Cyclosporine + Eltrombopag for Aplastic Anemia
Palo Alto (17 mi)Age: Any Age
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?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....
Do I have to stop taking my current medications for the trial?The trial protocol does not specify if you must stop taking your current medications. However, if you are on active chemotherapeutic treatment or drugs with hematological effects, you will not be eligible. It's best to discuss your current medications with the trial team.
Is the drug combination of Cyclosporine and Eltrombopag promising for treating Aplastic Anemia?Yes, the combination of Cyclosporine and Eltrombopag is promising for treating Aplastic Anemia. Research shows that Eltrombopag, when added to standard treatments like Cyclosporine, can improve the effectiveness of therapy for patients with severe aplastic anemia. This combination has shown positive results in several studies, suggesting it could be a beneficial option for patients.23458
What data supports the idea that Cyclosporine + Eltrombopag for Aplastic Anemia is an effective treatment?The available research shows that adding Eltrombopag to Cyclosporine improves the effectiveness of standard treatments for severe aplastic anemia. One study found that Eltrombopag increased the success of immunosuppressive therapy, which includes Cyclosporine and horse antithymocyte globulin. Another review highlighted that Eltrombopag is effective in increasing blood cell counts, which is crucial for patients with aplastic anemia. Additionally, a real-world study compared the combination of Cyclosporine and Eltrombopag with or without another drug, showing positive results in treating aplastic anemia. Overall, these studies suggest that the combination of Cyclosporine and Eltrombopag is an effective treatment for aplastic anemia.13578
What safety data is available for the treatment of cyclosporine and eltrombopag in aplastic anemia?The combination of eltrombopag and cyclosporine has been studied for its safety and efficacy in treating aplastic anemia. Eltrombopag is generally well tolerated, with increased liver transaminases as the only dose-limiting toxicity. In a retrospective study, mild adverse reactions were reported in some patients, but these were manageable. Clonal cytogenetic abnormalities were observed in 19% of patients and dysplasia in 5% of patients treated with eltrombopag. The combination of eltrombopag with cyclosporine is considered effective and has shown a good safety profile in patients with transfusion-dependent non-severe aplastic anemia.13678
Eligibility Criteria
This trial is for people aged 3 and older with severe aplastic anemia, a condition where the bone marrow doesn't make enough blood cells. Participants must have specific low blood cell counts, weigh over 12Kg, and not have HIV, certain infections or cancers, heart issues, liver cirrhosis or be on conflicting medications. Pregnant women or those who can't use contraception are excluded.Inclusion Criteria
I am at least 3 years old.
Exclusion Criteria
I cannot swallow.
I am not pregnant or nursing.
I do not have serious heart conditions or recent heart issues.
The study drug cannot be shipped to me.
I have liver cirrhosis.
I use a highly effective form of birth control.
I understand the study's purpose and can give informed consent.
I do not have heart issues like uncontrolled high blood pressure or a history of heart disease.
I am currently on chemotherapy or medication affecting my blood.
My kidney function is reduced with a GFR less than 40 mL/min.
I have or am suspected to have Fanconi anemia or a similar bone marrow failure condition.
My tests show a genetic issue with chromosome 7 or a complex genetic pattern.
I have risk factors for blood clots.
My infection is not getting better despite treatment.
I have HIV and either not on treatment, have a low CD4 count, or my treatment interacts with the study drugs.
I have previously received immunosuppressive therapy or eltrombopag.
Treatment Details
The study tests if starting oral Cyclosporine (CsA) and Eltrombopag (EPAG) early before horse anti-thymocyte globulin (h-ATG) helps treat severe aplastic anemia. Patients take CsA twice daily and EPAG for six months; some may receive h-ATG at NIH Clinical Center.
1Treatment groups
Experimental Treatment
Group I: SAAExperimental Treatment3 Interventions
Subjects with SAA treated with early initiation of oral treatment
Cyclosporine is already approved in European Union, United States, Canada, Japan for the following indications:
🇪🇺 Approved in European Union as Neoral for:
- Prevention of organ rejection in kidney, liver, heart, lung, pancreas, and bone marrow transplants
- Treatment of severe psoriasis
- Treatment of nephrotic syndrome
🇺🇸 Approved in United States as Neoral for:
- Prevention of organ rejection in kidney, liver, and heart transplants
- Treatment of severe rheumatoid arthritis
- Treatment of severe psoriasis
🇨🇦 Approved in Canada as Neoral for:
- Prevention of organ rejection in kidney, liver, heart, lung, pancreas, and bone marrow transplants
- Treatment of severe psoriasis
- Treatment of nephrotic syndrome
🇯🇵 Approved in Japan as Neoral for:
- Prevention of organ rejection in kidney, liver, and heart transplants
- Treatment of severe rheumatoid arthritis
- Treatment of severe psoriasis
Find a clinic near you
Research locations nearbySelect from list below to view details:
National Institutes of Health Clinical CenterBethesda, MD
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Who is running the clinical trial?
