An open-label, phase II study to assess the efficacy and safety of eltrombopag for the treatment of children and adolescents with Fanconi anemia.

Open-label, phase II study to assess the efficacy and safety of eltrombopag in the treatment of patients diagnosed with Fanconi anemia who have no immediate curative treatment for their bone marrow failure (n=10). The primary objective of this open-label, phase II proof of concept study is to assess the efficacy and safety of using eltrombopag for the treatment of patients with FA before conducting a larger phase II/III study.

Specific objectives:

• Primary: To assess the efficacy of eltrombopag on hematopoiesis by measuring changes in peripheral platelet, hemoglobin and neutrophil counts.
• Secondary: To assess the safety of eltrombopag in patients with Fanconi anemia. If the preliminary efficacy and safety results from the study are positive, we will propose its expansion to a multi-institutional Phase II/III study within the framework of the Spanish Fanconi Anemia Research Network.

Inclusion Criteria:

• Patients with a diagnosis of Fanconi anemia. Diagnosis will be defined by the presence of biallelic mutations in genes known to cause the disease and/or by positive chromosome breakage analysis of lymphocytes and/or skin fibroblasts (for cases of mosaicism).
• Age from 4 to ≤ 17 years.
• Lansky index > 80%.
• Informed consent provided in accordance with current legislation.
• Presenting with one or more of one of the following clinically significant cytopenias:

platelet count ≤ 50x109/L or transfusion dependence, having required at least 2 transfusions in the 8 weeks prior to inclusion in the study; granulocyte count < 0.75x109/L; hemoglobin < 9 gr/dL or transfusion-dependent anemia having received 2 transfusions in the 8 weeks prior to inclusion in the study.

Exclusion Criteria:

• Patients with HLA-matched related donor or unrelated donor with a 12/12 match who is immediately available.
• Evidence of myelodysplastic syndrome or leukemia or cytogenetic abnormalities predictive of these disorders in bone marrow aspirates. In the event, the evaluations performed two months before patient inclusion in the clinical study will be considered valid.
• Baseline creatinine greater than 2.5 times the upper limit of normality.
• GOT/AST or GPT/ALT more than three times the upper limit of normality. Direct bilirubin greater than 1.5 times the upper limit of normality.
• Patients who are already receiving treatment with some drug for bone marrow failure may be included as long as the dose administered remains stable for at least two months. In the event that such treatment requires an increase in dose during the study, the patient must withdraw from the trial. Patients who have already started Revolade® treatment in the previous two months may also be included, and the blood counts and baseline bone marrow studies performed at the start of treatment will be used.
• Women of postpubertal age and therefore at risk of pregnancy should have a negative serum or urine pregnancy test at the screening visit and agree to use a contraceptive method throughout the treatment period and for at least one month after.