Efficacy and Safety of Bortezomib as First-line Treatment of Acquired TTP

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of bortezomib in the first-line treatment of patients with acquired TTP，we design this prospective, multi-center, single-arm interventional study.All enrolled TTP patients were given bortezomib 1.3 mg/m2 intravenous injection d1, 4, 8, on the basis of standard single membrane plasma exchange (2L/d) and hormone therapy (1mg/kg prednisone or equivalent methylprednisolone). 11 (4 doses in total). Bortezomib should be administered immediately after each plasma exchange, and the interval between the next plasma exchange is> 24h. Plasma exchange continued until the patient's platelet count was >100×109/L for 2 consecutive days, and then changed to once every other day for a total of two times and then stopped.

Detailed Description
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To evaluate the efficacy and safety of bortezomib in the first-line treatment of patients with acquired TTP，we design this prospective, multi-center, single-arm interventional study.All enrolled TTP patients were given bortezomib 1.3 mg/m2 intravenous injection d1, 4, 8, on the basis of standard single membrane plasma exchange (2L/d) and hormone therapy (1mg/kg prednisone or equivalent methylprednisolone). 11 (4 doses in total). Bortezomib should be administered immediately after each plasma exchange, and the interval between the next plasma exchange is> 24h. Plasma exchange continued until the patient's platelet count was >100×109/L for 2 consecutive days, and then changed to once every other day for a total of two times and then stopped.

Official Title
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The Efficacy and Safety of Bortezomib as First-line Treatment for Acquired Thrombotic Thrombocytopenic Purpura

Conditions
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Thrombotic Thrombocytopenic Purpura, Acquired

Intervention / Treatment
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* Drug: Bortezomib Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: clinically diagnosed as TTP (thrombocytopenia + MAHA± clinical evidence of related organ damage， a significant reduction in ADAMTS13 activity level and/or positive antibody screening） elder than 18 years old; informed consent is required; Exclusion Criteria: Uncontrollable systemic infection; Known allergy to bortezomib; Expected survival time <1 week; Pregnant or lactating women (women of childbearing age have a positive pregnancy test at baseline or have not received a pregnancy test. Postmenopausal women must be at least 12 months after menopause); If the creatinine level is ≥200μmol/l (1.5mg/dl), the levels of transaminase and bilirubin are 2 times higher than the upper limit of normal (except due to the primary disease); Known congenital TTP or a clear family history of TTP; Other diseases that cause microangiopathic hemolysis and thrombocytopenia, such as DIC, APS, HUS, malignant hypertension, transplantation-related microangiopathy; active malignant tumors (except skin basal cell carcinoma or cervical carcinoma in situ) ( have not been treated or recurred within 5 years before signing the informed consent); peripheral neuropathy; Patients or family members cannot understand the conditions and goals of this study; The investigator believes that the patient should not participate in any other situations in this trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Interventional Model Description: Clinically diagnosed as TTP (thrombocytopenia + MAHA± clinical evidence of related organ damage), confirmed by ADAMTS13 activity level decreased significantly and/or positive antibody screening
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: bortezomib group<br>On the basis of standard single membrane plasma exchange (2L/d) and hormone therapy (1mg/kg prednisone or equivalent methylprednisolone), bortezomib was given intravenous injection of 1.3mg/m2 d1, 4, 8, 11 (total 4 doses). | Drug: Bortezomib Injection<br>* Bortezomib should be administered immediately after each plasma exchange, and the interval between the next plasma exchange is> 24h. Plasma exchange continued until the patient's platelet count was >100×109/L for 2 consecutive days, and then changed to once every other day for a total of two times and then stopped.<br>* Other names: hormone therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to clinical remission and the number of plasma exchanges required | clinical remission means clinical symptom remission and/or adamts13 antibody negative，time to clinical remission means the days from first plasma exchange to clinical remission. the number of plasma exchanges required means the whole number of plasma exchanges in this course of TTP. | one month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality rate | The ratio of the number of deaths to the total number of cases | 6 months | 
| ICU hospitalization time and total hospitalization time; | ICU hospitalization time means Duration of treatment in the ICU during the course of the disease(the number of days), total time in hospital(the number of days) | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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thrombotic thrombocytopenic purpura, bortezomib, plasma exchange