Eltrombopag for Moderate Aplastic Anemia

NCT01328587 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 11013411-H-0134
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• Moderate aplastic anemia is a blood disease which may require frequent blood and platelet transfusions. Sometimes patients with this disease can be treated with immunosuppressive drugs. Not all patients respond and not all patients are suitable for this treatment.
• Thrombopoietin (TPO) is a protein made by the body. The bone marrow needs TPO to produce platelets. TPO may also be able to stimulate bone marrow stem cells to produce red cells and white cells. However, TPO cannot be given by mouth. This has led researchers to develop the drug eltrombopag, which acts in the same way and can be given by mouth. Eltrombopag has been shown to safely increase platelet numbers in healthy volunteers and in patients with other chronic blood diseases, including severe aplastic anemia. Researchers are interested in looking at whether eltrombopag can be given to people with moderate aplastic anemia and significantly low blood cell counts. Objectives: \- To evaluate the safety and effectiveness of eltrombopag in people with moderate aplastic anemia or patients with bone marrow failure and unilineage cytopenia who need treatment for significantly low blood cell counts. Eligibility: \- People at least 2 years of age who have moderate aplastic anemia or bone marrow failure and unilineage cytopenia,and significantly low blood cell counts. Design:
• Patients will be screened with a physical examination, medical history, blood tests, a bone marrow biopsy, and an eye exam.
• Patients will receive eltrombopag by mouth once a day.
• Patients will have weekly blood tests to monitor the effectiveness of the treatment and adjust the dose in response to possible side effects.
• Patients may continue to take eltrombopag if their platelet count or hemoglobin increases, their requirement for platelet or blood transfusion decreases after 16 to 20 weeks of treatment, and there have been no serious side effects. Access to the drug will continue until the study is closed. Patients will be asked to return for a follow-up visit 6 months after the last dose of medication.

Conditions

Moderate Aplastic Anemia; Unilineage Bone Marrow Failure Disorders

Keywords

Autoimmunity; Neutropenia; Cytokine; Hematopoiesis; Thrombocytopenia; Aplastic Anemia

Outcome Measures

Primary Outcomes (1)

• Proportion of Drug Responders

  Defined by changes in platelet count and/or platelet transfusion requirements or hemoglobin (Hb) and/or PRBC transfusion requirements and the toxicity profile as measured by CTCAE. Response for platelet lineage is defined as absolute increase of ≥20x10\^9/L above baseline at 16 or 20 weeks, with at least 2 serial measurements performed 1 week apart and sustained for 1 month or more without platelet transfusions, or for transfusion dependent patients stable platelet counts with transfusion independence for ≥ 8 weeks. Patients with anemia (untransfused hemoglobin ≤ 8.5 g/dL), a response will be an increase in Hb by ≥1.5g/dL at 4 months, with at least 2 serial measurments and sustained for 1 month or more without transfusion support OR for transfusion dependent patients, reduction of units of RCC transfused by 50%/8 weeks compared with the pretreatment transfusion number in the pretreatment transfusion number in the previous 8 weeks or transfusion independence (no transfusions ≥ 8 weeks).

  16-20 weeks from start of drug

Study Arms (1)

Eltrombopag

EXPERIMENTAL

Eltrombopag will be administered for 16 to 20 weeks at a starting dose of 50mg/day (East Asian ancestry 25mg/day). The dose will decreased and increased (maximum dose 300mg/day) based on safety and response.

Drug: Eltrombopag

Interventions

Eltrombopag DRUG

Eltrombopag will be administered for 16 to 20 weeks at a starting dose of 150mg/day (East Asian ancestry 75mg /day). The dose will decreased and increased (maximum dose 300mg/day) based on safety and response.

Eltrombopag

Eligibility Criteria

• Age: 2 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Current diagnosis of moderate aplastic anemia or unilineage bone marrow failure disorders.
• Moderate aplastic anemia is defined as aplastic anemia (hypocellular bone marrow for age) with no evidence for other disease processes causing marrow failure, and depression of at least two out of three blood counts below the normal values:
• ANC less than or equal to 1200/mm(3)
• platelet count less than or equal to 70,000/mm(3)
• anemia with hemoglobin less than or equal to 8.5 g/dL and absolute reticulocyte count less than or equal to 60,000/mm(3) in transfusion-dependent patients but not fulfilling the criteria for severe disease defined by depression of two of the three peripheral counts:
• ANC less than or equal to 500/mm(3)
• platelet count less than or equal to 20,000/mm(3)
• reticulocyte count less than or equal to 60,000/mm(3)
• Unilineage bone marrow failure disorders are defined:
• Hemoglobin less than 8.5 g/dL and reticulocyte count less than 60,000 or red cell transfusion dependent and hypocellular to normocellular bone marrow for age with significantly reduced erythroid precursors.
• OR thrombocytopenia less than or equal to 30,000/uL or platelet transfusion dependent and hypocellular to normocellular bone marrow for age with reduced megakaryocytes.
• No evidence of viral or drug suppression of the marrow, dysplasia, or underproduction anemias secondary to B12, folate, iron or other reversible causes.
• Platelet transfusion dependent is defined as the need for platelet transfusion due to platelet counts of \< 10,000/microL with no bleeding (prophylactic transfusion) or \< 20,000/microL with bleeding (therapeutic transfusion). Red cell transfusion dependent is defined as transfusion of greater than 4 units of blood in the 8 weeks prior to study entry.
• Age greater than or equal to 2 years old
• Weight greater than 12 kg

