Quercetin in Children With Fanconi Anemia; a Pilot Study

Fanconi Anemia Clinical Trial

Official title:

Quercetin in Children With Fanconi Anemia; a Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01720147
• Other study ID #: 2011-2049
• Secondary ID: 1R01FD004383-01A
• Status: Completed
• Phase: Phase 1
• Start date: July 2012
• Est. completion date: October 26, 2021

Study information

• Verified date: January 2024
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Fanconi anemia (FA) is an autosomal recessive disease characterized by progressive bone marrow failure (BMF), congenital abnormalities and a predisposition to malignancy.

Description:

Current therapies for children with Fanconi anemia (FA) and bone marrow failure, i.e. androgens or bone marrow transplantation, are associated with significant morbidity and mortality.

This is a pilot study aiming to assess feasibility, toxicity and pharmacokinetics of oral Quercetin therapy in patients with FA. This is a first step towards a clinical study of the efficacy of Quercetin therapy in delaying progression of BMF in FA.

Additional correlative studies will include assessment of impact of Quercetin on reduction of Reactive Oxygen Species (ROS), maintenance or improvement of hematopoietic stem cell (HSC) reserve, improvement of hematopoiesis (i.e. peripheral counts) and insulin sensitivity/glucose tolerance.

This study is an open-label single arm study.

Funding Source - FDA OOPD

Accrual closed for the main study. Expansion cohort added to observe additional patients at the desired dose.

Expansion Cohort:

The second and third cohort of participants completed the study treatment as expected, tolerating Quercetin well without any DLT. Based on the PK and ROS analyses, the dose was increased for the fourth cohort (subjects #10-12). To observe additional patients at the desired dose, an expansion cohort is being added. Up to 20 patients will be enrolled in the expansion cohort. The purpose of the expansion cohort is to assess the effects of quercetin supplement at the desired dose on clinical and biological endpoints.

Patients in the expansion cohort will receive quercetin treatment for the first 26 weeks. Patients will be able to continue quercetin supplement after the completion of the study period of 26 weeks if they wish. If patients decide to continue quercetin after the first 26 weeks, quercetin will be provided by the investigational pharmacy for up to 1 year. Patients who continue quercetin supplement after 26 weeks, but discontinue quercetin before 1 year will be followed through the 1 year visit. Patients who discontinue quercetin supplement any time after the 1 year visit will be followed through the 2 year visit.

Patients previously enrolled in the initial phase of the study (cohorts 1-4) may be considered for enrollment on the expansion cohort of the study provided they meet all inclusion and exclusion criteria.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: October 26, 2021
• Est. primary completion date: October 26, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Diagnosis of FA proven by DEB test or molecular testing

• Able to take enteral medication

• All age groups, including adults

Exclusion Criteria:

• Patients with morphological evidence of myelodysplasia or leukemia

• Renal failure requiring dialysis

• Total bilirubin > 3 mg/dl and/or SGPT >200 at time of enrollment

• Patients who are pregnant or breastfeeding or are at risk of pregnancy and are unable to use acceptable methods of birth control during the length of the study

• Patients receiving cyclosporine or digoxin therapy or are unable to discontinue either treatment due to medical reasons

• Patients who have received quercetin supplementation or other antioxidants within the last 30 days

Related Conditions & MeSH terms

• Anemia
• Fanconi Anemia
• Fanconi Syndrome

Intervention

Drug:
• Quercetin (dietary supplement)
Quercetin will be given orally on a twice a day schedule starting with weight adjusted dose for a maximum total daily dose of 1500 mg/day, for 4 months (16 weeks). Pharmacokinetics (PK) data will be analyzed after each cohort of 3 patients and will be used to optimize the dosing schedule (if required)for subsequent patients. An expansion cohort has been added to the study protocol. Up to 20 patients may be enrolled. The dose utilized will be the same as the max weight adjusted dose that showed biological activity in our last cohort of patients (subjects #10-12 from above).

Locations

Country	Name	City	State
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati	Food and Drug Administration (FDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measure the ability to administer twice daily oral quercetin therapy in patients with Fanconi Anemia (FA).		4 months (16 weeks)
Primary	Measure safety of oral quercetin therapy in patients with FA		4 months (16 weeks)
Primary	To measure pharmacokinetics (PK) of oral quercetin therapy in patients with FA		4 months (16 weeks)
Secondary	To measure the impact of quercetin therapy on reduction of Reactive Oxygen Species (ROS).		4 months (16 weeks) and 1 year
Secondary	Number of participants with improved hematopoiesis.		4 months (16 weeks) and 1 year
Secondary	Measure the preservation of hematopoietic stem cell reserve in patients with FA		4 months (16 weeks) and 1 year
Secondary	To measure the impact of quercetin therapy on changes in insulin sensitivity/glucose tolerance.		4 month (16 weeks) and 1 year