Efficacy of IST Combined With TPO-RA in the Treatment of AA and Establishment of a Recurrence Prediction System

Aplastic Anemia Clinical Trial

Official title:

Establishment of an Efficacy and Relapse Prediction System for Immunosuppressants Combined With Thrombopoietin Receptor Agonists in the Treatment of Aplastic Anemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06009965
• Other study ID #: SN-01
• Status: Recruiting
• Phase: Phase 4
• Start date: January 20, 2023
• Est. completion date: January 31, 2025

Study information

• Verified date: August 2023
• Source: Peking Union Medical College Hospital
• Contact: Yali Du, Master
• Phone: +8615845992396
• Email: yali_crazy[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In this study, investigators intend to prospectively study treatment-naive AA patients (including SAA and NSAA) who are non-transplant candidates in northern China. Patients with SAA receive ATG+CsA+Herombopag, and patients with NSAA receive CsA+ Herombopag. Investigators explored possible indicators of participants' predictive efficacy and built predictive models. After the participants achieved response, they used a tapering regimen, observed relapse and clonal evolution, and developed a predictive model of relapse.

Description:

1) Patients in the SAA group: CsA: 3-5mg/kg/day, monitor the trough concentration every month, and maintain the trough concentration at 100-200ng/ml. ATG: rabbit anti-thymocyte immunoglobulin (r-ATG) 3mg/kg/d×5 days, or porcine anti-lymphocyte immunoglobulin ((p-ATG) 25mg/kg/d×5 days; TPO-RA: Herombopag starts at 7.5 mg qd, monitor the blood picture every 2 weeks, if the effect is not good, add 1 tablet every 2 weeks, up to 6 tablets (15 mg) qd.

Patients in the NSAA group: CsA: 3-5mg/kg/day, monitor the trough concentration every month, and maintain the trough concentration at 100-200ng/ml. TPO-RA: start with 7.5mg qd of Herombopag, monitor the blood picture every 2 weeks, if the effect is not good, add 1 tablet every 2 weeks, up to 6 tablets (15mg) qd.

(2) Those who are effective after 6 months of treatment continue to receive sufficient CsA treatment for at least 1.5 years, and then slowly reduce the dose until the end of the reduction. Those who fail to withdraw from the clinical trial.

(3) Participants who achieve CR or PR after treatment, but when the curative effect does not increase after 3 months of maintenance treatment, start to reduce the dose of Herombopag, and reduce one tablet every 3 months until the reduction stops. If recurrence occurs, recover Up to the last dose or even increase the dose, after reaching the best curative effect, reduce one tablet every 3 months until the reduction stops, and those who cannot recover are defined as relapse.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 210
• Est. completion date: January 31, 2025
• Est. primary completion date: January 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Age: 18-75 years old, gender is not limited

2. Definite diagnosis of AA

3. No HSCT indication or unconditional HSCT

4. SAA/VSAA patients were willing to accept ATG+CsA+TPO-RA treatment, NSAA was willing to accept CsA+TPO-RA treatment, and were willing to follow up regularly

5. Baseline serum transaminase, total bilirubin and serum creatinine were less than 1.5 times the normal value

6. Baseline liver and kidney function was less than 1.5 times the normal value

7. Eastern Cancer Cooperation Group (ECOG) score status 0-2

8. Agree to sign the consent form

Exclusion Criteria:

1. Congenital AA

2. Cytogenetic evidence of clonal hematologic bone marrow disease

3. PNH clone =50%

4. Allergic to ATG, cyclosporine and hexapopal in the past

5. Uncontrolled infection or bleeding at enrollment

6. Received hematopoietic stem cell transplantation (HSCT) before enrollment

7. Any concomitant malignancy within 5 years, except for local skin basal cell carcinoma

8. A history of thromboembolic events, myocardial infarction, or stroke (including antiphospholipid antibody syndrome); Currently using anticoagulants

9. Pregnant or lactating women

10. Situations considered unsuitable for clinical research by other researchers

Related Conditions & MeSH terms

• Anemia
• Anemia, Aplastic
• Aplastic Anemia
• Drug Therapy

Intervention

Drug:
• CsA+ATG+Herombopag
CsA: 3-5 mg/kg/day, monitor trough concentration monthly, maintain trough concentration at 100-200 ng/ml.ATG: rabbit anti-thymocyte immunoglobulin (r-ATG) 3 mg/kg/d x 5 days or porcine anti-lymphocyte immunoglobulin ((p-ATG) 25 mg/kg/d x 5 days.TPO-RA: Heptapepto-Papa 7.5 mg qd to start. Monitor blood every 2 weeks and if ineffective, increase by 1 tablet every 2 weeks up to a maximum of 6 tablets (15mg) qd.
• CsA+Herombopag
CsA: 3-5 mg/kg/day, monitor trough concentrations monthly, maintain trough concentrations at 100-200 ng/ml.TPO-RA: Start with Hetropoxyphene 7.5 mg qd, monitor blood every 2 weeks, and if ineffective, increase by 1 tablet every 2 weeks up to a maximum of 6 tablets (15 mg) qd.

Locations

Country	Name	City	State
China	Peking union medical college hospital	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate	Overall response rate	24 weeks after treatment
Primary	24-month recurrence rate	.24-month recurrence rate	96 weeks after treatment
Secondary	Overall response rate	Overall response rate	56 weeks after treatment
Secondary	36-month recurrence rate	36-month recurrence rate	144 weeks after treatment