Safety and Efficacy of Metformin for Treatment of Cytopenia in Children and Adolescents With Fanconi Anemia

Prospective interventional open-label non-randomized controlled trial to assess safety and efficacy of metformin in treating cytopenia in children and adolescents with Fanconi Anemia.

Study Overview

• Status: Recruiting
• Conditions: Fanconi Anemia
• Intervention / Treatment: Drug: Metformin

Detailed Description

Fanconi anemia (FA) is a genetic disease characterized by bone marrow failure, cancer susceptibility, and developmental abnormalities. Allogeneic hematopoietic stem cell transplantation offers curative therapy for hematologic complications of FA.

Oxymetholone is commonly used in the management of FA as it improves blood counts, red cells, and platelets. However, its use is limited by its high toxicity profile.

Metformin is a potential agent that reduces levels of both chromosomal radials and breaks in FA cells and increases the size of the hematopoietic stem cell compartment thus reducing cytopenia in patients with FA.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Sara M Makkeyah, MD; Phone Number: +201140105222; Email: smakkeyah@med.asu.edu.eg

Study Locations

• Egypt
  • Alexandria, Egypt
    • Recruiting
    • University of Alexandria
  • Cairo, Egypt, 11566
    • Recruiting
    • Ain Shams University
    • Contact: Sara M Makkeyah, MD; Phone Number: 01140105222; Email: smakkeyah@med.asu.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age: 5 to 18 years
• Patients who are diagnosed with Fanconi anemia based on clinical features and confirmed by increased chromosomal breakage on diepoxybutane (DEB) stress testing.
• Presence of cytopenia (at least one of the following: hemoglobin (Hb) < 10 g/dL, platelet count < 100 x 109/L, or an absolute neutrophil count (ANC) < 1.0 x 109/L
• Patients receiving other therapies e.g., androgens are eligible for enrollment after a one-month washout period before the start of metformin.

Exclusion Criteria:

• Patients who underwent bone marrow transplantation.
• Patients with evidence of myelodysplasia, leukemia, or other concurrent malignancy.
• Patients who have a history of allergic reactions to metformin or similar compounds.
• Patients with a history of symptomatic hypoglycemia over the past year or hypoglycemia < 50 mg/dL on screening and baseline laboratory assessments.
• Patients with type 1 diabetes mellitus.
• Patients with vitamin B12 deficiency.
• Patients with Glucose-6-Phosphate Dehydrogenase deficiency.
• Patients with abnormal Kidney function tests including serum creatinine, elevated liver function tests including live enzymes (ALT or AST > 135 U/L, total bilirubin > 1.5 x upper limit of normal for age, and/or patients with metabolic acidosis (bicarbonate < 17 meq/L on venous blood gases).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metformin group; Patients will receive metformin immediate-release tablets orally for 24 weeks. Starting dose will be 500 mg once daily for all patients and the dose will be increased by 500 mg weekly until the goal dose is achieved (500 mg twice daily for patients < 10 years of age, and 1000 mg twice daily for patients 10 years or older).	Drug: Metformin; Patients will receive metformin immediate-release tablets orally for 24 weeks. Starting dose will be 500 mg once daily for all patients and the dose will be increased by 500 mg weekly until the goal dose is achieved (500 mg twice daily for patients < 10 years of age, and 1000 mg twice daily for patients 10 years or older); Other Names: Glucophage
No Intervention: Other treatment group; Patients will receive supportive treatment as indicated

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hematologic response (erythroid)	Erythroid response (pretreatment, < 11 g/dL): Hgb increase by > 1.5 g/dL or Relevant reduction of units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 wk compared with the pretreatment transfusion number in the previous 8 wk.	24 weeks
Hematologic response (platelets)	Platelet response (pretreatment, < 100x10e9/L): Absolute increase of > 30 x 10e9/L for patients starting with > 20 x 10e9/L platelets or Increase from < 20 x 10e9/L to > 20 x10e9/L and by at least 100%	24 weeks
Hematologic response (Neutrophil count)	Neutrophil response (pretreatment, < 1.0 x 10e9/L): At least 100% increase and an absolute increase > 0.5 x 10e9/L	24 weeks

Collaborators and Investigators

• Sponsor: Ain Shams University

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2022
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: December 27, 2023
• First Submitted That Met QC Criteria: July 20, 2024
• First Posted (Actual): July 25, 2024

Study Record Updates

• Last Update Posted (Actual): July 25, 2024
• Last Update Submitted That Met QC Criteria: July 20, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Kidney Diseases; Urologic Diseases; Bone Marrow Diseases; Hematologic Diseases; Genetic Diseases, Inborn; DNA Repair-Deficiency Disorders; Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Renal Tubular Transport, Inborn Errors; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Anemia; Fanconi Syndrome; Fanconi Anemia; Cytopenia; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: FMASU MD 274/2022

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No