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....
Age >= 3 years old
Weight >12Kg
Absolute neutrophil count <500/microliter
Platelet count <20,000/microliter
Known diagnosis or high suspicion of Fanconi anemia or other constitutional marrow failure syndrome
Evidence of a clonal disorder on cytogenetics performed within 12 weeks of study entry involving chromosome 7 or complex karyotype. Patient will not be excluded if cytogenetics are not done or are pending
A course of prior immunosuppressive therapy (ATG, cyclosporine, alemtuzumab, and high dose cyclophosphamide), or eltrombopag
SGOT or SGPT >2.5 times the upper limit of normal or total bilirubin >1.5 x upper limit of normal
Single group
Eltrombopag
DrugBetween 12 and 17yo (adult dose of 150mg) Between 6 and 11yo (75 mg) Between 3 and 5 yo (2.5 mg/kg)
Cyclosporine
DrugDay 1 to start of h-ATG: 2mg/kg/day by mouth (All subjects) Start of h-ATG to Month 6: 3 mg/kg/dose by mouth administered every 12 hours (12yo and above) 6 mg/kg/dose by mouth administered every 12 hours (less than 12yo) Month 6 to Month 24: Dosing to be adjusted based on response
Horse-Anti-thymocyte-Globulin
Drugh-ATG at a dose of 40 mg/kg/day for 4 days (intravenously for approximately 4 hours daily) Note: Omitted in patients who have achieved a complete response at the initial NIH visit after initiating oral treatment remotely
Number of Participants Meeting Safety and Feasibility Criteria During Study Treatment Period With Oral Treatment (Low Dose Cyclosporine and Eltrombopag) Until the Start of Standard of Care Treatment (Horse Anti-thymocyte-globulin)
For the primary endpoint of this study, the treatment is defined to be "feasible" to a participant if he/she meets the safety and feasibility criteria. Safety and feasibility criteria is a composite measure defined as TRSAE, mis- and altered diagnosis, and non-compliance with the regimen or failure to establish care at the National Institutes of Health Clinical Center. Study treatment period is defined as the duration from the initiation of oral treatment (low dose Cyclosporine and Eltrombopag) to the start of standard of care treatment (Day 1 of horse anti-thymocyte-globulin).
Hematological Response
Relapse
Clonal Evolution to PNH, Clonal Chromosomal Population in Bone Marrow, Myelodysplasia by Morphology, or Acute Leukemia
Overall Survival
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