Eltrombopag for Fanconi Anemia

NCT03206086 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 2 other identifiers: 17012117-H-0121
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Fanconi anemia is a genetic disease. Some people with it have reduced blood cell counts. This means their bone marrow no longer works properly. These people may need blood transfusions for anemia (low red blood cells) or low platelet counts or bleeding. Researchers want to see if a new drug will help people with this disease. Objective: To find out if a new drug, eltrombopag, is effective in people with Fanconi anemia. To know how long the drug needs to be given to improve blood counts. Eligibility: People at least 6 years old with Fanconi anemia with reduced blood cell counts. Design: Participants will be screened with blood and urine tests. They will repeat this before starting to take the study drug. Participants will take eltrombopag pills by mouth once a day for 24 weeks. They will be monitored closely for side effects. Participants will have blood tests every 4 weeks while on eltrombopag. Participants will visit NIH 3 months and 6 months after starting eltrombopag. At these visits, participants will: Answer questions about their medical history, how they are feeling, and their quality of life Have a physical exam Have blood and urine tests Have a bone marrow sample taken by needle from the hip. The area will be numbed. If participants blood cell counts improve, they might join the extended access part of the study. They may continue eltrombopag for up to 3 years, with dose adjustment, taper, interruption, discontinuation, or re-initiation according to protocol criteria. After 24 weeks of treatment, if there is no improvement in blood cell counts, participants will stop taking eltrombopag. They will return for an optional follow-up visit that repeats the study visits.

Conditions

Fanconi Anemia

Keywords

DNA Repair; Inflammation; Hematopoiesis; Pancytopenia

Outcome Measures

Primary Outcomes (2)

• Proportion of Drug Responders

  Defined as one or more of the following: Peripheral Blood Response: * Platelet count increases of at least 20,000/uL above baseline or stable platelet counts with transfusion independence for those participants that were transfusion dependent prior to treatment for a minimum of 8 consecutive weeks prior to response assessment; * An increase in hemoglobin by \> 1.5g/dL or a reduction in the units of PRBC transfusions by at least 50% during the eight consecutive weeks prior to response assessment - compared with the pretreatment transfusion number in the previous 8 weeks; * At least a 100% increase in ANC in participants with a pretreatment absolute neutrophil count (ANC) of \<0.5 x 10\^9/L, or an ANC increase \>0.5 x 10\^9/L Bone Marrow Response: * \>= 2-fold increase in normal marrow CD34+ cells by CD34 immunohistochemistry or flow cytometry, and/or * \>= 2-fold increase in normal marrow cellularity as measured by standard stains (H\&E) of bone marrow biopsy/aspirate sections.

  6 months (+/- 14 day window)

• Toxicity Profile: Number of Participants With Eltrombopag-Related Adverse Events During the First 6 Months, Overall and by Event Term and Maximum CTCAE Grade

  The table reports the number of participants with at least one related adverse event overall and, for each event term, the number by maximum grade (Grade 1-2 or Grade 3 or higher). Each participant was counted once in the overall row and once per event term at the highest grade experienced; event-term categories are not mutually exclusive. Adverse events were assessed by the investigator as possibly, probably, or definitely related to eltrombopag, and were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe or medically significant), Grade 4 (life-threatening), and Grade 5 (death related to adverse event).

  Up to 6 months (+/- 14 day window)

Secondary Outcomes (6)

• Number of Participants With a Protocol-Defined Hematologic Response at Month 3

  Month 3 (+/- 14 day window)

• Number of Participants Who Relapsed During the Extension Phase

  From entry into the extension phase at Month 6 through up to 3 years of extension-phase follow-up, corresponding to up to Month 42 after initiation of eltrombopag

• Number of Participants With Clonal Evolution During Study Follow-up

  From baseline through the end of study follow-up, up to 42 months after initiation of eltrombopag

• Number of Participants With Adverse Events During the Extension Phase

  From entry into the extension phase at Month 6 through up to 3 years of extension-phase treatment and follow-up, corresponding to up to Month 42 after initiation of eltrombopag

• Change From Baseline in Health-Related Quality-of-Life Scores at Months 3 and 6

  Baseline, Month 3 (+/- 14 day window), and Month 6 (+/- 14 day window)

Study Arms (1)

Participants with Fanconi Anemia Receiving Eltrombopag

EXPERIMENTAL

Participants with Fanconi anemia will receive daily eltrombopag. Doses will be administered as follows: Non Asian populations * Ages 6 to 11: 75 mg daily; may increase up to 150 mg during the extension phase. * Ages 12 and older: 150 mg daily; may increase up to 300 mg during the extension phase. East Asian, South East Asian populations * Ages 6 to 11: 37.5 mg daily; may increase up to 150 mg during the extension phase. * Ages 12 and older: 75 mg daily; may increase up to 300 mg during the extension phase.

