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

NCT05135442 | Unknown Phase 4

• 1 other identifier: FTTPB
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Thrombotic Thrombocytopenic Purpura, Acquired

Keywords

thrombotic thrombocytopenic purpura; bortezomib; plasma exchange

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Mortality rate

  6 months

• ICU hospitalization time and total hospitalization time;

  6 months

Study Arms (1)

bortezomib group

EXPERIMENTAL

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

Interventions

Bortezomib Injection DRUG

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.

Also known as: plasma exchange, hormone therapy

bortezomib group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, (Select), 100730, China

Location

Related Publications (3)

• 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.

  PMID: 27868334 BACKGROUND

• 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.

  PMID: 27009919 BACKGROUND

• 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.

  PMID: 23281998 BACKGROUND

MeSH Terms

Conditions

Thrombotic thrombocytopenic purpura, acquired; Purpura, Thrombotic Thrombocytopenic

Interventions

Bortezomib; Plasma Exchange

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Thrombophilia; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Blood Transfusion; Biological Therapy; Therapeutics; Plasmapheresis; Blood Component Removal; Sorption Detoxification; Extracorporeal Circulation; Surgical Procedures, Operative

Study Officials

• tienan zhu

  Peking Union Medical College Hospital

  STUDY CHAIR

Central Study Contacts

jing yang

CONTACT

1069159146; yangbujing@126.com

huacong cai

CONTACT

caihc@pumch.cn

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Clinically diagnosed as TTP (thrombocytopenia + MAHA± clinical evidence of related organ damage), confirmed by ADAMTS13 activity level decreased significantly and/or positive antibody screening

Study Record Dates

• First Submitted: November 6, 2021
• First Posted: November 26, 2021
• Study Start: December 1, 2021
• Primary Completion: November 30, 2023
• Study Completion: November 30, 2025
• Last Updated: November 26, 2021

Record last verified: 2021-11

Locations

CN (1)