Eltrombopag With Standard Immunosuppression for Severe Aplastic Anemia

NCT01623167 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 2 other identifiers: 12015012-H-0150
• Study Type: interventional
• Target: 207
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• Severe aplastic anemia is a rare and serious blood disorder. It happens when the immune system starts to attack the bone marrow cells. This causes the bone marrow to stop making red blood cells, platelets, and white blood cells. Standard treatment for this disease is horse-ATG and cyclosporine, which suppress the immune system and stop it from attacking the bone marrow. However, this treatment does not work in all people. Some people still have poor blood cell counts even after treatment.
• Eltrombopag is a drug designed to mimic a protein in the body called thrombopoietin. It helps the body to make more platelets. It may also cause the body to make more red and white blood cells. Studies have shown that eltrombopag may be useful when added to standard treatment for severe aplastic anemia. It may help improve poor blood cell counts. Objectives: \- To test the safety and effectiveness of adding eltrombopag to standard immunosuppressive therapy for severe aplastic anemia. Eligibility: \- Individuals at least 2 years of age who have severe aplastic anemia that has not yet been treated. Design:
• Participants will be screened with a physical exam, medical history, and blood tests. Blood and urine samples will be collected.
• Participants will start treatment with horse-ATG and cyclosporine. Treatment will be given according to the standard of care for the disease.
• Cohort 1: After 14 days, participants will start taking eltrombopag. They will take eltrombopag for up to 6 months.
• Cohort 2: After 14 days, participants will start taking eltrombopag. They will take eltrombopag for up to 3 months.
• Cohort 3 and Extension Cohort: Participants will start taking eltrombopag on Day 1. They will take eltrombopag for up to 6 months.
• Participants may receive other medications to prevent infections during treatment.
• Treatment will be monitored with frequent blood tests. Participants will also fill out questionnaires about their symptoms and their quality of life.

Conditions

Severe Aplastic Anemia

Keywords

Pancytopenia; Immunosuppression; Hematopoesis; Autoimmunity; Thrombocytopenia

Outcome Measures

Primary Outcomes (1)

• Rate of Complete Hematologic Response

  Rate of complete hematologic response at six months for cohorts 1, 2 and 3.

  6 months

Secondary Outcomes (1)

• Rate of Response at 3 and 12 Months Then Yearly; Rate of Relapse; Rate of Clonal Evolution to PNH, MDS and AML; Rate of Survival; Rate of Response for Relapse Subjects That Re-start Treatment and Effects of CsA Dose Starting at Month 6 to Month 24.

  3 months to 5 years

Study Arms (4)

Cohort 1: hATG, CsA, EPAG Day 14 to Month 6

EXPERIMENTAL

Receive horse ATG days 1- 4, receive CsA day 1 to month 6, and receive eltrombopag day 14 to month 6

Drug: Cohort 1: hATG, CsA, EPAG Day 14 to Month 6

Cohort 2: hATG, CsA, EPAG Day 14 to Month 3

EXPERIMENTAL

Receive horse ATG days 1- 4, receive CsA day 1 to month 6, and receive eltrombopag day 14 to month 3

Drug: Cohort 2: hATG, CsA, EPAG Day 14 to Month 3

Cohort 3: hATG, CsA (dose reduced), EPAG day 1 to month 6

EXPERIMENTAL

Receive horse ATG days 1- 4, receive CsA day 1 to month 6 at higher dose, then reduced dose for 18months, and receive eltrombopag day 1 to month 6

Drug: Cohort 3: hATG, CsA (dose reduced), EPAG day 1 to month 6

Extrension Cohort

EXPERIMENTAL

Receive horse ATG days 1- 4, receive CsA day 1 to month 6 at higher dose, then reduced dose for 18 months, and receive eltrombopag day 1 to month 6

Drug: Extension Cohort

Interventions

Cohort 3: hATG, CsA (dose reduced), EPAG day 1 to month 6 DRUG

hATG (standard of care) administered for 4 days, CsA (standard of care) administered starting day 1 for 6 months at higher dose, then reduced dose for 18 months, eltrombopag (experimental) administered Day 1 to month 6

