A Multicenter Randomized Open-label Study of Chidamide Plus HD-DEX Versus HD-DEX in ITP

Study Overview
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Brief Summary
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Recently, histone deacetylase inhibitors (HDACi) has been used for their anti-inflammatory and immunomodulatory activities. It has been shown that HDACi can alleviate graft-versus-host disease by enhancing the number and function of Foxp3+ Tregs. Our group found that low-dose HDACi alleviated thrombocytopenia in both passive and active murine models of ITP. Furthermore, low-dose HDACi attenuated macrophage phagocytosis of antibody-coated platelets, stimulated production of natural Foxp3+ Tregs, promoted peripheral conversion of T cells into Tregs, and restored Treg suppressive function in vivo and in vitro. The project was undertaking by Qilu Hospital of Shandong University and other 10 well-known hospitals in China. In order to report the efficacy and safety of the low dose chidamide combined with high-dose dexamethasone versus high-dose dexamethasone in the management of ITP.

Detailed Description
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Primary immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with low platelet count. Low-dose HDACi alleviated thrombocytopenia in both passive and active murine models of ITP. In this multicentre, open-label, randomized controlled trial, newly diagnosed ITP patients will be enrolled from 11 tertiary medical centres in China. Participants will be randomly assigned into the combination group or the monotherapy group by masked statisticians in a 1:1 ratio. The primary endpoints are sustained response at month 6. The secondary outcomes include initial response, time to response, duration of response, bleeding score, health-related quality of life assessment, and safety issue. This study will compare the efficacy and safety of low dose chidamide combined with high-dose dexamethasone versus high-dose dexamethasone monotherapy in adults with primary immune thrombocytopenia.

Official Title
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A Multicenter Randomized Open-label Study of Chidamide Combined With High-dose Dexamethasone Versus High-dose Dexamethasone in the Management of Newly-Diagnosed Immune Thrombocytopenia

Conditions
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Thrombocytopenia

Intervention / Treatment
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* Drug: Chidamide
* Drug: HD-DXM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: newly diagnosed ITP patients need of treatment(s) to minimize the risk of clinically significant bleeding primary ITP confirmed by excluding other supervened causes of thrombocytopenia Exclusion Criteria: pregnancy hypertension cardiovascular disease diabetes liver and kidney function impairment HCV, HIV, HBsAg seropositive status patients with systemic lupus erythematosus and/or antiphospholipid syndrome

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: Chidamide plus HD-DXM<br>Chidamide (orally at 5 mg biw for 24 weeks) HD-DXM (orally at 40 mg daily for 4 days) | Drug: Chidamide<br>* 5mg po biw for 24 weeks<br>Drug: HD-DXM<br>* 40mg po qd for 4days<br>|
| Active Comparator: HD-DXM<br>HD-DXM (orally at 40 mg daily for 4 days ) | Drug: HD-DXM<br>* 40mg po qd for 4days<br>|

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 6-month follow-up. | 6 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Initial response | CR: platelet count ≥ 100 × 109/L and absence of bleeding; R: platelet count ≥ 30 × 109/L but < 100 × 109/L and a doubling from baseline and absence of bleeding. | day 14 | 
| Number of patients with bleeding | Number of patients with bleeding complication. Bleeding symptoms were graded according a standardized bleeding scale specific to primary immune thrombocytopenia on the basis of site and severity of bleeding by Khellaf et al (PMID: 15951296). A modification was made to exclude age from the original scale so that only bleeding symptoms were described. Scores ranged from 0 to 59, with higher values indicating higher bleeding risk. | 6 month | 
| Number of patients with adverse events | Adverse events were graded according to the Common Terminology Criteria for Adverse Events (version 4.0). At each visit, we recorded adverse events. Routine visits were scheduled once a week for the first 4 weeks and once a month thereafter. | 6 month | 
| Time to response | The time from starting treatment to time of achievement of CR or R | 6 month | 
| Duration of response (DOR) | Duration of response was defined as the time from achievement of a complete response or a partial response to the loss of response (platelet count <30 × 10⁹ cells per L; measured on two occasions more than 1 day apart or the presence of bleeding). | 6 month | 
| Health-related quality of life assessment | Health-related quality of life was assessed using a self-administered immune thrombocytopenia Patient Assessment Questionnaire (ITP-PAQ) at baseline and at week 12. Scores ranged from 0 to 100, with higher values indicating better quality of life. | 6 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HD-DEX, Chidamide