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

NCT03013114 | Unknown Phase 2 DMC

• 1 other identifier: ITP-Bortezomib
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Immune Thrombocytopenia

Keywords

Bortezomib Immune thrombocytopenia

Outcome Measures

Primary Outcomes (1)

• Platelet counts

  1. Complete response (CR)： A platelet count ≥ 100 \* 10\^9/L measured on two occasions \> 7 days apart and the absence of bleeding. 2. 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. 3. 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

Secondary Outcomes (2)

• Numbers of Megakaryocyte Polyploidy

  6 days after every treatment cycle, an average of 3 months

• Expression rate of long-lived plasma cells

  6 days after every treatment cycle, an average of 3 months

Study Arms (1)

Bortezomib

EXPERIMENTAL

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.

Drug: Bortezomib

Interventions

Bortezomib DRUG

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.

Bortezomib

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• pregnancy
• hypertension
• cardiovascular disease
• diabetes
• liver and kidney function impairment
• HCV, HIV, HBsAg seropositive status
• patients with systemic lupus erythematosus and/or antiphospholipid syndrome

Sponsors & Collaborators

• Shandong University: lead

Study Sites (1)

Shandong University Qilu hospital

Jinan, Shandong, 250012, China

Location

MeSH Terms

Conditions

Purpura, Thrombocytopenic, Idiopathic

Interventions

Bortezomib

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Ming Hou

  Qilu Hospital of Shandong University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ming Hou

CONTACT

houming@medmail.com.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Director

Study Record Dates

• First Submitted: December 22, 2016
• First Posted: January 6, 2017
• Study Start: January 1, 2017
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: January 6, 2017

Record last verified: 2017-01

Locations

CN (1)