Extended Dosing With Eltrombopag for Severe Aplastic Anemia

NCT01891994 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: 13013313-H-0133NCT01891994
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Eltrombopag is a drug being tested for treating severe aplastic anemia. It can help improve blood counts in these patients. However, researchers do not know how long the drug can and should be taken for this type of anemia. Objectives: \- To look at whether 6 months of treatment with eltrombopag can improve patient s blood counts. Eligibility: \- Individuals at least 2 years of age who are taking eltrombopag for severe aplastic anemia. Design:

• Participants will take eltrombopag by mouth once a day for 6 months.
• Blood samples will be collected every 2 weeks for the first 6 months. Bone marrow samples will be collected at 3 and 6 months. These samples will look at the effects of the study drug on the marrow.
• Participants will continue to take the study drug for as long as it is effective and if the side effects are not severe.

Conditions

Severe Aplastic Anemia (SAA)

Keywords

Cytokine; Hematopoiesis; Autoimmunity; Thrombocytopenia; Neutropenia

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Drug Response as Defined by Clinically-signficant Hematologic Improvements

  Defined as unilineage or multilineage recovery by 1 or more of the following: 1) platelet response (increase to 20 × 103/μL above baseline or stable platelet counts with transfusion independence for a minimum of 8 weeks in those who were transfusion dependent on entry into the protocol); (2) erythroid response (when pretreatment hemoglobin was \<9 g/dL, defined as an increase in hemoglobin by 1.5 g/dL or, in transfused patients, a reduction in the units of packed red blood cell transfusions by an absolute number of at least 4 transfusions for 8 consecutive weeks, compared with the pretreatment transfusion number in the previous 8 weeks); and (3) neutrophil response (when pretreatment absolute neutrophil count \[ANC\] of \<0.5 × 103/μL as at least a 100% increase in ANC, or an ANC increase \>0.5 × 103/μL, and the toxicity profile as measured using Common Terminology Criteria for Adverse Events).

  24 weeks

Study Arms (1)

Eltrombopag

EXPERIMENTAL

Administration of eltrombopag at a dose of 150mg/day for 6 months

Drug: Eltrombopag

Interventions

Eltrombopag DRUG

Oral administration of eltrombopag 150mg/day (75 mg/day for East Asian ancestry) for 6 months

Also known as: Promacta

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:

• Previous diagnosis of refractory severe aplastic anemia and following at least one treatment course of immunosuppression with a regimen containing antithymocyte globulin, alemtuzumab or cyclophosphamide.
• One or more of the following three clinically-significant cytopenias: platelet count less than or equal to 30,000/micro L or platelet-transfusion-dependence (requiring at least 4 platelet transfusions in the 8 weeks prior to study entry); neutrophil count less than 500/micro L; hemoglobin less than 9.0 g/dL or red cell transfusion-dependence (requiring at least 4 units of PRBCs in the eight weeks prior to study entry)
• Age greater than or equal to 2 years old
• Weight \> 12 kg

You may not qualify if:

• Infection not adequately responding to appropriate therapy
• Evidence of a clonal disorder on cytogenetics performed within 12 weeks of study entry.
• Creatinine \> 2.5 mg/dL
• Direct Bilirubin \> 2.0 mg/dL
• SGOT or SGPT \>5 times the upper limit of normal
• Hypersensitivity to eltrombopag or its components\<TAB\>
• Female subjects who are nursing or pregnant or are unwilling to take oral contraceptives or refrain from pregnancy if of childbearing potential
• Unable to understand the investigational nature of the study or give 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 ATG, cyclophophamide or alemtuzamab within 6 months of study entry.

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 (2)

• Zhao Z, Sun Q, Sokoll LJ, Streiff M, Cheng Z, Grasmeder S, Townsley DM, Young NS, Dunbar CE, Winkler T. Eltrombopag mobilizes iron in patients with aplastic anemia. Blood. 2018 May 24;131(21):2399-2402. doi: 10.1182/blood-2018-01-826784. Epub 2018 Apr 9. No abstract available.

  PMID: 29632023 BACKGROUND

• Winkler T, Fan X, Cooper J, Desmond R, Young DJ, Townsley DM, Scheinberg P, Grasmeder S, Larochelle A, Desierto M, Valdez J, Lotter J, Wu C, Shalhoub RN, Calvo KR, Young NS, Dunbar CE. Treatment optimization and genomic outcomes in refractory severe aplastic anemia treated with eltrombopag. Blood. 2019 Jun 13;133(24):2575-2585. doi: 10.1182/blood.2019000478. Epub 2019 Apr 16.

  PMID: 30992268 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Anemia, Aplastic; Autoimmune Diseases; Thrombocytopenia; Neutropenia

Interventions

eltrombopag

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dunbar, Cynthia
• Organization: National Heart Lung and Blood Institute

dunbarc@nhlbi.nih.gov

+1 301 827 1164

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: June 28, 2013
• First Posted: July 3, 2013
• Study Start: June 28, 2013
• Primary Completion: October 16, 2017
• Study Completion: August 24, 2022
• Last Updated: April 25, 2023
• Results First Posted: December 4, 2018

Record last verified: 2023-03

Locations

US (1)