Also known as: Horse Antithymocyte Globulin, Cyclosporine, Promacta, Eltrombopag

Cohort 3: hATG, CsA (dose reduced), EPAG day 1 to month 6

Cohort 1: hATG, CsA, EPAG Day 14 to Month 6 DRUG

hATG (standard of care) administered for 4 days, CsA (standard of care) administered starting day 1 for 6 months, eltrombopag (experimental) administered Day 14 to month 6

Also known as: Horse Antithymocyte Globulin, Cyclosporine, Promacta, Eltrombopag

Cohort 1: hATG, CsA, EPAG Day 14 to Month 6

Cohort 2: hATG, CsA, EPAG Day 14 to Month 3 DRUG

hATG (standard of care) administered for 4 days, CsA (standard of care) administered starting day 1 for 6 months, eltrombopag (experimental) administered Day 14 to month 3

Also known as: Horse Antithymocyte Globulin, Cyclosporine, Promacta, Eltrombopag

Cohort 2: hATG, CsA, EPAG Day 14 to Month 3

Extension Cohort DRUG

Receive horse ATG days 1- 4, receive CsA day 1 to month 6 at higher dose, then reduced dose for 18 months, and receive eltrombopag day 1 to month 6

Also known as: Horse Antithymocyte Globulin (hATG), Cyclosporine (CsA), Promacta, Eltrombopag (EPAG)

Extrension Cohort

Eligibility Criteria

• Age: 2 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Severe aplastic anemia characterized by Bone marrow cellularity less than 30 percent (excluding lymphocytes)
• AND
• At least two of the following:
• Absolute neutrophil count less than 500/microL
• Platelet count less than 20,000/microL
• Absolute reticulocyte count less than 60,000/microL
• Age greater than or equal to 2 years old
• Weight greater than 12 kg

You may not qualify if:

• Known diagnosis of Fanconi anemia
• Evidence of a clonal disorder on cytogenetics performed within 12 weeks of study entry. Patients with super severe neutropenia (ANC less than 200 /microL) will not be excluded initially if cytogenetics are not available or pending. If evidence of a clonal disorder consistent with myelodysplasia is later identified, the patient will go off study.
• Prior immunosuppressive therapy with any ATG, alemtuzumab, or high dose cyclophosphamide
• SGOT or SGPT \>5 times the upper limit of normal
• Subjects with known liver cirrhosis in severity that would preclude tolerability of cyclosporine and eltrombopag as evidenced by albumin \< 35g/L
• Hypersensitivity to eltrombopag or its components
• Infection not adequately responding to appropriate therapy
• 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
• Potential subjects with cancer who are on active chemotherapeutic treatment or who take drugs with hematological effects will not be eligible
• Current pregnancy, or unwillingness to take oral contraceptives or use a barrier method of birth control or practice abstinence to refrain from pregnancy if of childbearing potential during the course of this study
• Inability to understand the investigational nature of the study or to give informed consent or does not have a legally authorized representative or surrogate that can provide informed consent.

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (12)

• 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

• Zoumbos NC, Gascon P, Djeu JY, Trost SR, Young NS. Circulating activated suppressor T lymphocytes in aplastic anemia. N Engl J Med. 1985 Jan 31;312(5):257-65. doi: 10.1056/NEJM198501313120501.

  PMID: 2981406 BACKGROUND

• Young NS, Leonard E, Platanias L. Lymphocytes and lymphokines in aplastic anemia: pathogenic role and implications for pathogenesis. Blood Cells. 1987;13(1-2):87-100.

  PMID: 3311225 BACKGROUND

• Townsley DM, Scheinberg P, Winkler T, Desmond R, Dumitriu B, Rios O, Weinstein B, Valdez J, Lotter J, Feng X, Desierto M, Leuva H, Bevans M, Wu C, Larochelle A, Calvo KR, Dunbar CE, Young NS. Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia. N Engl J Med. 2017 Apr 20;376(16):1540-1550. doi: 10.1056/NEJMoa1613878.

