Treatment of Refractory Diamond-Blackfan Anemia With Eltrombopag

NCT04269889 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 20002120-H-0021
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Diamond-Blackfan anemia (DBA) is treated with steroids. But some people cannot take steroids, or steroids don t work. Other patients must get blood transfusions regularly which are time consuming and can have significant side effects. The drug eltrombopag can increase red blood cells. Researchers want to see if it can help people with DBA and, if so, for how long. Objective: To study the safety and efficacy of eltrombopag in people with DBA who have not responded to steroids or could not take them. Eligibility: People ages 2 and older with DBA who did not respond to steroids or could not take them, or their disease has returned despite taking them Design: Participants will be screened with: Medical and medicine history Physical exam MRI: Participants will lie in a machine that takes pictures of the liver. Blood and urine tests Bone marrow biopsy: A thin needle will remove a marrow sample from the participant's hip bone. Electrocardiogram Participants will take eltrombopag pills once daily for 24 weeks. They will have blood taken every 2 weeks. Participants will have visits 6 months. At 6 months, they will repeat all the screening tests and also have: Quality-of-life questionnaire Neurodevelopmental test (for participants younger than 18 years) If participants blood cell counts improve, they may keep taking eltrombopag for up to 3 more years. If so, they will have blood taken every 4 weeks. They will visit NIH every 6 months and repeat the above tests. Participants will be monitored for up to 3 years after they stop taking eltrombopag. They will visit NIH 6 months after treatment ends. If participants blood counts go down after treatment ends, they may restart the drug....

Conditions

Anemia, Diamond-Blackfan

Keywords

Chelation, Ribosomopathy; Erythroid Aplasia; Iron Homeostasis; Hemoglobin Synthesis; Heme Synthesis

Outcome Measures

Primary Outcomes (3)

• Participants That Responded to Eltrombopag

  Participants that responded to Eltrombopag as defined by: Response to treatment will be defined by one or more of the following: * Erythroid response for subjects with a pretreatment hemoglobin less than 9 G/dL will be defined as an increase in hemoglobin by \>1.5 G/dL from enrollment baseline, and/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.

  6 months (24 weeks +/- 14 days)

• Time (Weeks) to Response

  Time-to-response in weeks will also be measured according to the time from Eltrombopag initiation to the first time the patient met criteria for response. Response to treatment will be defined by one or more of the following: * Erythroid response for subjects with a pretreatment hemoglobin less than 9 G/dL will be defined as an increase in hemoglobin by \>1.5 G/dL from enrollment baseline, and/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.

  6 months (24 weeks +/- 14 days)

• Number of Adverse Events

  Number of Adverse Events Toxicity profile as measured by using the Common Terminology Criteria for Adverse Events (CTCAE version 5.0) for grade 2 and above. According to https://ctep.cancer.gov/, CTCAE is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. CTCAE grades are defined as: Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age appropriate instrumental activities of daily living. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 Life-threatening consequences; urgent intervention indicated.

  6 months (24 weeks +/- 14 days)

Secondary Outcomes (9)

• Number of Participants That Responded to Eltrombopag

  3 Months

• Number of Participants With Robust Response to Eltrombopag

  3 Months, 6 Months, Up to 27 Months

• Median Change in Platelet Count

  Baseline, 3 months

• Median Change Absolute Neutrophil Count

  Baseline, Month 3

• Number of Participants That Experienced Relapse

  6 months up to 27 months

Study Arms (1)

Refractory Diamond-Blackfan Anemia in Eltrombopag

EXPERIMENTAL

Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily. To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.

Drug: Eltrombopag

Interventions

Eltrombopag DRUG

Eltrombopag will be administered to participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily. To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.

Also known as: EPAG

Refractory Diamond-Blackfan Anemia in Eltrombopag

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be participate in this study, individuals must meet all of the following criteria:
• Diamond-Blackfan anemia defined as anemia presenting on or before the third year of life with reticulocytopenia and greatly reduced or absent bone marrow erythroid precursors, supported by, but not requiring either:
• familial history
• gene mutation testing demonstrating a known disease-causing mutation or a mutation of disease-associated gene in combination with clinical characteristics of DBA
• Patients with late-onset DBA (diagnosed after the third year of life) may also be included if gene mutation testing confirms a disease -causing mutation as above.
• Clinically-significant anemia as defined as either:
• hemoglobin less than 9.0 g/dL
• red cell transfusion of at least 2 units PRBC for adults or 30 cc/kg for children (whichever is less) in the eight weeks prior to study enrollment
• Relapsed and/or steroid-refractory or intolerant of systemic corticosteroids
• Age greater than or equal to 2 years
• Weight greater than or equal to 12 kilograms
• Residence within the United States of America or territories, or able to reside within the US or its territories while on drug during trial participation

You may not qualify if:

• Platelet count \> 400,000 / microliter
• Stage 4 or greater kidney disease as defined by creatinine \> 2.5 mg/ dL or GFR \< 30 mL/min/1.73 m(2)
• For pediatric patients 17-years-old or younger, GFR shall be used. This can be estimated using the bedside Schwartz equation, the Counahan-Barratt method, or a similar methodology. Direct measurement including, but not limited to, 24-hour urine creatinine clearance or radiographic methods is recommended for patients with stage 3 disease (GFR less than or equal to 45 mL/min/1.73 m(2)).
• Direct bilirubin \> 2.0 mg/ dL, including congenital abnormalities in the bilirubin level
• SGOT (AST) or SGPT (ALT) \> 5 times the upper limit of normal
• Treatment with androgens (danazol or oxymetholone) or corticosteroids less than 4 weeks prior to initiating eltrombopag.
• Physiologic steroid replacement for adrenal insufficiency or other similar conditions is not exclusive of trial participation
• Treatment with any medications that may interfere with the metabolism of eltrombopag (e.g., CYP1A2 and CYP2C8 modulators) or whose own altered metabolism by eltrombopag cannot be adjusted for
• Hypersensitivity to eltrombopag or its components
• Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary, infectious, or metabolic disease of such severity that it would preclude the patient s ability to tolerate protocol therapy, or that death within 7-10 days is likely
• Life expectancy of less than 3 months for any cause
• Subjects with known liver cirrhosis in severity that would preclude tolerability of eltrombopag as evidenced by albumin \< 3.5g/dL
• History or current diagnosis of cardiac disease indicating significant risk of safety for patients participating in the study such as uncontrolled or significant cardiac disease, including any of the following:
• Recent myocardial infarction (within last 6 months),
• Uncontrolled congestive heart failure,

Sponsors & Collaborators

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

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

Anemia, Diamond-Blackfan; Anemia, Aplastic

Interventions

eltrombopag

Condition Hierarchy (Ancestors)

Anemia, Hypoplastic, Congenital; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Red-Cell Aplasia, Pure; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Bone Marrow Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: David J. Young, MD, PhD
• Organization: National Heart, Lung, and Blood Institute (NHLBI) at the National Institutes of Health (NIH)

david.young2@nih.gov

301.827.7823

Study Officials

• David J Young, 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 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2020
• First Posted: February 17, 2020
• Study Start: December 1, 2020
• Primary Completion: August 16, 2022
• Study Completion: February 16, 2024
• Last Updated: April 27, 2025
• Results First Posted: September 13, 2023

Record last verified: 2024-11

Locations

US (1)