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

NCT06519786 | Unknown Phase 3 DMC

• 1 other identifier: FMASU MD 274/2022
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Fanconi Anemia

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (2)

Metformin group

EXPERIMENTAL

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

Other treatment group

NO INTERVENTION

Patients will receive supportive treatment as indicated

Interventions

Metformin DRUG

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)

Also known as: Glucophage

Metformin group

Eligibility Criteria

• Age: 5 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Ain Shams University: lead

Study Sites (2)

University of Alexandria

Alexandria, Egypt

RECRUITING

Ain Shams University

Cairo, 11566, Egypt

RECRUITING

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

Central Study Contacts

Sara M Makkeyah, MD

CONTACT

+201140105222; smakkeyah@med.asu.edu.eg

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 27, 2023
• First Posted: July 25, 2024
• Study Start: October 5, 2022
• Primary Completion: October 1, 2024
• Study Completion: March 1, 2025
• Last Updated: July 25, 2024

Record last verified: 2023-12

Locations

EG (2)