  PMID: 28423296 BACKGROUND

• Zaimoku Y, Patel BA, Adams SD, Shalhoub R, Groarke EM, Lee AAC, Kajigaya S, Feng X, Rios OJ, Eager H, Alemu L, Quinones Raffo D, Wu CO, Flegel WA, Young NS. HLA associations, somatic loss of HLA expression, and clinical outcomes in immune aplastic anemia. Blood. 2021 Dec 30;138(26):2799-2809. doi: 10.1182/blood.2021012895.

  PMID: 34724566 DERIVED

• Patel BA, Groarke EM, Lotter J, Shalhoub R, Gutierrez-Rodrigues F, Rios O, Quinones Raffo D, Wu CO, Young NS. Long-term outcomes in patients with severe aplastic anemia treated with immunosuppression and eltrombopag: a phase 2 study. Blood. 2022 Jan 6;139(1):34-43. doi: 10.1182/blood.2021012130.

  PMID: 34525188 DERIVED

• Zaimoku Y, Patel BA, Shalhoub R, Groarke EM, Feng X, Wu CO, Young NS. Predicting response of severe aplastic anemia to immunosuppression combined with eltrombopag. Haematologica. 2022 Jan 1;107(1):126-133. doi: 10.3324/haematol.2021.278413.

  PMID: 33910334 DERIVED

• Groarke EM, Patel BA, Gutierrez-Rodrigues F, Rios O, Lotter J, Baldoni D, St Pierre A, Shalhoub R, Wu CO, Townsley DM, Young NS. Eltrombopag added to immunosuppression for children with treatment-naive severe aplastic anaemia. Br J Haematol. 2021 Feb;192(3):605-614. doi: 10.1111/bjh.17232. Epub 2021 Jan 7.

  PMID: 33410523 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

• Giudice V, Banaszak LG, Gutierrez-Rodrigues F, Kajigaya S, Panjwani R, Ibanez MDPF, Rios O, Bleck CK, Stempinski ES, Raffo DQ, Townsley DM, Young NS. Circulating exosomal microRNAs in acquired aplastic anemia and myelodysplastic syndromes. Haematologica. 2018 Jul;103(7):1150-1159. doi: 10.3324/haematol.2017.182824. Epub 2018 Apr 19.

  PMID: 29674506 DERIVED

• Giudice V, Feng X, Lin Z, Hu W, Zhang F, Qiao W, Ibanez MDPF, Rios O, Young NS. Deep sequencing and flow cytometric characterization of expanded effector memory CD8+CD57+ T cells frequently reveals T-cell receptor Vbeta oligoclonality and CDR3 homology in acquired aplastic anemia. Haematologica. 2018 May;103(5):759-769. doi: 10.3324/haematol.2017.176701. Epub 2018 Feb 1.

  PMID: 29419434 DERIVED

• Hosokawa K, Muranski P, Feng X, Keyvanfar K, Townsley DM, Dumitriu B, Chen J, Kajigaya S, Taylor JG, Hourigan CS, Barrett AJ, Young NS. Identification of novel microRNA signatures linked to acquired aplastic anemia. Haematologica. 2015 Dec;100(12):1534-45. doi: 10.3324/haematol.2015.126128. Epub 2015 Sep 9.

  PMID: 26354756 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Anemia, Aplastic; Pancytopenia; Autoimmune Diseases; Thrombocytopenia

Interventions

Cyclosporine; eltrombopag

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Neal S. Young, M.D, NIH Principal Investigator
• Organization: National Heart Lung and Blood Institute (NHLBI)

youngns@nhlbi.nih.gov

301-496-5093

Study Officials

• Neal S 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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2012
• First Posted: June 19, 2012
• Study Start: July 2, 2012
• Primary Completion: January 30, 2018
• Study Completion (Estimated): November 30, 2029
• Last Updated: April 13, 2026
• Results First Posted: June 5, 2020

Record last verified: 2026-04

Locations

US (1)