A Single-center Clinical Trial of Bortezomib in Management of Immune Thrombocytopenia (ITP)

Immune Thrombocytopenia Clinical Trial

— ITP  

Official title:

A Single-center Clinical Trial of Bortezomib in Management of Immune Thrombocytopenia (ITP) With High Anti-platelet Antibodies Level

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03013114
• Other study ID #: ITP-Bortezomib
• Status: Not yet recruiting
• Phase: Phase 2
• First received: December 22, 2016
• Last updated: January 5, 2017
• Start date: January 2017
• Est. completion date: December 2017

Study information

• Verified date: January 2017
• Source: Shandong University
• Contact: Ming Hou
• Email: houming[@]medmail.com.cn
• Is FDA regulated: No
• Health authority: China: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

Primary immune thrombocytopenia (ITP) is a disorder caused by autoantibody-mediated platelet destruction and decreased platelet production. It has been reported that refractory ITP is closely related to long-lived plasma cells (PCs), which are resistant to glucocorticoids, conventional immunosuppressive and cytotoxic drugs, irradiation and B-cell depletion therapies.

Proteasome inhibition bortezomib is one of the most promising therapeutic approaches to target PCs, since this strategy has been shown to efficiently eliminate multiple myeloma cells, that is, transformed PCs. It also has been successfully used in SLE-like mice, experimental autoimmune MG rats and experimental hemophilia-A mice that develop anti-factor VIII antibodies in preclinical models by depleting both short-lived and long-lived PCs. Additionally, treatment with bortezomib resulted in a rapid clinical response in a patient with refractory thrombotic thrombocytopenic purpura associated with the depletion of inhibitory autoantibodies against ADAMTS13, a metalloproteinase that cleaves the von Wille-brand factor, which is produced by plasma cells. Hence, the elimination of autoreactive PCs by proteasome inhibitors might represent a new treatment strategy for autoantibody-mediated diseases.

To date, refractory ITP is lacking of effective treatments and these findings encouraged us to conduct a study of bortezomib in management of ITP with high anti-platelet antibodies level. Data from this study may provide some idea of bortezomib in the treatment of ITP.

Description:

The investigators are undertaking a single-center, single-arm study of 20 primary ITP adult patients from Shandong University Qilu Hospital

. All the participants are selected to receive bortezomib treatment (given intravenously at a dose of 1.3mg/m2 on days 1,4,8,11). Platelet count, bleeding and other symptoms were evaluated before and after treatment. Adverse events are also recorded throughout the study.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: December 2017
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• failure to achieve at least Response

• need of treatment(s) (including, but not limited to, low dose of corticosteroids) to minimize the risk of clinically significant bleeding. Need of on-demand or adjunctive therapy alone does not qualify the patient as refractory

• 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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Immune Thrombocytopenia
• Purpura, Thrombocytopenic, Idiopathic
• Thrombocytopenia

Intervention

Drug:
• Bortezomib
Bortezomib was given by intravenous bolus injection at a dose of 1.3 mg/m2 on days 1, 4, 8 and 11, repeated every 21 days. It will be given four cycles.

Locations

Country	Name	City	State
China	Shandong University Qilu hospital	Jinan	Shandong

Sponsors (1)

Lead Sponsor	Collaborator
Shandong University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Platelet counts	Complete response (CR): A platelet count = 100 * 10^9/L measured on two occasions > 7 days apart and the absence of bleeding.; Response (R): A platelet count = 30 * 10^9/L and a greater than two fold increase in platelet count from baseline measured on two occasions > 7 days apart and the absence of bleeding.; No response (NR): A platelet count < 30 * 10^9/L or a less than two fold increase in platelet count from baseline or the presence of bleeding. Platelet count must be measured on two occasions more than a day apart.	an average of 3 months	Yes
Secondary	Numbers of Megakaryocyte Polyploidy		6 days after every treatment cycle, an average of 3 months	Yes
Secondary	Expression rate of long-lived plasma cells		6 days after every treatment cycle, an average of 3 months	Yes