Fanconi Anemia, Squamous Cell Carcinoma
Conditions
Keywords
Hematopoietic cell transplantation
Brief summary
Fanconi anemia (FA) is an autosomal recessive disease characterized by progressive bone marrow failure, variable congenital abnormalities and a predisposition to malignancy, particularly acute myeloid leukemia (AML) and squamous cell carcinoma (SCC). Improved transplant outcomes are modifying the natural history of Fanconi Anemia. Improved transplant survival, no radiation exposure, and almost no GVHD increases the importance of addressing later SCC even further. The investigators hypothesize that quercetin will prevent or delay the development of SCC and associated complications, there by ameliorating or delaying the need for potentially lethal treatment with chemotherapy and/or radiation therapy for the same. Funding Source - FDA Office of Orphan Products Development (OOPD)
Detailed description
Fanconi anemia (FA) is an autosomal recessive disease characterized by progressive bone marrow failure, variable congenital abnormalities and a predisposition to malignancy, particularly acute myeloid leukemia (AML) and squamous cell carcinoma (SCC). Currently, the only curative treatment option for the hematological complications of FA include hematopoietic cell transplantation (HCT). The investigators hypothesize that quercetin will prevent or delay the development of SCC and associated complications, there by ameliorating or delaying the need for potentially lethal treatment with chemotherapy and/or radiation therapy for the same. This study is an open-label, single arm study. This study will enroll approximately 45 post-HCT patients with FA, and approximately 10 patients with FA without history of HCT. In both groups, patients with or without existing pre-malignant lesions or history of SCC will be allowed to participate, if they wish so and at the discretion of the PI. All patients will be treated with oral quercetin. The investigators will determine the efficacy of Quercetin in reducing buccal micronuclei (a surrogate marker of DNA damage and susceptibility to squamous cell carcinoma due to genomic instability) in post-HCT patients with fanconi anemia (FA).
Interventions
Quercetin will be administered twice daily at an adjusted dose based on weight for a maximum total daily dose of 4000mg/day. If the patient is 70 kg or more, the dose will automatically be assigned at the maximum dose of 4000mg/day.
Sponsors
Children's Hospital Medical Center, Cincinnati
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of FA * Able to take enteral medication * Patients ≥2 years
Exclusion criteria
* Renal failure requiring dialysis * Total bilirubin \>3 mg/dl and/or SGPT \>200 at time of enrollment * Patients receiving digoxin therapy, who are unable to discontinue either treatment due to medical reasons * Patients who are pregnant or breastfeeding or are at risk of pregnancy or fathering a baby and are unable to use acceptable methods of birth control during the length of the study * Patients who have received quercetin supplementation or other antioxidants within the last 30 days * Patients receiving radiation therapy, chemotherapy or immunotherapy for treatment of SCC.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least 20% Reduction of Buccal Micronuclei | 1 year | Efficacy of Quercetin in reducing buccal micronuclei. A 20% reduction in the average total number of micronuclei will be considered a success of the intervention. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORParinda A Mehta, MD
Cincinnati Children's Hosptial Medical Center
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 36 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 44 Participants |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 47 |
| other Total, other adverse events | 10 / 47 |
| serious Total, serious adverse events | 3 / 47 |
Outcome results
None listed