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

Primary Purpose

Thrombotic Thrombocytopenic Purpura, Acquired

Status
Not yet recruiting
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Bortezomib Injection
Sponsored by
Peking Union Medical College Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Thrombotic Thrombocytopenic Purpura, Acquired focused on measuring thrombotic thrombocytopenic purpura, bortezomib, plasma exchange

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Peking Union Medical College Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

bortezomib group

Arm Description

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Mortality rate
The ratio of the number of deaths to the total number of cases
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)

Full Information

First Posted
November 6, 2021
Last Updated
November 22, 2021
Sponsor
Peking Union Medical College Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05135442
Brief Title
Efficacy and Safety of Bortezomib as First-line Treatment of Acquired TTP
Official Title
The Efficacy and Safety of Bortezomib as First-line Treatment for Acquired Thrombotic Thrombocytopenic Purpura
Study Type
Interventional

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Not yet recruiting
Study Start Date
December 1, 2021 (Anticipated)
Primary Completion Date
November 30, 2023 (Anticipated)
Study Completion Date
November 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Peking Union Medical College Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. 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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Thrombotic Thrombocytopenic Purpura, Acquired
Keywords
thrombotic thrombocytopenic purpura, bortezomib, plasma exchange

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
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)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
bortezomib group
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Bortezomib Injection
Other Intervention Name(s)
plasma exchange, hormone therapy
Intervention Description
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.
Primary Outcome Measure Information:
Title
Time to clinical remission and the number of plasma exchanges required
Description
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.
Time Frame
one month
Secondary Outcome Measure Information:
Title
Mortality rate
Description
The ratio of the number of deaths to the total number of cases
Time Frame
6 months
Title
ICU hospitalization time and total hospitalization time;
Description
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)
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
jing yang
Phone
1069159146
Email
yangbujing@126.com
First Name & Middle Initial & Last Name or Official Title & Degree
huacong cai
Email
caihc@pumch.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
tienan zhu
Organizational Affiliation
Peking Union Medical College Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Peking Union Medical College Hospital
City
Beijing
State/Province
(Select)
ZIP/Postal Code
100730
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
jing yang
Phone
106915914
Email
yangbujing@126.com

12. IPD Sharing Statement

Citations:
PubMed Identifier
27868334
Citation
Scully M, Cataland S, Coppo P, de la Rubia J, Friedman KD, Kremer Hovinga J, Lammle B, Matsumoto M, Pavenski K, Sadler E, Sarode R, Wu H; International Working Group for Thrombotic Thrombocytopenic Purpura. Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies. J Thromb Haemost. 2017 Feb;15(2):312-322. doi: 10.1111/jth.13571. Epub 2017 Jan 30.
Results Reference
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PubMed Identifier
27009919
Citation
Patriquin CJ, Thomas MR, Dutt T, McGuckin S, Blombery PA, Cranfield T, Westwood JP, Scully M. Bortezomib in the treatment of refractory thrombotic thrombocytopenic purpura. Br J Haematol. 2016 Jun;173(5):779-85. doi: 10.1111/bjh.13993. Epub 2016 Mar 24.
Results Reference
background
PubMed Identifier
23281998
Citation
Shortt J, Oh DH, Opat SS. ADAMTS13 antibody depletion by bortezomib in thrombotic thrombocytopenic purpura. N Engl J Med. 2013 Jan 3;368(1):90-2. doi: 10.1056/NEJMc1213206. No abstract available.
Results Reference
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Efficacy and Safety of Bortezomib as First-line Treatment of Acquired TTP

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