Clinical trial NCT03013114: A Single-center Clinical Trial of Bortezomib in Management of Immune Thrombocytopenia (ITP)
Official title: A Single-center Clinical Trial of Bortezomib in Management of Immune Thrombocytopenia (ITP) With High Anti-platelet Antibodies Level
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Immune Thrombocytopenia
Keywords: Bortezomib Immune thrombocytopenia
Lead sponsor: Shandong University
Sponsor class: OTHER
First posted: 2017-01-06
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Platelet counts
timeFrame: an average of 3 months
Secondary outcomes:
measure: Numbers of Megakaryocyte Polyploidy
timeFrame: 6 days after every treatment cycle, an average of 3 months
measure: Expression rate of long-lived plasma cells
timeFrame: 6 days after every treatment cycle, an average of 3 months
Other outcomes:
Locations:
city: Jinan
country: China
facility: Shandong University Qilu hospital
state: Shandong
Study officials:
affiliation: Qilu Hospital, Shandong University
name: Ming Hou
role: PRINCIPAL_INVESTIGATOR
References: