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

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

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).

Study Overview

• Status: Completed
• Conditions: Purpura, Thrombocytopenic, Idiopathic
• Intervention / Treatment: Drug: Eltrombopag; Drug: all-trans retinoic acid

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • 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 Municipality
    • Beijing, Beijing Municipality, China, 100010
      • Peking University Insititute of Hematology, Peking University People's Hospital
    • Beijing, Beijing Municipality, China
      • Beijing Tongren Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Eltrombopag; The initial dose of eltrombopag was 50 mg/time, once a day. According to the clinical standard of eltrombopag dose adjustment in the research protocol set by the research group, the dose was increased when the platelet count was lower than 5×109/L. The highest is 75mg/d, if the dose is higher than 200×109/L, the dose is reduced. When the dose is higher than 400×109/L, the drug is temporarily discontinued, and the drug is repeated according to the platelet count. The treatment course is 12 weeks.	Drug: 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.; Other Names: TPO-RA
Experimental: ATRA and Eltrombopag; ATRA 10 mg, 2 times a day, orally; The initial dose of eltrombopag was 50 mg/time, once a day. According to the clinical standard of eltrombopag dose adjustment in the research protocol set by the research group, the dose was increased when the platelet count was lower than 5×109/L. The maximum dose is 75 mg/d, the dose is reduced if it is higher than 200×109/L, and the drug is temporarily discontinued when it is higher than 400×109/L, and the drug is repeated according to the platelet count. The treatment course is 12 weeks.	Drug: 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.; Other Names: TPO-RA; Drug: all-trans retinoic acid; ATRA 10 mg, 2 times a day, orally.The treatment course is 12 weeks.; Other Names: retinoic acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Inefficiency (NR)	Platelet count <30×10^9/L, or less than 2-fold increase from baseline or associated with bleeding	18 months
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
Early response	Platelet count ≥30×10^9/L and at least doubling baseline at 1 wk.	1 week
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
Time to response (TTR)	The time from starting treatment to time of achievement of CR or R	18 months
Time to relapse (duration of efficacy)	The time from achievement of CR or R to time of relapse	18 months

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Collaborators: Beijing Friendship Hospital; Beijing Tongren Hospital; Beijing Hospital; Navy General Hospital, Beijing
• Investigators: Principal Investigator: Xiaohui Zhang, MD, Study Principal Investigator Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2022
• Primary Completion (Actual): November 30, 2024
• Study Completion (Actual): November 30, 2024

Study Registration Dates

• First Submitted: June 25, 2022
• First Submitted That Met QC Criteria: June 25, 2022
• First Posted (Actual): June 30, 2022

Study Record Updates

• Last Update Posted (Estimated): September 9, 2025
• Last Update Submitted That Met QC Criteria: September 2, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Eltrombopag; all-trans retinoic acid; prospective clinical study; Resistant/recurrent ITP; MSC-C5b-9 marker
• Additional Relevant MeSH Terms: Cytopenia; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Skin Manifestations; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura, Thrombocytopenic; Purpura; Thrombocytopenia; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hemic and Lymphatic Diseases; Purpura, Thrombocytopenic, Idiopathic; Organic Chemicals; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Pigments, Biological; Biological Factors; Diterpenes; Vitamin A; Tretinoin; eltrombopag
• Other Study ID Numbers: 2022-1-4082

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No