Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
Study -> Protocol Section -> Description Module
Description Module
Ignite Creation Date:
2025-12-25 @ 4:26 AM
Ignite Modification Date:
2025-12-25 @ 4:26 AM
NCT ID:
NCT04304820
Brief Summary:
Background:
Severe aplastic anemia (SAA) is a rare and serious blood disorder. It causes the immune system to turn against bone marrow cells. Standard treatment for SSA is a combination of 3 drugs (Cyclosporine \[CsA\], Eltrombopag \[EPAG\], and horse anti-thymocyte globulin \[h-ATG\]). Researchers want to see if starting people at a lower dose of CsA with EPAG before giving them h-ATG is helpful.
Objective:
To learn if early initiation of oral therapy with CsA and EPAG is safe and effective in people who have SAA and have not been treated with a course of immunosuppressive therapy and EPAG.
Eligibility:
People ages 3 and older with SAA
Design:
Participants will be screened with:
medical history
physical exam
electrocardiogram
blood tests
family history
bone marrow biopsy
current medicines.
Participants may be screened remotely via telephone conference.
Participants will take a lower oral dose of CsA and EPAG. They will take CsA twice a day for 6 months. They will take EPAG for 6 months. Those who cannot visit the NIH Clinical Center within 72 hours will start taking the drugs at home. They will have weekly telephone calls with NIH staff until they visit the Clinical Center.
Participants may get h-ATG at the Clinical Center for 4 days. For this, they will have a central line placed. It is a plastic tube inserted into a neck, chest, or arm vein.
Participants will repeat most screening tests throughout the study.
Participants will have follow-up visits at the Clinical Center at 3 months, 6 months, and annually for 5 years after the start of the study....
Detailed Description:
Severe aplastic anemia (SAA) is a life-threatening bone marrow failure characterized by pancytopenia and a hypocellular marrow. Allogeneic bone marrow transplantation is curative in younger patients, but older age and/or lack of a suitable donor have limited application of this procedure. As an alternative to transplant, immunosuppressive treatment (IST) has provided durable remissions and similar long term survival \[1\]. Approximately 2/3 of patients who receive IST with horse anti-thymocyte globulin (h-ATG) and cyclosporine (CsA) have blood count recovery, but 25-30% do not respond and 30-40% will relapse. A likely explanation for partial recovery and relapse is incomplete elimination of auto-reactive T cells and insufficient stem cell reserve.
Thrombopoietin (TPO) is a key regulator of hematopoietic stem cell renewal and survival. To improve the hematologic response rate, our group assessed the addition of eltrombopag (EPAG), a synthetic mimetic of TPO, to IST in treatment na(SqrRoot) ve SAA. This combination achieved a higher complete response rate to about 50% and an overall response rate to 80%, both superior to historic controls \[2\]. This regimen received FDA approval in November 2018. Combined therapy is now being tested in a European randomized study. Furthermore, protocols have been developed internationally to determine whether EPAG and CsA, without ATG, are sufficient to improve blood counts, in countries where ATG is not available.
The long-term complications, relapse and clonal evolution, were no worse with the addition of EPAG than in our historical cohort, but still remain a problem. Clonal evolution occurs in 10-15% of patients and is defined as development of myelodysplastic syndrome or acute myeloid leukemia with characteristic cytogenetic abnormalities of aneuploidy, especially monosomy 7 or deletion 7q. There are no predictive tools to identify patients at higher risk for either of these two long term events.
Because SAA is a rare disease, treatment has been recommended to take place at a specialized center. However, delays in reaching such centers and initiating therapy are common. From current understanding of the disease, immune destruction of cells is ongoing during this period, likely impacting on both short and long term outcomes. We propose early initiation of lower dose CsA (2mg/kg/day) and EPAG to decrease ongoing immune destruction and stimulate HSPC while awaiting full work up and transfer to the Clinical Center (CC).
The aim of this study is to test feasibility and safety of initiating oral therapy before arriving to the NIH, based on diagnostic tests performed by local physicians and interpretation from experts here. Treatment will be initiated remotely but under complete guidance and supervision of the research team at the Hematology Branch. All patients except the ones who achieve complete response will receive standard three drug regimen upon completion of work up here at the CC. Primary endpoint of the study will be to assess feasibility and safety as a composite measure of misdiagnosis, non-compliance with the regimen or failure to establish care at the Clinical Center within 8 weeks of initiating treatment, and TRSAE (treatment related serious adverse events). Initial treatment period
of 8 weeks may be extended in special circumstances. Secondary endpoints are response rates at landmark time points, relapse, overall survival, and clonal evolution.
Study:
NCT04304820
Study Brief:
Protocol Section:
NCT04304820