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

Thrombotic Thrombocytopenic Purpura, Acquired Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05135442
• Other study ID #: FTTPB
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: December 1, 2021
• Est. completion date: November 30, 2025

Study information

• Verified date: November 2021
• Source: Peking Union Medical College Hospital
• Contact: jing yang
• Phone: 1069159146
• Email: yangbujing[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: November 30, 2025
• Est. primary completion date: November 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Purpura
• Purpura, Thrombocytopenic
• Purpura, Thrombotic Thrombocytopenic
• Thrombotic Thrombocytopenic Purpura, Acquired

Intervention

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.

Locations

Country	Name	City	State
China	Peking Union Medical College Hospital	Beijing	(Select)

Sponsors (1)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital

Country where clinical trial is conducted

China, 

References & Publications (3)

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. — View Citation

Scully M, Cataland S, Coppo P, de la Rubia J, Friedman KD, Kremer Hovinga J, Lämmle 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Mortality rate	The ratio of the number of deaths to the total number of cases	6 months
Secondary	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