A Phase 1/2 interventional study of Cohort 1: hATG, CsA, EPAG Day 14 to Month 6 and Cohort 2: hATG, CsA, EPAG Day 14 to Month 3 in Severe Aplastic Anemia, sponsored by National Heart, Lung, and Blood Institute (NHLBI). Active, not recruiting at 1 site in United States. Open to participants aged 2 Years to 95 Years. Per ClinicalTrials.gov, last updated 2026-04-13.
Sponsored by National Heart, Lung, and Blood Institute (NHLBI) · Phase 1/2, Interventional, and Treatment
Background:
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:
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.
371 studies on the registry are indexed under Anemia, Aplastic; 98 are open to participants now.
This study's enrollment of 207 is above the median of 37 across 281 interventional studies indexed under Anemia, Aplastic.
Browse Anemia, Aplastic studies →National Heart, Lung, and Blood Institute (NHLBI) is the lead sponsor of 1,143 studies on the registry; 71 are open to participants now.
Of its 58 completed or terminated interventional studies of FDA-regulated products, 51 (88%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Severe aplastic anemia characterized by Bone marrow cellularity less than 30 percent (excluding lymphocytes)
AND
At least two of the following:
Absolute reticulocyte count less than 60,000/microL
EXCLUSION CRITERIA:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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
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
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
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
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
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
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)
Rate of Complete Hematologic Response
Rate of complete hematologic response at six months for cohorts 1, 2 and 3.
Time frame: 6 months
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.
Time frame: 3 months to 5 years
| Milestone | hATG, CsA, EPAG Day 14 to Month 6 | hATG, CsA, EPAG Day 14 to Month 3 | hATG, CsA (Dose Reduced), EPAG Day 1 to Month 6 |
|---|---|---|---|
| Started | 30 | 31 | 31 |
| Completed | 13 | 17 | 18 |
| Not completed | 17 | 14 | 13 |
Rate of complete hematologic response at six months for cohorts 1, 2 and 3.
| Participants | hATG, CsA, EPAG Day 14 to Month 6 | hATG, CsA, EPAG Day 14 to Month 3 | hATG, CsA (Dose Reduced), EPAG Day 1 to Month 6 |
|---|---|---|---|
| No Response | 3 | 2 | 1 |
| Partial Response | 14 | 19 | 11 |
| Complete Response | 10 | 8 | 18 |
| Off study/Not Evaluable | 3 | 2 | 1 |
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.
Results for this outcome have not been posted.
Collected over 6 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| hATG, CsA, EPAG Day 14 to Month 6 | 1/30 (3.3%) | 17/30 (56.7%) | 30/30 (100%) |
| hATG, CsA, EPAG Day 14 to Month 3 | 0/31 (0%) | 15/31 (48.4%) | 31/31 (100%) |
| hATG, CsA (Dose Reduced), EPAG Day 1 to Month 6 | 0/31 (0%) | 14/31 (45.2%) | 31/31 (100%) |
| Event | hATG, CsA, EPAG Day 14 to Month 6 | hATG, CsA, EPAG Day 14 to Month 3 | hATG, CsA (Dose Reduced), EPAG Day 1 to Month 6 |
|---|---|---|---|
| Febrile neutropeniaBlood and lymphatic system disorders | 4/30 | 5/31 | 1/31 |
| Serum sicknessImmune system disorders | 0/30 | 2/31 | 4/31 |
| AppendicitisGastrointestinal disorders | 2/30 | 0/31 | 0/31 |
| HeadacheNervous system disorders | 2/30 | 1/31 | 0/31 |
| AnemiaBlood and lymphatic system disorders | 0/30 | 2/31 | 0/31 |
| Catheter related infectionInfections and infestations | 0/30 | 2/31 | 0/31 |
| Urinary tract infectionInfections and infestations | 0/30 | 2/31 | 0/31 |
| Abdominal painGastrointestinal disorders | 1/30 | 1/31 | 1/31 |
| Idiopathic Thrombocytopenic PurpuraBlood and lymphatic system disorders | 1/30 | 0/31 | 0/31 |
| DepressionPsychiatric disorders | 1/30 | 0/31 | 0/31 |
| Event | hATG, CsA, EPAG Day 14 to Month 6 | hATG, CsA, EPAG Day 14 to Month 3 | hATG, CsA (Dose Reduced), EPAG Day 1 to Month 6 |
|---|---|---|---|
| Alanine aminotransferase increasedInvestigations | 3/30 | 8/31 | 11/31 |
| Blood bilirubin increasedInvestigations | 9/30 | 9/31 | 5/31 |
| Aspartate aminotransferase increasedInvestigations | 2/30 | 3/31 | 7/31 |
| Febrile neutropeniaBlood and lymphatic system disorders | 0/30 | 1/31 | 5/31 |
| Blood bilirubin increased (intermittent)Investigations | 2/30 | 4/31 | 1/31 |
| Abdominal painGastrointestinal disorders | 2/30 | 1/31 | 1/31 |
| Edema limbsGeneral disorders | 2/30 | 0/31 | 0/31 |
| Gastroesophageal reflux diseaseGastrointestinal disorders | 2/30 | 1/31 | 0/31 |
| HypokalemiaInvestigations | 0/30 | 0/31 | 2/31 |
| Skin hyperpigmentationSkin and subcutaneous tissue disorders | 0/30 | 0/31 | 2/31 |
| Age, Categorical(Participants) | hATG, CsA, EPAG Day 14 to Month 6 | hATG, CsA, EPAG Day 14 to Month 3 | hATG, CsA (Dose Reduced), EPAG Day 1 to Month 6 | Total |
|---|---|---|---|---|
| <=18 years | 5 | 6 | 8 | 19 |
| Between 18 and 65 years | 20 | 23 | 18 | 61 |
| >=65 years | 5 | 2 | 5 | 12 |
| Sex: Female, Male(Participants) | hATG, CsA, EPAG Day 14 to Month 6 | hATG, CsA, EPAG Day 14 to Month 3 | hATG, CsA (Dose Reduced), EPAG Day 1 to Month 6 | Total |
|---|---|---|---|---|
| Female | 14 | 14 | 14 | 42 |
| Male | 16 | 17 | 17 | 50 |
| Ethnicity (NIH/OMB)(Participants) | hATG, CsA, EPAG Day 14 to Month 6 | hATG, CsA, EPAG Day 14 to Month 3 | hATG, CsA (Dose Reduced), EPAG Day 1 to Month 6 | Total |
|---|---|---|---|---|
| Hispanic or Latino | 6 | 2 | 9 | 17 |
| Not Hispanic or Latino | 24 | 29 | 22 | 75 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | hATG, CsA, EPAG Day 14 to Month 6 | hATG, CsA, EPAG Day 14 to Month 3 | hATG, CsA (Dose Reduced), EPAG Day 1 to Month 6 | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 |
| Asian | 3 | 4 | 1 | 8 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 5 | 7 | 4 | 16 |
| White | 16 | 19 | 23 | 58 |
| More than one race | 3 | 0 | 3 | 6 |
| Unknown or Not Reported | 3 | 1 | 0 | 4 |
| Region of Enrollment(participants) | hATG, CsA, EPAG Day 14 to Month 6 | hATG, CsA, EPAG Day 14 to Month 3 | hATG, CsA (Dose Reduced), EPAG Day 1 to Month 6 | Total |
|---|---|---|---|---|
| United States | 30 | 31 | 31 | 92 |
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from Jul 2012 to primary completion in Jan 2018, 66 months.
Results were first posted in Jun 2020, 2 years 4 months after primary completion.
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