Pilot Study of Metformin for Patients With Fanconi Anemia

Inclusion Criteria:

* Age \> 6 years and ≤35 years
* Lansky/Karnofsky performance status ≥ 50% for patients ≥16 years of age and Lansky ≥ 50% for patients \<16 years of age (see Appendix A)
* Diagnosis requirement
* Participants must have a clinical diagnosis of Fanconi Anemia.

* Participants must have confirmed diepoxybutane-mitomycin C (DEB/MMC) stress testing to document diagnosis of Fanconi Anemia.
* Patients must have at least one of the following cytopenias: Hemoglobin \<10g/dL; Platelets \<100k/uL; Absolute neutrophil count \<1000/uL
* Participants must have normal organ function as defined below:

* Hepatic Function : Total bilirubin ≤ 1.5 x upper limit of normal for age; alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 135 U/L
* Renal Function: A serum creatinine based on age/gender as follows:

Age Maximum Serum Creatinine (mg/dL) Male Female

1. to \< 2 years 0.6 0.6
2. to \< 6 years 0.8 0.8

6 to \< 10 years 1 1 10 to \< 13 years 1.2 1.2 13 to \< 16 years 1.5 1.4

≥ 16 years 1.7 1.4

AND

• Creatinine clearance ≥ 60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal

* Normal cardiac status as documented clinically, otherwise they will need an echocardiogram prior to enrollment
* Serum bicarbonate must be \>17.
* Participants of child-bearing or child-fathering potential must agree to use adequate contraception (hormonal birth control; intrauterine device; double barrier method; or total abstinence) throughout their participation, including up until 30 days after last dose of Metformin.
* Patients must be able to swallow pills.
* Ability to understand and/or the willingness of the patient (or parent or legally authorized representative, if minor) to provide informed consent, documented using an institutionally approved informed consent procedure

Exclusion Criteria:

* Patients must not have undergone prior bone marrow transplantation.
* Patients must not have very severe aplastic anemia at the time of enrollment which would require bone marrow transplantation (as defined by at least 2 out of the following 3: Absolute Neutrophil Count (ANC) \<200k/uL, platelets \<20k/uL, absolute reticulocyte count \<40k/uL).
* Patients must not be taking any other concurrent medications to improve their hematopoiesis such as androgens or growth factors such as Granulocyte colony-stimulating factor (G-CSF), erythropoietin (EPO), or thrombopoietin (TPO) mimetics. There is a one month wash-out period for prior therapies including androgens.
* Pregnant participants will not be entered on this study given that the effects of Metformin on the developing human fetus are unknown.
* Breastfeeding mothers are not eligible because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Metformin.
* Patients must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to Metformin.
* Patients must not have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Patients must not have prior history of symptomatic hypoglycemia over the past year or hypoglycemia with glucose \<50mg/dL on screening and baseline laboratory assessments.
* Patients must not have type 1 diabetes mellitus.
* Patients must abstain from alcohol as part of this study.
* Patients must not have a diagnosis of myelodysplastic syndrome or leukemia, or other concurrent malignancy undergoing treatment.
* Patients must not have vitamin B12 deficiency.
* Patients must not have Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency.

For more information on this trial, visit clinicaltrials.gov.