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

Ain Shams University

Status and phase: Enrolling; Phase 3

Conditions: Fanconi Anemia

Treatments: Drug: Metformin

Study type: Interventional

Funder types: Other

Identifiers

NCT06519786

FMASU MD 274/2022

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 estimated patients

Sex: All

Ages: 5 to 18 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Supportive Care

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

30 participants in 2 patient groups

Metformin group

Experimental group

Description:

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).

Treatment:

Drug: Metformin

Other treatment group

No Intervention group

Description:

Patients will receive supportive treatment as indicated