Zanubrutinib and Eltrombopag as Second-line Treatment in Adults With Primary Immune Thrombocytopenia

Study Overview
=================
Brief Summary
-----------------
Randomized, open-label, multicenter study to compare the efficacy and safety of zanubrutinib plus eltrombopag compared to eltrombopag monotherapy for the first-line treatment of adults with chronic immune thrombocytopenia (ITP).

Detailed Description
-----------------
The investigators are undertaking a prospective trial of patients with ITP in China. Zanubrutinib is administered as 80 mg po. qd for 6 weeks. Eltrombopag is given with 50 mg once daily for up to 6 weeks. Platelet count, bleeding and other symptoms were evaluated before and after treatment. Adverse events are also recorded throughout the study. This study assessed the efficacy and safety of eltrombopag plus zanubrutinib.

Official Title
-----------------
Zanubrutinib and Eltrombopag as Second-line Treatment for Patients With Immune Thrombocytopenia: a Multicentre, Open-label,Randomised, Controlled, Phase 2 Trial

Conditions
-----------------
Immune Thrombocytopenia

Intervention / Treatment
-----------------
* Drug: Zanubrutinib
* Drug: Eltrombopag


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Primary immune thrombocytopenia (ITP) confirmed by excluding other supervened causes of thrombocytopenia; Patients with chronic low platelet count (less than 30,000/µL) for 6 months who have failed at least one treatment for chronic low platelet count 2. Patients who did not achieve a sustained response to treatment with full-dose corticosteroids for a minimum duration of 4 weeks or who relapsed during steroid-tapering or after its discontinuation 3. Willing and able to sign written informed consent Exclusion Criteria: Secondary immune thrombocytopenia (e.g., patients with HIV, HCV, Helicobacter pylori infection or patients with systemic lupus erythematosus) congestive heart failure severe arrhythmia nursing or pregnant women aspartate aminotransferase and alanine transaminase levels ≥ 3× the upper limit of the normal threshold criteria creatinine or serum bilirubin levels each 1•5 times or more than the normal range active or previous malignancy Unable to do blood routine test for the sake of time, distance, economic issues or other reasons History of clotting disorder

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zanubrutinib and eltrombopag<br>Zanubrutinib 80mg po qd 6 weeks and eltrombopag 50 mg qd for up to 6 weeks. | Drug: Zanubrutinib<br>* Zanubrutinib 80mg po qd 6 weeks<br>* Other names: BTK inihibitor;Drug: Eltrombopag<br>* eltrombopag 50 mg qd for up to 6 weeks. The eltrombopag dose could be increased from 50 mg to 75 mg after 3 weeks in patients whose platelet counts were less than 50 000 per μL. Treatment was discontinued in patients who attained a platelet count greater than 200 000 per μL.<br>|
| Active Comparator: Eltrombopag monotherapy<br>Eltrombopag is given as 50 mg qd for up to 6 weeks. | Drug: Eltrombopag<br>* eltrombopag 50 mg qd for up to 6 weeks. The eltrombopag dose could be increased from 50 mg to 75 mg after 3 weeks in patients whose platelet counts were less than 50 000 per μL. Treatment was discontinued in patients who attained a platelet count greater than 200 000 per μL.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment response | The proportion of patients who had an increase in platelet counts to 50 000 per μL or more after 6 weeks of treatment | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response | 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 after 6 weeks of treatment | 6 weeks | 
| Complete response (CR) | Complete response (CR) was defined as platelet count more than 100,000 per cubic millimeter and absence of bleeding | 6 weeks | 
| Time to response | The time from starting treatment to time of achievement of Response | 6 weeks | 
| Sustained response | 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 12-month follow-up | 12 month | 
| Number of patients with bleeding | Number of patients with bleeding complication ( WHO bleeding score) | 12 months | 
| Number of patients with adverse events | Number of patients with adverse events | 12 months | 
| Duration of response (DOR) | Duration of response at 12-month follow up | 12 months | 
| Loss of response | Platelet counts below 100 x 109/L or bleeding (from CR) or platelet counts below 30 x 109/L, less than 2-fold increase of baseline platelet count or bleeding (from R) | 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
BTK inhibitor, Thrombopoietin-receptor agonist