Pilot Study of Metformin for Patients With Fanconi Anemia

NCT03398824 | Completed Phase 2 Results FDA Drug

• 1 other identifier: IRB-P00026540
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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 also assess safety, tolerability, and the biologic effects of Metformin in patients with FA.

Conditions

Fanconi Anemia

Keywords

Fanconi Anemia; Metformin

Outcome Measures

Primary Outcomes (1)

• Hematologic Response

  Hematologic response is defined by specific increases in erythroid, platelet, and neutrophil counts. Erythroid response: Hemoglobin (Hgb) increase by \>1.5g/dL for non-transfusion dependent patients and for patients who are transfusion dependent: Transfusion independence Only transfusions given for Hgb ≤8g/dL or for symptoms will be counted in the response evaluation Platelet response: If initially \<20k/uL to start, then must increase to \>20k/UL with an absolute increase of 100%. If initially ≥20k/uL to start, then must have an absolute increase of \>30k/UL Neutrophil response: If initially \<500/uL to start, then must increase to \>500/uL with an absolute increase of \> 250/uL. If initially ≥500/uL to start, then must have an absolute increase of \>500/uL

  6 months

Study Arms (1)

Treatment arm

EXPERIMENTAL

Receive metformin HCl

Drug: metformin HCl

Interventions

metformin HCl DRUG

Receive metformin HCl

Treatment arm

Eligibility Criteria

• Age: 6 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Boston Children's Hospital: lead

Study Sites (1)

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• Pollard JA, Furutani E, Liu S, Esrick E, Cohen LE, Bledsoe J, Liu CW, Lu K, de Haro MJR, Surralles J, Malsch M, Kuniholm A, Galvin A, Armant M, Kim AS, Ballotti K, Moreau L, Zhou Y, Babushok D, Boulad F, Carroll C, Hartung H, Hont A, Nakano T, Olson T, Sze SG, Thompson AA, Wlodarski MW, Gu X, Libermann TA, D'Andrea A, Grompe M, Weller E, Shimamura A. Metformin for treatment of cytopenias in children and young adults with Fanconi anemia. Blood Adv. 2022 Jun 28;6(12):3803-3811. doi: 10.1182/bloodadvances.2021006490.

  PMID: 35500223 DERIVED

MeSH Terms

Conditions

Fanconi Anemia

Interventions

Metformin

Condition Hierarchy (Ancestors)

Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Bone Marrow Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Akiko Shimamura
• Organization: Boston Children's Hospital

akiko.shimamura@childrens.harvard.edu

617-919-6946

Study Officials

• Akiko Shimamura, MD, PhD

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Bone Marrow Failure and Myelodysplastic Syndrome Program

Study Record Dates

• First Submitted: December 13, 2017
• First Posted: January 16, 2018
• Study Start: March 29, 2018
• Primary Completion: October 9, 2020
• Study Completion: October 9, 2020
• Last Updated: November 29, 2022
• Results First Posted: November 29, 2022

Record last verified: 2022-11

Locations

US (1)