The Combination of Zanubrutinib and High-dose Dexamethasone as First-line Treatment in Adult Immune Thrombocytopenia

Study Overview
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Brief Summary
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Randomized, open-label, multicenter study to compare the efficacy and safety of zanubrutinib plus high-dose dexamethasone compared to high-dose dexamethasone monotherapy for the first-line treatment of adults with primary 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 randomized to Zanubrutinib + high-dose dexamethasone and high-dose dexamethasone 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 Oral Zanubrutinib and High-dose Dexamethasone vs High-dose Dexamethasone as First-line Treatment in Adult Immune Thrombocytopenia: A Multicenter, Randomized, Open-label Trial

Conditions
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Immune Thrombocytopenia

Intervention / Treatment
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* Drug: Zanubrutinib
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed newly-diagnosed, treatment-naive ITP; Platelet counts <30×10^9/L ; Platelet counts < 50×10^9/L and significant bleeding symptoms (WHO bleeding scale 2 or above); Willing and able to sign written informed consent. Exclusion Criteria: Received chemotherapy or anticoagulants or other drugs affecting the platelet counts within 6 months before the screening visit; Received first-line and second-line ITP-specific treatments (eg, steriods, cyclophosphamide, 6-mercaptopurine, vincristine, vinblastine, etc) ; Current HIV infection or hepatitis B virus or hepatitis C virus infections; Active infection; Maligancy; Severe medical condition (lung, hepatic or renal disorder) other than chronic ITP. Unstable or uncontrolled disease or condition related to or impacting cardiac function (e.g., unstable angina, congestive heart failure, uncontrolled hypertension or cardiac arrhythmia); Female patients who are nursing or pregnant, who may be pregnant, or who contemplate pregnancy during the study period; a history of clinically significant adverse reactions to previous corticosteroid therapy; Have a known diagnosis of other autoimmune diseases, established in the medical history and laboratory findings with positive results for the determination of antinuclear antibodies, anti-cardiolipin antibodies, lupus anticoagulant or direct Coombs test.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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 |
| --- | --- |
| Experimental: Zanubrutinib and HD-DXM<br>Dexamethasone 40 mg per day, 4 consecutive days (the 4-day course of dexamethasone was repeated in the case of lack of response by day 10) and Zanubrutinib 80mg qd po, 6 consecutive weeks | Drug: Zanubrutinib<br>* Zanubrutinib 80mg qd po, 6 consecutive weeks<br>* Other names: BTK inihibitor;Drug: Dexamethasone<br>* Dexamethasone, iv, 40 mg/d, for 4 days (The 4-day course of dexamethasone was repeated in the case of lack of response by day 10)<br>* Other names: HD-DXM;|
| Active Comparator: HD-DXM<br>Dexamethasone 40 mg per day, 4 consecutive days (the 4-day course of dexamethasone was repeated in the case of lack of response by day 10) | Drug: Dexamethasone<br>* Dexamethasone, iv, 40 mg/d, for 4 days (The 4-day course of dexamethasone was repeated in the case of lack of response by day 10)<br>* Other names: HD-DXM;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Initial complete response | Initial complete response (CR) was defined as platelet count more than 100,000 per cubic millimeter and absence of bleeding. | 1 month | 
| Initial response | Initial response (R) as platelet count more than 30,000 per cubic millimeter and at least 2-fold increase of the baseline count and absence of bleeding. | 1 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 | 
| Time to response (TTR) | The time from starting treatment to time of achievement of CR or R | 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 month | 
| Durable response | Platelet count ≥30 X 10^9/L and at least doubling of the baseline count at 6 mo | 6 months | 
| Early response | Platelet count ≥30 X 10^9/L and at least doubling baseline at 1 wk | 1 week | 
| Remission | Platelet count >100 X 10^9/L at 12 month | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BTK inhibitor, High-dose Dexamethasone