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

NCT04304820 | Recruiting Phase 2 Results FDA Drug

• 2 other identifiers: 20003320-H-0033
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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....

Conditions

Severe Aplastic Anemia

Keywords

Immunosuppression; T-cells; Hematopoiesis; Autoimmunity; Thrombocytopenia

Outcome Measures

Primary Outcomes (1)

• 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).

  Up to 12 Weeks from the initiation of oral treatment (Low Dose Cyclosporine and Eltrombopag)

Secondary Outcomes (6)

• Hematological Response

  At 1, 2, 3, 6 and 12 months and yearly thereafter

• Relapse

  At 1, 2, 3, 6 and 12 months and yearly thereafter

• Clonal Evolution to PNH, Clonal Chromosomal Population in Bone Marrow, Myelodysplasia by Morphology, or Acute Leukemia

  At 1, 2, 3, 6 and 12 months and yearly thereafter

• Overall Survival

  At 5 Years (60 Months)

• Hematological Response of Relapse Subjects That Re-start Treatment With Cyclosporine and/or Eltrombopag

  At 1, 2, 3, 6 and 12 months and yearly thereafter

Study Arms (2)

Participants with Severe Aplastic Anemia in Early Initiation of Cyclosporine and Eltrombopag

EXPERIMENTAL

Treatment-naïve Severe Aplastic Anemia (SAA) participants start Cyclosporine (CsA) on Day 1 at 2 mg/kg/day. At initiation of Horse Anti-Thymocyte-Globulin (h-ATG), dosing increases to 3 mg/kg every 12 hours for those ≥12 years (6 mg/kg/day total) and 6 mg/kg every 12 hours for those \<12 years (12 mg/kg/day total). Actual body weight is used unless \>125% ideal body weight (IBW), where adjusted IBW applies. CsA is titrated to a trough of 200-400 mcg/L. At 6 months, responders reduce to 2 mg/kg/day through 24 months, with return to full dosing if relapse occurs. h-ATG is given at 40 mg/kg/day for 4 days IV, unless the patient already shows a complete response at the initial NIH visit after remote oral therapy. Eltrombopag (EPAG) starts on Day 1 at 150 mg/day for ages 12-17, 75 mg/day for ages 6-11, and 2.5 mg/kg/day for ages 3-5. For East and Southeast Asian patients, starting doses are reduced to 75 mg/day (ages 12-85), 37.5 mg/day (ages 6-11), and 1.25 mg/kg/day (ages 3-5).

Drug: Eltrombopag; Drug: Cyclosporine; Drug: Horse-Anti-thymocyte-Globulin

Extension Cohort

EXPERIMENTAL

Treatment-naïve Severe Aplastic Anemia (SAA) participants start Cyclosporine (CsA) on Day 1 at 2 mg/kg/day. At initiation of Horse Anti-Thymocyte-Globulin (h-ATG), dosing increases to 3 mg/kg every 12 hours for those ≥12 years (6 mg/kg/day total) and 6 mg/kg every 12 hours for those \<12 years (12 mg/kg/day total). Actual body weight is used unless \>125% ideal body weight (IBW), where adjusted IBW applies. CsA is titrated to a trough of 200-400 mcg/L. At 6 months, responders reduce to 2 mg/kg/day through 24 months, with return to full dosing if relapse occurs. h-ATG is given at 40 mg/kg/day for 4 days IV, unless the patient already shows a complete response at the initial NIH visit after remote oral therapy. Eltrombopag (EPAG) starts on Day 1 at 150 mg/day for ages 12-17, 75 mg/day for ages 6-11, and 2.5 mg/kg/day for ages 3-5. For East and Southeast Asian patients, starting doses are reduced to 75 mg/day (ages 12-85), 37.5 mg/day (ages 6-11), and 1.25 mg/kg/day (ages 3-5).

Drug: Eltrombopag; Drug: Cyclosporine; Drug: Horse-Anti-thymocyte-Globulin

Interventions

Eltrombopag DRUG

Between 12 and 17yo (adult dose of 150mg) Between 6 and 11yo (75 mg) Between 3 and 5 yo (2.5 mg/kg)

Also known as: EPAG

Extension Cohort; Participants with Severe Aplastic Anemia in Early Initiation of Cyclosporine and Eltrombopag

Cyclosporine DRUG

Day 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

Also known as: CsA

Extension Cohort; Participants with Severe Aplastic Anemia in Early Initiation of Cyclosporine and Eltrombopag

Horse-Anti-thymocyte-Globulin DRUG

h-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

Also known as: H-ATG

Extension Cohort; Participants with Severe Aplastic Anemia in Early Initiation of Cyclosporine and Eltrombopag

Eligibility Criteria

• Age: 3 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>= 3 years old
• Weight \>12Kg
• 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

You may not qualify if:

• 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
• Subjects with liver cirrhosis (as determined by the investigator).
• 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.
• Glomerular filtration rate (GFR) \<40 mL/min/1.73m\^2
• Hypersensitivity to EPAG or its components
• Infection not adequately responding to appropriate therapy
• 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
• Potential subjects with cancer who are on active chemotherapeutic treatment or who take drugs with hematological effects will not be eligible
• 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.
• Inability to swallow
• Unable to participate in audio/video telecommunication
• Inability to ship the study drug to participant

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Anemia, Aplastic; Autoimmune Diseases; Thrombocytopenia

Interventions

eltrombopag; Cyclosporine; Antilymphocyte Serum

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases; Immune System Diseases; Blood Platelet Disorders; Cytopenia

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Bhavisha Patel, M.D.
• Organization: National Heart, Lung and Blood Institute (NHLBI)

bhavisha.patel@nih.gov

301-402-3477

Study Officials

• Bhavisha A Patel, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Olga J Rios, R.N.

CONTACT

(301) 496-4462; olga.rios@nih.gov

Bhavisha A Patel, M.D.

CONTACT

(301) 402-3477; bhavisha.patel@nih.gov

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2020
• First Posted: March 11, 2020
• Study Start: May 7, 2020
• Primary Completion: December 18, 2024
• Study Completion (Estimated): December 18, 2033
• Last Updated: March 9, 2026
• Results First Posted: January 9, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Starting approximately 6 months after publication and available indefinitely.
• Access Criteria: Data may be shared through an open or closed repository as appropriate.

Locations

US (1)