Pilot Study of Metformin for Patients With Fanconi Anemia

Status: Recruiting
DFCI Protocol ID:

This is a single institution, open-label, single arm pilot study of Metformin in patients with Fanconi Anemia (FA) and cytopenias with the primary endpoint of hematologic response. This study will also assess safety, tolerability, and the biologic effects of Metformin in patients with FA.

Conducting Institutions:

Children's Hospital Boston, Dana-Farber Cancer Institute

Overall PI:

Akiko Shimamura, MD, Boston Children's Hospital

Site-responsible Investigators:


Dana-Farber Cancer Institute: Childrens Hospital Pediatric Clinical Translation Investigation Program CTIP, ctip@partners.org

Eligibility Criteria

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


• 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

  -  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

  -  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.

Know Your Options

Not sure which clinical trials might be right for your child? Email our clinical trials team at clinicaltrials@danafarberbostonchildrens.org.
We can help you navigate your options.

Get Clinical Trial Updates


Stay informed about Dana-Farber/Boston Children's research efforts, including information on new and current clinical trials. Sign up to receive our email newsletter Advances in Pediatric Hematology/Oncology.

Download Our Clinical Trials

Download a list of our open clinical trials. Check back regularly for updates.