Quercetin in Children With Fanconi Anemia; a Pilot Study

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.

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