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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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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

Conditions
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Purpura, Thrombocytopenic, Idiopathic

Intervention / Treatment
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* Drug: all-trans retinoic acid
* Drug: Eltrombopag


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Eltrombopag<br>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<br>* 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.<br>* Other names: TPO-RA;|
| Experimental: ATRA and Eltrombopag<br>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: all-trans retinoic acid<br>* ATRA 10 mg, 2 times a day, orally.The treatment course is 12 weeks.<br>* Other names: retinoic acid;Drug: Eltrombopag<br>* 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.<br>* Other names: TPO-RA;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Resistant/recurrent ITP, MSC-C5b-9 marker, all-trans retinoic acid, Eltrombopag, prospective clinical study