You may not qualify if:

• Known diagnosis of Fanconi anemia
• Counts that meet criteria for severe aplastic anemia
• Infection not adequately responding to appropriate therapy
• HIV positivity
• Creatinine \> 2.5 mg/dL
• Bilirubin \> 2.0 mg/dL, including congenital abnormalities in the bilirubin count
• SGOT or SGPT \>5 times the upper limit of normal
• Hypersensitivity to eltrombopag or its components
• Female subjects who are nursing or pregnant or are unwilling to take oral contraceptives or refrain from pregnancy if of childbearing potential
• Evidence of an active malignant hematological or clonal disorder, or abnormal cytogenetic studies of the bone marrow performed within 12 weeks of study entry.
• Unable to understand the investigational nature of the study or give informed consent or does not have a legally authorized representative or surrogate that can provide informed consent
• 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.
• Treatment with horse or rabbit ATG or Campath within 6 months of study entry.
• Treatment with cytokines such as G-CSF or Erythropoietin.
• Subjects with known cirrhosis in severity that would preclude tolerability of eltrombopag as evidenced by albumin less than 35g/L.

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (5)

• Young NS, Barrett AJ. The treatment of severe acquired aplastic anemia. Blood. 1995 Jun 15;85(12):3367-77. No abstract available.

  PMID: 7780125 BACKGROUND

• Young NS, Calado RT, Scheinberg P. Current concepts in the pathophysiology and treatment of aplastic anemia. Blood. 2006 Oct 15;108(8):2509-19. doi: 10.1182/blood-2006-03-010777. Epub 2006 Jun 15.

  PMID: 16778145 BACKGROUND

• Zeng W, Maciejewski JP, Chen G, Risitano AM, Kirby M, Kajigaya S, Young NS. Selective reduction of natural killer T cells in the bone marrow of aplastic anaemia. Br J Haematol. 2002 Dec;119(3):803-9. doi: 10.1046/j.1365-2141.2002.03875.x.

  PMID: 12437663 BACKGROUND

• Fan X, Desmond R, Winkler T, Young DJ, Dumitriu B, Townsley DM, Gutierrez-Rodrigues F, Lotter J, Valdez J, Sellers SE, Barranta ME, Shalhoub RN, Wu CO, Albitar M, Calvo KR, Young NS, Dunbar CE. Eltrombopag for patients with moderate aplastic anemia or uni-lineage cytopenias. Blood Adv. 2020 Apr 28;4(8):1700-1710. doi: 10.1182/bloodadvances.2020001657.

  PMID: 32330244 DERIVED

• Giudice V, Wu Z, Kajigaya S, Fernandez Ibanez MDP, Rios O, Cheung F, Ito S, Young NS. Circulating S100A8 and S100A9 protein levels in plasma of patients with acquired aplastic anemia and myelodysplastic syndromes. Cytokine. 2019 Jan;113:462-465. doi: 10.1016/j.cyto.2018.06.025. Epub 2018 Jun 27.

  PMID: 29958797 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Autoimmune Diseases; Neutropenia; Thrombocytopenia; Anemia, Aplastic

Interventions

eltrombopag

Condition Hierarchy (Ancestors)

Immune System Diseases; Agranulocytosis; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders; Blood Platelet Disorders; Anemia; Bone Marrow Failure Disorders; Bone Marrow Diseases

Results Point of Contact

• Title: Dr David Young
• Organization: National Heart Lung and Blood Institute

david.young2@nih.gov

301.827.7823

Study Officials

• Cynthia E Dunbar, 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: April 1, 2011
• First Posted: April 4, 2011
• Study Start: March 13, 2012
• Primary Completion: March 30, 2018
• Study Completion: January 6, 2026
• Last Updated: April 23, 2026
• Results First Posted: April 23, 2019

Record last verified: 2026-04

Locations

US (1)