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

Sponsor

Peking Union Medical College Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05135442

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Thrombotic Thrombocytopenic Purpura, Acquired	Drug: Bortezomib Injection	Phase 4

Detailed Description

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention 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 screeningClinically 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)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Dec 1, 2021

Anticipated Primary Completion Date :

Nov 30, 2023

Anticipated Study Completion Date :

Nov 30, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: bortezomib group 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 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. Other Names: plasma exchange hormone therapy

Arm

Intervention/Treatment

Experimental: bortezomib group

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

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.

Other Names:

plasma exchange

hormone therapy

Outcome Measures

Primary Outcome Measures

Time to clinical remission and the number of plasma exchanges required [one month]
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.

Secondary Outcome Measures

Mortality rate [6 months]
The ratio of the number of deaths to the total number of cases
ICU hospitalization time and total hospitalization time; [6 months]
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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.