Drug: Eltrombopag

Interventions

Eltrombopag DRUG

Daily dose (first 6 months) * Non-Asian (6-11): 75 mg * Non-Asian (\>=12): 150 mg * East Asian, South East Asian (6-11): 37.5 mg * East Asian, South East Asian (\>=12): 75 mg

Also known as: EPAG

Participants with Fanconi Anemia Receiving Eltrombopag

Eligibility Criteria

• Age: 6 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of Fanconi anemia. Diagnosis is confirmed by a biallelic mutation in a known FANC gene and/or by positive chromosome breakage analysis in lymphocytes and/or skin fibroblasts (for mosaicism).
• One or more of the following three clinically-significant cytopenias:
• Platelet count \<= 50,000/microliter or platelet-transfusion-dependence (requiring at least 4 platelet transfusions in the 8 weeks prior to study entry)
• Neutrophil count less than 1000/microliter
• Hemoglobin less than 10 g/dL or red cell transfusion- dependence (requiring at least 4 transfusions of PRBCs (adult patient 4 units PRBC, pediatric patients at least 10ml/kg/transfusion) in the eight weeks prior to study entry.
• Failed or declined treatment with androgens (danazol or oxymetholone).
• Age \>= 6 years old.
• Weight \>=10kg.
• Transfusion Units: Single donor apheresis platelets have become the primary source of platelets in the US. Therefore, one transfused, single donor platelet apheresis product is considered 1 unit for protocol purposes. In the rare case that a patient received pooled platelet products, each completed platelet transfusion (1 bag) independent of donor units pooled, will be counted as 1 unit transfused. In analogy, each completed platelet transfusion will be counted as one unit in pediatric patients independent of the administered volume.

You may not qualify if:

• Known active or uncontrolled infections not adequately responding to appropriate therapy.
• Evidence for MDS or AML as defined by WHO criteria.
• Any cytogenetic abnormality associated with poor prognosis in FA, including gains of chromosome 3q, gains of chromosome 1q, deletions of chromosome 7, and complex cytogenetics identified from bone marrow aspirate. Patients with known biallelic mutations in BRCA2 (FANCD1).
• Active malignancy or likelihood of recurrence of malignancies within 12 months
• Moribund status such that death within 7 to 10 days is likely. Comorbidities of such severity that in the view of the investigator it would likely preclude the patient's ability to tolerate eltrombopag.
• Treatment with androgens (danazol or oxymetholone) less than 4 weeks prior to initiating eltrombopag.
• Creatinine \> 2.5 times ULN
• Direct Bilirubin \> 3.0mg/dL, indicating congenital abnormalities in the bilirubin level
• SGOT (AST) or SGPT (ALT) \>5 times the ULN normal
• Known liver cirrhosis in severity that would preclude tolerability of eltrombopag as evidenced by albumin \< 35g/L
• Known immediate or delayed hypersensitivity to EPAG or its components
• Female subjects who are nursing or pregnant (positive serum or urine Beta-human chorionic gonadotrophin (Beta-hCG pregnancy test) at screening or pre-dose on Day 1.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 30 days after the last dose of EPAG. Highly effective contraception methods include:
• Total abstinence (when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
• Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Fanconi Anemia; Inflammation; Pancytopenia

Interventions

eltrombopag

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; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cytopenia

Results Point of Contact

• Title: Andre Larochelle, M.D., Ph.D.
• Organization: National Heart, Lung, and Blood Institute (NHLBI)

larochea@nhlbi.nih.gov

301-451-7139

Study Officials

• Andre Larochelle, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2017
• First Posted: July 2, 2017
• Study Start: November 2, 2018
• Primary Completion: August 1, 2025
• Study Completion (Estimated): August 1, 2028
• Last Updated: September 16, 2026
• Results First Posted: September 16, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)