Hydroxyurea Management in Kids: Intensive Versus Stable Dosage Strategies

NCT03020615 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: HUGKISSR34HL127162
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 4

Brief Summary

This is a pilot study, single-blind, randomized, multicenter, therapeutic clinical trial designed to evaluate the feasibility of enrolling infants and toddlers (9 months to 36 months) with sickle cell anemia (SCA; HbSS or HbSβ\^0thalassemia), regardless of disease severity, to a therapeutic trial. A prior clinical trial at St. Jude Children's Research Hospital (SJCRH) (BABYHUG, NCT01783990) demonstrated that a fixed dose (20 mg/kg/day) of hydroxyurea was safe and effective in decreasing SCA-related complications in very young children (9-18 months), and largely due to these findings, hydroxyurea is recommended to be offered to all children (≥9 months old) with SCA, independent of disease severity. Nevertheless, children in the treatment arm of BABYHUG continued to experience vaso-occlusive symptoms and to incur organ damage. In clinical trials of older children with SCA, intensification of hydroxyurea to a maximum tolerated dosage (MTD), defined by mild to moderate myelosuppression, may be associated with improved laboratory parameters compared to fixed lower-dosing, but the clinical benefits gained from dose intensification have not been described. Therefore, in this trial, children in the standard treatment arm will receive a fixed dose of hydroxyurea (20 mg/kg/day), and participants in the experimental arm will receive hydroxyurea intensified to MTD, defined by a goal absolute neutrophil count (ANC) of 1500-3000 cells/µL. This trial aims to establish a multicenter infrastructure that will identify, enroll and randomize very young children (9-36 months) to receive fixed dose versus intensified-dose hydroxyurea in a single blinded manner, and to obtain prospective pilot data comparing the clinical and laboratory outcomes between the treatment arms to facilitate design of a definitive phase III trial.

Conditions

Sickle Cell Anemia

Keywords

Sickle cell; Hydroxyurea; Infants

Outcome Measures

Primary Outcomes (4)

• Number of Patients Enrolled.

  A count of the number of patients enrolled will be provided.

  at baseline

• Number of Patients Randomized

  A count of the number of patients randomized will be provided.

  Eight weeks (± 2 weeks) after study enrollment

• Number of Randomized Patients With ≥80% Chronic Medication Compliance

  Chronic medication compliance is defined based on medication possession ratio (MPR), a measure of the percentage of time that a patient has access to medication. Each participant's MPR is calculated as \[(days medication in family's possession/days prescribed medication) \* 100\].

  At completion of therapy, up to 56 weeks after study enrollment

• Number of Patients Who Have the % Fetal Hemoglobin (%HbF) Collected at Baseline and at Study Exit

  The number of patients who have successfully provided %HbF at baseline and study exit will be provided.

  At baseline and at completion of the protocol, up to 56 weeks after study enrollment

Secondary Outcomes (35)

• Frequency by Reason Given for Refusal for Study Participation

  Once, at enrollment

• Number of Patients With Hospitalizations by Arm

  From baseline through completion of therapy, up to 56 weeks

• Cumulative Number of Hospitalizations by Arms

  From baseline through completion of therapy, up to 56 weeks

• Mean Change in Hemoglobin (g/dL)

  From baseline at study entry to completion of therapy, up to 56 weeks

• Median Change in Hemoglobin (g/dL)

  From baseline at study entry to completion of therapy, up to 56 weeks

Study Arms (2)

Stable Dosing

ACTIVE COMPARATOR

In the first 8 weeks (± 2 weeks) of this study, participants will receive standard treatment \[a fixed dose of 20 (± 2.5) mg/kg/day of hydroxyurea\]. After 8 weeks (± 2 weeks) of standard treatment, participants will be randomized (like flipping a coin) to one of two treatment groups. Group 1 (Stable Dosing) continues standard treatment.

Drug: Hydroxyurea

Intensive Dosing

EXPERIMENTAL

In the first 8 weeks (± 2 weeks) of this study, participants will receive standard treatment \[a fixed dose of 20 (± 2.5) mg/kg/day of hydroxyurea\]. After 8 weeks (± 2 weeks) of standard treatment, participants will be randomized (like flipping a coin) to one of two treatment groups. Group 2 (Intensive Dosing) will have their HU dose increased by 5 mg/kg/day every 8 weeks up to a maximum of 35 mg/kg/day.

Drug: Hydroxyurea

Interventions

Hydroxyurea DRUG

Given orally once daily.

Also known as: HU

Intensive Dosing; Stable Dosing

Eligibility Criteria

• Age: 9 Months - 36 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Children with HbSS or sickle hemoglobin (HbS)/β\^0thalassemia
• ≥9 to ≤ 36 months of age at study initiation
• Enrollment will occur irrespective of clinical severity

You may not qualify if:

• Permanent:
• Receiving chronic red blood cell transfusion therapy.
• Condition or chronic illness, which in the opinion of the PI makes participation unsafe.
• Transient (participants may be re-evaluated after ≥14 days):
• Recent (\<30 days) participation in another clinical intervention trial utilizing an investigational new drug/investigational device exemption (IND/IDE) agent.
• Erythrocyte transfusion in the past 2 months.
• Laboratory Assessments:
• Hemoglobin \<6.0 g/dL
• Absolute reticulocyte count \<80 \* 10\^3/µL if hemoglobin \<9.0 mg/dL
• Absolute neutrophil count \<1.5 \* 10\^3/µL
• Platelet count \<100 \* 10\^3/µL
• Serum creatinine \> twice the upper limit of normal for age
• Alanine aminotransferase (ALT) \> twice the upper limit of normal

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (4)

Emory University/Children's Health Care of Atlanta

Atlanta, Georgia, 30322, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75390-9063, United States

Location

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

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

Results Point of Contact

• Title: Jeremie Estepp, MD
• Organization: St. Jude Children's Research Hospital

jeremie.estepp@stjude.org

(901) 595-5703

Study Officials

• Jeremie Estepp, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2017
• First Posted: January 13, 2017
• Study Start: May 12, 2017
• Primary Completion: June 8, 2020
• Study Completion: June 8, 2020
• Last Updated: June 25, 2021
• Results First Posted: June 25, 2021

Record last verified: 2021-05

Locations

US (4)