Safety and Efficacy of Metformin for Treatment of Cytopenia in Children and Adolescents With Fanconi Anemia
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Hematologic response (platelets)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 5 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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).
研究组 & 干预措施
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).
干预措施: Metformin (Drug)
结局指标
主要结局
Hematologic response (platelets)
时间窗: 24 weeks
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%
Hematologic response (Neutrophil count)
时间窗: 24 weeks
Neutrophil response (pretreatment, \< 1.0 x 10e9/L): At least 100% increase and an absolute increase \> 0.5 x 10e9/L
Hematologic response (erythroid)
时间窗: 24 weeks
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.
次要结局
未报告次要终点