Eltrombopag for Treatment of Fanconi Anemia

• ClinicalTrials.gov Identifier: NCT06045052
• Recruitment Status: Completed
• First Posted: September 21, 2023
• Last Update Posted: September 21, 2023
• Sponsor: Julian Sevilla
• Information provided by (Responsible Party): Julian Sevilla, Hospital Infantil Universitario Niño Jesús, Madrid, Spain

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Fanconi Anemia	Drug: Eltrombopag	Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Phase II Study to Assess the Efficacy and Safety of Eltrombopag for the Treatment of Children and Adolescents With Fanconi Anemia.
• Actual Study Start Date: December 2, 2020
• Actual Primary Completion Date: June 19, 2023
• Actual Study Completion Date: August 29, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Eltrombopag; Eltrombopag will be administered orally once daily for 24 weeks (6 months) and the dose will be adjusted according to race, age and weight. Patients who achieve at least partial remission may continue treatment for up to one year.	Drug: Eltrombopag; Eltrombopag tablets by mouth once daily for 24 weeks (6 months) with the dose depending on race, age and weight.; Other Name: Revolade®

Outcome Measures

Primary Outcome Measures :

1. Assessing the efficacy of eltrombopag on hematopoiesis [ Time Frame: 6 months ]
   An analysis of the proportion of patients with complete response and/or partial response after 6 months of treatment in the absence of transfusions or rescue therapy will be performed.

Secondary Outcome Measures :

1. Evaluation of the incidence of clonal evolution [ Time Frame: 6 and 12 months. ]
   Monitoring of cytogenetic abnormalities or specific mutations related to hematologic malignancies at months 6 and 12 from start of treatment.
2. Identification and tracking of adverse reactions associated with eltrombopag treatment in patients with Fanconi anemia graded [ Time Frame: 3, 6, 9 ans 12 months. ]
   The CTCAE version 5.0 criteria will be used at 3, 6, 9 and 12 months from start of treatment.
3. Determination of the proportion of grafted cells [ Time Frame: 12 months ]
   It will be evaluated in patients seen to have reverted cells, involving either correction of a pathogenic mutation (natural mosaicism) or due to the infusion of hematopoietic stem cells transduced with the lentiviral vector carrying the FANCA gene

Eligibility Criteria

• Ages Eligible for Study: 4 Years to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Spain

Hospital Infantil Universitario Niño Jesús (HIUNJ)

Madrid, Spain, 28009

Sponsors and Collaborators

Julian Sevilla

Investigators

• Principal Investigator: Julián Sevilla Navarro, MD, PhD; Hospital Infantil Universitario Niño Jesús (HIUNJ)

More Information

• Responsible Party: Julian Sevilla, Dr. Julián Sevilla Navarro, MD, PhD, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
• ClinicalTrials.gov Identifier: NCT06045052
• Other Study ID Numbers: FANCREV
• First Posted: September 21, 2023
• Last Update Posted: September 21, 2023
• Last Verified: September 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

• 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

Keywords provided by Julian Sevilla, Hospital Infantil Universitario Niño Jesús, Madrid, Spain:

Fanconi Anemia

Additional relevant MeSH terms:

Fanconi Syndrome; Anemia; Fanconi Anemia; Hematologic Diseases; Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Bone Marrow Diseases; Genetic Diseases, Inborn; DNA Repair-Deficiency Disorders; Metabolic Diseases; Renal Tubular Transport, Inborn Errors; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases