Severe Aplastic AnemiaPhase 1/2NCT01623167
Eltrombopag With Standard Immunosuppression for Severe Aplastic Anemia
A Phase 1/2 study testing Cohort 1: hATG, CsA, EPAG Day 14 to Month 6, Cohort 2: hATG, CsA, EPAG Day 14 to Month 3 and Cohort 3: hATG, CsA (dose reduced), EPAG day 1 to month 6 in people with Severe Aplastic Anemia, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 95 years
- Conditions the study is for
- Severe Aplastic Anemia
- What is being tested?
- Cohort 1: hATG, CsA, EPAG Day 14 to Month 6, Cohort 2: hATG, CsA, EPAG Day 14 to Month 3 and Cohort 3: hATG, CsA (dose reduced), EPAG day 1 to month 6
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 207 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Jul 2012to 30 Nov 2029
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 95 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Eltrombopag Added to Standard Immunosuppression in Treatment-Naive Severe Aplastic Anemia
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.
Read more
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.
Read the detailed description
Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disorder characterized by pancytopenia and a hypocellular bone marrow. Allogeneic bone marrow transplantation offers the opportunity for cure in younger patients, but most are not suitable candidates for transplantation due to advanced age or lack of a histocompatible donor. Comparable long-term survival in SAA is attainable with immunosuppressive treatment with horse anti-thymocyte globulin (h-ATG) and cyclosporine (CsA). However, of those patients treated with h-ATG/CsA, one quarter to one third will not respond, and 30-40% of responders relapse. The majority of the hematologic responses observed following initial h-ATG/CsA are partial, with only a few patients achieving normal blood counts. Furthermore, analysis of our own extensive clinical data suggests that poor blood count responses to a single course of ATG (non-robust responders), even when transfusion-independence is achieved, predicts a worse prognosis than when robust hematologic improvement is achieved (protocol 90-H-0146). The explanation for partial recovery and relapse are not fully understood, but incomplete elimination of auto-reactive T cells and insufficient stem cell reserve are both possible. Furthermore, 10-15% of SAA patients treated with standard immunosuppression will develop an abnormal karyotype in follow-up, with monosomy 7 being most common, which portends progression to myelodysplasia and leukemia. In contrast, malignant clonal evolution is rare in complete responders to immunosuppression. Although horse ATG/CsA represented a major advance in the treatment of SAA, refractoriness, incomplete responses, relapse, and clonal evolution limit the success of this modality. Thus, newer regimens are needed to address these limitations, and provide a better alternative to stem cell transplantation.
One approach to augment the quality of hematologic responses is to improve underlying stem cell function. Previous attempts to improve responses in SAA with hematopoietic cytokines including erythropoietin, G-CSF, and stem cell factor, have failed. Thrombopoietin (TPO) is the principal endogenous regulator of platelet production. In addition, TPO also has stimulatory effects on more primitive multilineage progenitors and stem cells in vitro and in animal models. Eltrombopag (Promacta ), an oral 2nd generation small molecule TPO-agonist, is currently approved for treatment of chronic immune thrombocytopenic purpura (ITP), chronic hepatitis C-associated thrombocytopenia, and severe aplastic anemia who have had an insufficient response to immunosuppressive therapy. Eltrombopag increases platelets in healthy subjects and in thrombocytopenic patients with chronic ITP and hepatitis C virus (HCV) infection. Our Branch recently completed a pilot study of eltrombopag in refractory SAA. We saw encouraging clinical results in a cohort of patients who have failed on average two prior immunosuppressive regimens (Olnes et al. ASH Annual Meeting Abstracts, San Diego, CA, 2011, oral presentation and N Engl J Med 2012;367:11-9.1). Of the twenty-five SAA patients treated with eltrombopag by mouth for three months, eleven (44%) patients met protocol criteria of clinically meaningful hematologic responses, without significant toxicity. Nine patients demonstrated an improvement in thrombocytopenia (>20k/ L increase or transfusion independence), hemoglobin improved in two patients (>1.5g/dL or achieved transfusion independence, and four patients had a significant response in their neutrophil count. When responders continued the drug beyond three months, the hematologic response to eltrombopag increased; a trilineage response was observed in four patients, and a bilineage response occurred in another four, with median follow-up of 13 months. These results suggest that stem cell depletion, a major component of the pathophysiology of SAA, might be directly addressed by eltrombopag administration. The aim of the current study would be to improve the hematologic response rate and its quality, as well as prevent late complications such as relapse and clonal progression, by addition of eltrombopag to standard immunosuppressive therapy.
This trial will evaluate the safety and efficacy of combining eltrombopag with standard hATG/CSA as first line therapy in patients with SAA. The primary endpoint will be the rate of complete hematologic response at six months. Secondary endpoints are relapse, robust hematologic blood count recovery at 3, 6, and 12 months, survival, clonal evolution to myelodysplasia and leukemia, marrow stem cell content and hematological response of relapse patients that re-start treatment.
- Conditions
- Severe Aplastic Anemia
- Being tested
- Cohort 1: hATG, CsA, EPAG Day 14 to Month 6, Cohort 2: hATG, CsA, EPAG Day 14 to Month 3, Cohort 3: hATG, CsA (dose reduced), EPAG day 1 to month 6, Extension Cohort
- Keywords
- Pancytopenia, Immunosuppression, Hematopoesis, Autoimmunity, Thrombocytopenia
- Medical subject headings
- Anemia, Aplastic, Pancytopenia, Autoimmune Diseases, Thrombocytopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cohort 1: hATG, CsA, EPAG Day 14 to Month 6Drug
Also called Horse Antithymocyte Globulin, Cyclosporine, Promacta, Eltrombopag
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
Cohort 2: hATG, CsA, EPAG Day 14 to Month 3Drug
Also called Horse Antithymocyte Globulin, Cyclosporine, Promacta, Eltrombopag
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
Cohort 3: hATG, CsA (dose reduced), EPAG day 1 to month 6Drug
Also called Horse Antithymocyte Globulin, Cyclosporine, Promacta, Eltrombopag
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
Extension CohortDrug
Also called Horse Antithymocyte Globulin (hATG), Cyclosporine (CsA), Promacta, Eltrombopag (EPAG)
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: 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 Receives: Drug: Extension Cohort |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Complete Hematologic Response
Rate of complete hematologic response at six months for cohorts 1, 2 and 3.
Measured: 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.
Secondary endpoints will also be evaluated for the study to include: (a) hematological response at 3 and 12 months and yearly thereafter; (b) relapse (c) clonal evolution to PNH, clonal chromosomal population in bone marrow, myelodysplasia by morphology, or acute leukemia; (d) survival; (e) health-related quality of life; (f) hematological response of relapse subjects that re-start treatment; and (g) affects of a 2.0mg/kg/day CsA dose starting month 6 for 18 months until month 24 on the rate of relapse of subjects deemed responders at month 6.
Measured: 3 months to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2012 (estimated)
- Study start2 Jul 2012
- Primary completion30 Jan 2018
- Study completion30 Nov 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Severe Aplastic AnemiaStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 207 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Neal S Young, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01623167
- Sponsor's protocol ID
- 120150
- Other IDs
- 12-H-0150
- Status last verified
- Apr 2026
- First submitted
- 14 Jun 2012
- Last updated
- 13 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 16778145Zoumbos 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.
PubMed 2981406Young 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.
PubMed 3311225Townsley 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.
PubMed 28423296Zaimoku 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.
PubMed 34724566Patel 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.
PubMed 34525188Zaimoku 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.
PubMed 33910334Groarke 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.
PubMed 33410523Giudice 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.
PubMed 29958797Giudice 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.
PubMed 29674506Giudice 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.
PubMed 29419434Hosokawa 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.
PubMed 26354756
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Eltrombopag Added to Standard Immunosuppression in Treatment-Naive Severe Aplastic Anemia
- ClinicalTrials.gov ID
- NCT01623167
- Acronym / sponsor ID
- 120150
- Conditions
- Severe Aplastic Anemia
- Keywords
- Pancytopenia, Immunosuppression, Hematopoesis, Autoimmunity, Thrombocytopenia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 207 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Collaborators
- Novartis
- Study start
- 2 Jul 2012 (actual)
- Primary completion
- 30 Jan 2018 (actual)
- Study completion
- 30 Nov 2029 (estimated)
- First posted
- 19 Jun 2012 (estimated)
- Results
- Posted 5 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disorder characterized by pancytopenia and a hypocellular bone marrow. Allogeneic bone marrow transplantation offers the opportunity for cure in younger patients, but most are not suitable candidates for transplantation due to advanced age or lack of a histocompatible donor. Comparable long-term survival in SAA is attainable with immunosuppressive treatment with horse anti-thymocyte globulin (h-ATG) and cyclosporine (CsA). However, of those patients treated with h-ATG/CsA, one quarter to one third will not respond, and 30-40% of responders relapse. The majority of the hematologic responses observed following initial h-ATG/CsA are partial, with only a few patients achieving normal blood counts. Furthermore, analysis of our own extensive clinical data suggests that poor blood count responses to a single course of ATG (non-robust responders), even when transfusion-independence is achieved, predicts a worse prognosis than when robust hematologic improvement is achieved (protocol 90-H-0146). The explanation for partial recovery and relapse are not fully understood, but incomplete elimination of auto-reactive T cells and insufficient stem cell reserve are both possible. Furthermore, 10-15% of SAA patients treated with standard immunosuppression will develop an abnormal karyotype in follow-up, with monosomy 7 being most common, which portends progression to myelodysplasia and leukemia. In contrast, malignant clonal evolution is rare in complete responders to immunosuppression. Although horse ATG/CsA represented a major advance in the treatment of SAA, refractoriness, incomplete responses, relapse, and clonal evolution limit the success of this modality. Thus, newer regimens are needed to address these limitations, and provide a better alternative to stem cell transplantation.
One approach to augment the quality of hematologic responses is to improve underlying stem cell function. Previous attempts to improve responses in SAA with hematopoietic cytokines including erythropoietin, G-CSF, and stem cell factor, have failed. Thrombopoietin (TPO) is the principal endogenous regulator of platelet production. In addition, TPO also has stimulatory effects on more primitive multilineage progenitors and stem cells in vitro and in animal models. Eltrombopag (Promacta ), an oral 2nd generation small molecule TPO-agonist, is currently approved for treatment of chronic immune thrombocytopenic purpura (ITP), chronic hepatitis C-associated thrombocytopenia, and severe aplastic anemia who have had an insufficient response to immunosuppressive therapy. Eltrombopag increases platelets in healthy subjects and in thrombocytopenic patients with chronic ITP and hepatitis C virus (HCV) infection. Our Branch recently completed a pilot study of eltrombopag in refractory SAA. We saw encouraging clinical results in a cohort of patients who have failed on average two prior immunosuppressive regimens (Olnes et al. ASH Annual Meeting Abstracts, San Diego, CA, 2011, oral presentation and N Engl J Med 2012;367:11-9.1). Of the twenty-five SAA patients treated with eltrombopag by mouth for three months, eleven (44%) patients met protocol criteria of clinically meaningful hematologic responses, without significant toxicity. Nine patients demonstrated an improvement in thrombocytopenia (>20k/ L increase or transfusion independence), hemoglobin improved in two patients (>1.5g/dL or achieved transfusion independence, and four patients had a significant response in their neutrophil count. When responders continued the drug beyond three months, the hematologic response to eltrombopag increased; a trilineage response was observed in four patients, and a bilineage response occurred in another four, with median follow-up of 13 months. These results suggest that stem cell depletion, a major component of the pathophysiology of SAA, might be directly addressed by eltrombopag administration. The aim of the current study would be to improve the hematologic response rate and its quality, as well as prevent late complications such as relapse and clonal progression, by addition of eltrombopag to standard immunosuppressive therapy.
This trial will evaluate the safety and efficacy of combining eltrombopag with standard hATG/CSA as first line therapy in patients with SAA. The primary endpoint will be the rate of complete hematologic response at six months. Secondary endpoints are relapse, robust hematologic blood count recovery at 3, 6, and 12 months, survival, clonal evolution to myelodysplasia and leukemia, marrow stem cell content and hematological response of relapse patients that re-start treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: hATG, CsA, EPAG Day 14 to Month 6 | Experimental | Drug: Cohort 1: hATG, CsA, EPAG Day 14 to Month 6Receive horse ATG days 1- 4, receive CsA day 1 to month 6, and receive eltrombopag day 14 to month 6 |
| Cohort 2: hATG, CsA, EPAG Day 14 to Month 3 | Experimental | Drug: Cohort 2: hATG, CsA, EPAG Day 14 to Month 3Receive horse ATG days 1- 4, receive CsA day 1 to month 6, and receive eltrombopag day 14 to month 3 |
| Cohort 3: hATG, CsA (dose reduced), EPAG day 1 to month 6 | Experimental | Drug: Cohort 3: hATG, CsA (dose reduced), EPAG day 1 to month 6Receive 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 |
| Extrension Cohort | Experimental | Drug: Extension CohortReceive 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 |
Who may qualify
- Ages
- 2 to 95 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cohort 1: hATG, CsA, EPAG Day 14 to Month 6Also: Horse Antithymocyte Globulin, Cyclosporine, Promacta, EltrombopaghATG (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 | Drug | Cohort 1: hATG, CsA, EPAG Day 14 to Month 6 |
| Cohort 2: hATG, CsA, EPAG Day 14 to Month 3Also: Horse Antithymocyte Globulin, Cyclosporine, Promacta, EltrombopaghATG (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 | Drug | Cohort 2: hATG, CsA, EPAG Day 14 to Month 3 |
| Cohort 3: hATG, CsA (dose reduced), EPAG day 1 to month 6Also: Horse Antithymocyte Globulin, Cyclosporine, Promacta, EltrombopaghATG (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 | Drug | Cohort 3: hATG, CsA (dose reduced), EPAG day 1 to month 6 |
| Extension CohortAlso: Horse Antithymocyte Globulin (hATG), Cyclosporine (CsA), Promacta, Eltrombopag (EPAG)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 | Extrension Cohort |
Primary outcome
Rate of Complete Hematologic Response
Time frame: 6 months
Rate of complete hematologic response at six months for cohorts 1, 2 and 3.
1 secondary outcome
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.
Time frame: 3 months to 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 16778145Young 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.
- Background: PubMed 2981406Zoumbos 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.
- Background: PubMed 3311225Young 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.
- Background: PubMed 28423296Townsley 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.
- Derived from this study: PubMed 34724566Zaimoku 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.
- Derived from this study: PubMed 34525188Patel 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.
- Derived from this study: PubMed 33910334Zaimoku 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.
- Derived from this study: PubMed 33410523Groarke 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.
- Derived from this study: PubMed 29958797Giudice 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.
- Derived from this study: PubMed 29674506Giudice 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.
- Derived from this study: PubMed 29419434Giudice 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.
- Derived from this study: PubMed 26354756Hosokawa 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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Neal S Young, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Cohort 1: hATG, CsA, EPAG Day 14 to Month 6, Cohort 2: hATG, CsA, EPAG Day 14 to Month 3 and Cohort 3: hATG, CsA (dose reduced), EPAG day 1 to month 6 in people with Severe Aplastic Anemia, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 13 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of Complete Hematologic Response (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01623167, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2026.