total	0/32 (0%)
Other (Not Including Serious) Adverse Events
	Hydroxurea
	Affected / at Risk (%)	# Events
Total	0/32 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.