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

Thrombocytopenia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05411874
• Other study ID #: ITP-Chidamide plus DEX
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: October 1, 2022
• Est. completion date: October 30, 2024

Study information

• Verified date: June 2022
• Source: Shandong University
• Contact: Ming Hou, Doctor
• Email: houming[@]medmail.com.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: October 30, 2024
• Est. primary completion date: October 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Thrombocytopenia

Intervention

Drug:
• Chidamide
5mg po biw for 24 weeks
• HD-DXM
40mg po qd for 4days

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Shandong University

References & Publications (2)

Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB, Chong BH, Cines DB, Gernsheimer TB, Godeau B, Grainger J, Greer I, Hunt BJ, Imbach PA, Lyons G, McMillan R, Rodeghiero F, Sanz MA, Tarantino M, Watson S, Young J, Kuter DJ. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010 Jan 14;115(2):168-86. doi: 10.1182/blood-2009-06-225565. Epub 2009 Oct 21. Review. — View Citation

Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, Bussel JB, Cines DB, Chong BH, Cooper N, Godeau B, Lechner K, Mazzucconi MG, McMillan R, Sanz MA, Imbach P, Blanchette V, Kühne T, Ruggeri M, George JN. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009 Mar 12;113(11):2386-93. doi: 10.1182/blood-2008-07-162503. Epub 2008 Nov 12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Time to response	The time from starting treatment to time of achievement of CR or R	6 month
Secondary	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 × 10? cells per L; measured on two occasions more than 1 day apart or the presence of bleeding).	6 month
Secondary	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