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Eltrombopag for Treatment of Fanconi Anemia

Primary Purpose

Fanconi Anemia

Status
Completed
Phase
Phase 2
Locations
Spain
Study Type
Interventional
Intervention
Eltrombopag
Sponsored by
Julian Sevilla
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Fanconi Anemia focused on measuring Fanconi Anemia

Eligibility Criteria

4 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Hospital Infantil Universitario Niño Jesús (HIUNJ)

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Eltrombopag

Arm Description

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.

Outcomes

Primary Outcome Measures

Assessing the efficacy of eltrombopag on hematopoiesis
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

Evaluation of the incidence of clonal evolution
Monitoring of cytogenetic abnormalities or specific mutations related to hematologic malignancies at months 6 and 12 from start of treatment.
Identification and tracking of adverse reactions associated with eltrombopag treatment in patients with Fanconi anemia graded
The CTCAE version 5.0 criteria will be used at 3, 6, 9 and 12 months from start of treatment.
Determination of the proportion of grafted cells
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

Full Information

First Posted
September 13, 2023
Last Updated
September 20, 2023
Sponsor
Julian Sevilla
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1. Study Identification

Unique Protocol Identification Number
NCT06045052
Brief Title
Eltrombopag for Treatment of Fanconi Anemia
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.
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
December 2, 2020 (Actual)
Primary Completion Date
June 19, 2023 (Actual)
Study Completion Date
August 29, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Julian Sevilla

4. Oversight

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

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fanconi Anemia
Keywords
Fanconi Anemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Eltrombopag
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Eltrombopag
Other Intervention Name(s)
Revolade®
Intervention Description
Eltrombopag tablets by mouth once daily for 24 weeks (6 months) with the dose depending on race, age and weight.
Primary Outcome Measure Information:
Title
Assessing the efficacy of eltrombopag on hematopoiesis
Description
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.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Evaluation of the incidence of clonal evolution
Description
Monitoring of cytogenetic abnormalities or specific mutations related to hematologic malignancies at months 6 and 12 from start of treatment.
Time Frame
6 and 12 months.
Title
Identification and tracking of adverse reactions associated with eltrombopag treatment in patients with Fanconi anemia graded
Description
The CTCAE version 5.0 criteria will be used at 3, 6, 9 and 12 months from start of treatment.
Time Frame
3, 6, 9 ans 12 months.
Title
Determination of the proportion of grafted cells
Description
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
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Julián Sevilla Navarro, MD, PhD
Organizational Affiliation
Hospital Infantil Universitario Niño Jesús (HIUNJ)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital Infantil Universitario Niño Jesús (HIUNJ)
City
Madrid
ZIP/Postal Code
28009
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
Yes

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Eltrombopag for Treatment of Fanconi Anemia

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