The Combination of ATRA and Eltrombopag as the Treatment of Steroid-resistant/Relapse ITP Based on MSC-C5b-9

Purpura, Thrombocytopenic, Idiopathic Clinical Trial

Official title:

The Combination of ATRA and Eltrombopag as the Treatment Strategy for Glucocorticoid-Resistant/Relapsed ITP Based on the Stratification of the New Biomarker MSC-C5b-9: A Prospective, Randomized, Open-Label, Multicenter Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05438875
• Other study ID #: 2022-1-4082
• Status: Recruiting
• Phase: Phase 3
• Start date: October 12, 2022
• Est. completion date: March 31, 2025

Study information

• Verified date: November 2023
• Source: Peking University People's Hospital
• Contact: Xiaohui Zhang, MD
• Phone: +8613522338836
• Email: zhangxh100[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A Prospective, Randomized, Open-Label, Multicenter Clinical Trial study to compare the efficacy and safety of ATRA plus eltrombopag compared to eltrombopag monotherapy in the treatment of steroid-resistant/relapsed immune thrombocytopenia (ITP).

Description:

The investigators are undertaking a parallel group, multicenter, randomized controlled trial of patients with ITP in China. Patients were tested for MSCs, and they were divided into MSC-C5b-9+ group and MSC-C5b-9- group according to the test results, and the two groups were randomized to ATRA + eltrombopag and eltrombopag monotherapy group. Platelet count, bleeding and other symptoms were evaluated before and after treatment. Adverse events are also recorded throughout the study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 96
• Est. completion date: March 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 1. Isolated thrombocytopenia (platelet count <30 × 109/L); 2. age > 18 years; 3. normal white blood cells and red blood cells on bone marrow examination; 4. increased number of megakaryocytes (bone marrow examination was performed in all patients except for myelofibrosis or other conditions that can cause thrombocytopenia disease); 5. the spleen was normal in size; 6. Eastern Cooperative Oncology Group status score (ECOG score) = 2; 7. ineffective or relapsed after at least 1 course of full-dose full-course hormone therapy; 8. Failure of prior ITP therapy (eg, hormones, splenectomy, and cyclosporine) and at least 4 weeks from enrollment.

Exclusion Criteria:

• 1. Secondary ITP such as drug-related thrombocytopenia; 2. thrombocytopenia due to viral infection (HIV, hepatitis B virus, or hepatitis C virus); 3. severe cardiac, renal, hepatic, or respiratory insufficiency; 4. severe immunodeficiency; 5. pregnancy or lactation; 6. myelodysplasia or Myelofibrosis; 7. history of malignancy; 8. ongoing immunosuppressive therapy for other diseases; 9. patients previously treated with eltrombopag were excluded from this study.

Related Conditions & MeSH terms

• Purpura
• Purpura, Thrombocytopenic
• Purpura, Thrombocytopenic, Idiopathic

Intervention

Drug:
• all-trans retinoic acid
ATRA 10 mg, 2 times a day, orally.The treatment course is 12 weeks.
• Eltrombopag
The initial dose of eltrombopag is 50 mg/time, once a day, and the dose is increased when the platelet count is lower than 5×109/L, the maximum is 75 mg/d, and the dose is higher than 200×109/L. When the drug is temporarily discontinued, the drug is re-administered according to the platelet count.The treatment course is 12 weeks.

Locations

Country	Name	City	State
China	Beijing Tongren hospital	Beijing	Beijing
China	Department of Hematology, Beijing Friendship Hospital, Capital Medical University	Beijing
China	Department of Hematology, Beijing Hospital	Beijing
China	Department of Hematology, Senior Department of Hematology, the Fifth Medical Center of PLA General Hospital	Beijing
China	Peking University Insititute of Hematology, Peking University People's Hospital	Beijing	Beijing

Sponsors (5)

Lead Sponsor	Collaborator
Peking University People's Hospital	Beijing Friendship Hospital, Beijing Hospital, Beijing Tongren Hospital, Navy General Hospital, Beijing

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sustained Response Rate (SR) at 18 months	The maintenance of platelet count = 30 x 10^9/L, at least 2-fold increase of the baseline count, the absence of bleeding, and no need for rescue medication at the 18-month follow-up	18 months
Secondary	Complete response rate (CR)	The complete response (CR) was defined as platelet count more than 100×10^9/L and absence of bleeding.	18 months
Secondary	Response rate (R)	The Response rate (R) was defined as platelet count more than 30×10^9/L and more than 2 times higher than baseline, without bleeding	18 months
Secondary	Inefficiency (NR)	Platelet count <30×10^9/L, or less than 2-fold increase from baseline or associated with bleeding	18 months
Secondary	Recurrence rate (relapse)	After the treatment is effective, the platelet count drops below 30×10^9/L or drops to less than 2 times the basal value, or bleeding symptoms occur	18 months
Secondary	Early response	Platelet count =30×10^9/L and at least doubling baseline at 1 wk.	1 week
Secondary	Initial response	Initial response as platelet count more than 30×10^9/L and at least 2-fold increase of the baseline count and absence of bleeding.	1 month
Secondary	Time to response (TTR)	The time from starting treatment to time of achievement of CR or R	18 months
Secondary	Time to relapse (duration of efficacy)	The time from achievement of CR or R to time of relapse	18 months