Study to Evaluate Rituximab and Bortezomib in Patients With Newly Diagnosed Acquired Hemophilia A

Study Overview
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Brief Summary
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The purpose of this prospective study is to determine the efficacy and safety of Rituximab plus Bortezomib in patients with newly diagnosed acquired hemophilia A.

Detailed Description
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This is a prospective, single-arm, open-label clinical trial to evaluate the efficacy and safety the regimen of Bortezomib with rituximab as first-line treatment to eradicate anti-factor VIII antibodies in newly diagnosed acquired hemophilia A. All of enrolled patients in this study will be injected Bortezomib plus rituximab. This study will be performed for about 2 years and approximately 22 patients will be enrolled in our insititution. After obtaining the written informed consent from the patients, the information of demographic and medical history will be collected and laboratory tests will be performed. Patients who meet the inclusion/exclusion criteria will be received the regimens: Bortezomib (1.3mg/m2 d1,4,8,11) with rituximab (375mg/m2 for one dose). The information of adverse events will be collected. In case that the evaluation of treatment response might be performed in regular clinical practice, those data will also be collected as well.

Official Title
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An Open-label Phase II Study to Determine the Efficacy and Safety of Rituximab and Bortezomib in Patients With Newly Diagnosed Acquired Hemophilia A

Conditions
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Acquired Hemophilia A

Intervention / Treatment
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* Drug: Bortezomib
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be ≥ 18 years; Understand and voluntarily sign an ICD prior to any study related assessments/procedures are conducted; Diagnosis of acquired hemophilia A； acute bleeding episodes(≥once). Exclusion Criteria: Uncontrolled systemic infection; Allergy to rituximab; Positive for Lupus anticoagulant; Life expectancy < 3 months; Pregnant and breastfeeding women; Neuropathy>Grade 1; Positive for Hepatitis B surface antigen or hepatitis C antibody or human immunodeficiency virus（HIV）antibody; Patients with poor compliance； Patient who is considered by the investigator not suitable for clinical study.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bortezomib +Rituximab<br>Bortezomib +Rituximab | Drug: Bortezomib<br>* Bortezomib intravenously 1.3mg/m2 d1,4,8,11 for 4 doses<br>Drug: Rituximab<br>* rituximab intravenously 500 mg for one dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The time to attain first complete remission (CR) | Complete remission defined as titer FVIII inhibitor lower than 0.6 Bethesda unit, factor VIII level> 50% and no bleeding events without bypass treatments for 24 hours | Last day of the treatment regimen (up to 3 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The time to durable treatment response | The time to durable treatment response was defined as the time from date of achieving CR until the date of relapse or date of death from any cause（whichever came first） | During 24 month | 
| Adverse events | Include major bleeding, infection, nerve toxicity, and so on. | During 24 month | 
| Overall survival | Overall survival was defined as the time from date of first diagnosis until the date of death from any cause，and death from any cause will be recorded. | During 24 month |