Clinical trial NCT05135442: 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
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Thrombotic Thrombocytopenic Purpura, Acquired
Keywords: thrombotic thrombocytopenic purpura
bortezomib
plasma exchange
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2021-11-26
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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 screening
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Time to clinical remission and the number of plasma exchanges required
timeFrame: one month
Secondary outcomes:
measure: Mortality rate
timeFrame: 6 months
measure: ICU hospitalization time and total hospitalization time;
timeFrame: 6 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: (Select)
Study officials:
affiliation: Peking Union Medical College Hospital
name: tienan zhu
role: STUDY_CHAIR
References:
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.
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.
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.