National Heart, Lung, and Blood Institute (NHLBI)Lead Sponsor
References
Eltrombopag: a review of its use in patients with severe aplastic anaemia. [2018]Eltrombopag (Promacta®) is an orally active thrombopoietin receptor agonist recently approved in the US for the treatment of patients with severe aplastic anaemia who have had an insufficient response to immunosuppressive therapy. This article reviews the efficacy and tolerability of eltrombopag in this indication and overviews its pharmacological properties. Eltrombopag does not compete with thrombopoietin and binds to a different site on the receptor, producing additive effects. It stimulates haematopoietic stem cells and promotes haematopoietic recovery in patients with aplastic bone marrow. Eltrombopag increased platelet counts and can also increase red blood cell and neutrophil counts. In patients with severe aplastic anaemia refractory to prior immunosuppressive therapy, oral eltrombopag at dosages ≤150 mg once daily for 12-16 weeks produced a haematological response in at least one cell lineage in 40 % of patients. Trilineage responses were achieved in nearly one-half of the responders during extended treatment. In robust responders, stable haematological counts were maintained after eltrombopag discontinuation. Eltrombopag was generally well tolerated, with increased liver transaminases as the only dose-limiting toxicity. Clonal cytogenetic abnormalities were observed in 19 % of patients and dysplasia in 5 % of patients.
Effect of cyclosporine coadministration on the pharmacokinetics of eltrombopag in healthy volunteers. [2019]Eltrombopag is indicated in patients with severe aplastic anemia (SAA) refractory to prior immunosuppressive therapy. The combination of eltrombopag and immunosuppressive therapy (such as cyclosporine) is currently being evaluated in patients with treatment-naive SAA. Cyclosporine is a human breast cancer resistance protein (BCRP) inhibitor, and can potentially alter plasma exposure to eltrombopag, a BCRP substrate. This phase 1, open-label, randomized, 3-period, crossover study evaluated the effect of cyclosporine on the pharmacokinetics of eltrombopag in healthy adults.
Efficacy and Safety of Eltrombopag for Aplastic Anemia: A Systematic Review and Meta-analysis. [2022]Eltrombopag seems to be effective in treating patients with aplastic anemia in several clinical trials. This paper aims to perform the first meta-analysis analyzing the efficacy and safety of eltrombopag for aplastic anemia.
Eltrombopag in children with severe aplastic anemia. [2022]Immunosuppressive therapy with horse antithymocyte globulin and cyclosporine currently remains the standard therapy for children with severe aplastic anemia (SAA) who lack human leukocyte antigen (HLA)-identical sibling. The thrombopoietin receptor agonist eltrombopag has been recently approved for SAA patients 2 years and older. However, there are limited data on its safety and efficacy in pediatric cohorts.
Eltrombopag Added to Immunosuppression in Severe Aplastic Anemia. [2023]A single-group, phase 1-2 study indicated that eltrombopag improved the efficacy of standard immunosuppressive therapy that entailed horse antithymocyte globulin (ATG) plus cyclosporine in patients with severe aplastic anemia.
[The efficacy of eltrombopag plus cyclosporine A in patients with transfusion-dependent non-severe aplastic anemia: a retrospective study from single center]. [2022]The main purpose of our study was to evaluate the efficacy and safety of eltrombopag plus cyclosporine A (CsA) in transfusion-dependent non-severe aplastic anemia(TD-NSAA). The clinical characteristics of 13 TD-NSAA patients who received initial treatment of eltrombopag plus CsA from 2019 to 2021 were retrospectively analyzed. The 3-month overall hematological response (OR) rate was 12/13. Until the end of follow-up, 12 patients responded, among whom 2 patients reached complete response (CR) and 9 patients reached partial response (PR) and 1 with HR. Paroxysmal nocturnal hemoglobinuria (PNH) developed in one patient at 6 months after treatment. Five of thirteen patients reported mild adverse reactions, which were all manageable. Compared with historical data, the combination of eltrombopag with CsA is an effective regimen in patients with TD-NSAA.
Cyclosporine plus eltrombopag in the treatment of aplastic anemia with or without antithymocyte immunoglobulin: A multicenter real-world retrospective study. [2023]To compare cyclosporine (CSA) combining eltrombopag (EPAG) with or without antithymocyte globulin (ATG) in aplastic anemia (AA) patients in the real world.
[Effect of Eltrombopag on Response to Immunosuppressive Therapy in Patients with Transfusion-Dependent Non-Severe Aplastic Anemia]. [2023]To compare the efficacy of eltrombopag combined with cyclosporine A (CsA) and CsA alone in patients with transfusion-dependent non-severe aplastic anemia (TD-NSAA).