Early Initiation of Oral Therapy With Cyclosporine and Eltrombopag for Treatment Naive Severe Aplastic Anemia (SAA)

• Status: Recruiting
• Trial end date: 2027-05-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Antilymphocyte Serum; Cyclosporine; Cyclosporins

Criteria

• INCLUSION CRITERIA:

1. Age >= 3 years old

2. Weight >12Kg

3. Severe aplastic anemia:

• Bone marrow cellularity <30% (excluding lymphocytes) AND At least two of the following:

• Absolute neutrophil count <500/microliter

• Platelet count <20,000/microliter

• Absolute reticulocyte count <60,000/microliter

EXCLUSION CRITERIA:

1. Known diagnosis or high suspicion of Fanconi anemia or other constitutional marrow failure syndrome

2. 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

3. A course of prior immunosuppressive therapy (ATG, cyclosporine, alemtuzumab, and high dose cyclophosphamide), or eltrombopag

4. SGOT or SGPT >2.5 times the upper limit of normal or total bilirubin >1.5 x upper limit of normal

5. Subjects with liver cirrhosis (as determined by the investigator).

6. Subjects with human immunodeficiency virus (HIV) who are not receiving antiretroviral therapy, have detectable HIV RNA viral load and have CD4 cell count <200/microliter, or are on anti-retroviral therapy that interacts with the study drugs. subjects will not be excluded if HIV testing is pending or unavailable.

7. Glomerular filtration rate (GFR) <40 mL/min/1.73m^2

8. Hypersensitivity to EPAG or its components

9. Infection not adequately responding to appropriate therapy

10. 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

11. Potential subjects with cancer who are on active chemotherapeutic treatment or who take drugs with hematological effects will not be eligible

12. 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.

13. Inability to swallow

14. Unable to participate in audio/video telecommunication

15. Inability to ship the study drug to participant

16. History or current diagnosis of cardiac disease indicating significant risk of safety for patients participating in the study such as uncontrolled or significant cardiac disease,

including any of the following: Recent myocardial infarction (within last 6 months), uncontrolled congestive heart failure, unstable angina (within last 6 months), clinically significant (symptomatic) cardiac arrhythmias (e.g., sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker.), long QT

syndrome, family history of idiopathic sudden death, congenital long QT syndrome or additional risk factors for cardiac repolarization abnormality, as determined by the investigator.

17. Impaired cardiac function, such as: Corrected QTc >450 msec using Fridericia correction (QTcF) on the screening ECG (using triplicate ECGs), other clinically significant cardiovascular disease (e.g., uncontrolled hypertension, history of labile hypertension), history of known structural abnormalities (e.g. cardiomyopathy).

18. Concurrent participation in an investigational study within 30 days prior to enrollment or within 5-half-lives of the investigational product, whichever is longer. Note: parallel enrollment in a disease registry is permitted.

19. Known thrombophilic risk factors. Exception: Subjects for whom the potential benefits of participating in the study outweigh the potential risks of thromboembolic events, as determined by the investigator.

20. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using basic methods of contraception during dosing of study treatment. Basic contraception methods include:

• Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation

methods) and withdrawal are not acceptable methods of contraception

• Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment

• Male sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that subject

• Barrier methods of contraception: Condom or Occlusive cap. For the UK: with spermicidal foam/gel/film/cream/ vaginal suppository

• Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception.

• In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment.

21. Female subjects who are nursing or pregnant (positive serum or urine B-human chorionic gonadotrophin (B-hCG) pregnancy test) at screening or pre-dose on Day 1

22. Sexually active males unless they use a condom during intercourse while taking the drug during treatment, and for 7 days after stopping treatment (and for an additional 12 weeks [for genotoxic compounds]) and should not father a child in this period. A condom is required to be used also by vasectomized men as well as during intercourse with a male partner in order to prevent delivery of the drug via semen.