Status:

COMPLETED

Pilot Study of Metformin for Patients With Fanconi Anemia

Lead Sponsor:

Boston Children's Hospital

Conditions:

Fanconi Anemia

Eligibility:

All Genders

6-35 years

Phase:

PHASE2

Brief Summary

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 als...

Eligibility Criteria

Inclusion

  • 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
  • to \< 2 years 0.6 0.6
  • 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

  • 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.

Key Trial Info

Start Date :

March 29 2018

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

October 9 2020

Estimated Enrollment :

15 Patients enrolled

Trial Details

Trial ID

NCT03398824

Start Date

March 29 2018

End Date

October 9 2020

Last Update

November 29 2022

Active Locations (1)

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Boston Children's Hospital

Boston, Massachusetts, United States, 02115