Clinical trial NCT03700229: Study to Evaluate Rituximab and Bortezomib in Patients With Newly Diagnosed Acquired Hemophilia A
Official title: An Open-label Phase II Study to Determine the Efficacy and Safety of Rituximab and Bortezomib in Patients With Newly Diagnosed Acquired Hemophilia A
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Acquired Hemophilia A
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2018-10-09
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this prospective study is to determine the efficacy and safety of Rituximab plus Bortezomib in patients with newly diagnosed acquired hemophilia A.

Detailed description: This is a prospective, single-arm, open-label clinical trial to evaluate the efficacy and safety the regimen of Bortezomib with rituximab as first-line treatment to eradicate anti-factor VIII antibodies in newly diagnosed acquired hemophilia A.

All of enrolled patients in this study will be injected Bortezomib plus rituximab. This study will be performed for about 2 years and approximately 22 patients will be enrolled in our insititution.

After obtaining the written informed consent from the patients, the information of demographic and medical history will be collected and laboratory tests will be performed.

Patients who meet the inclusion/exclusion criteria will be received the regimens: Bortezomib (1.3mg/m2 d1,4,8,11) with rituximab (375mg/m2 for one dose). The information of adverse events will be collected. In case that the evaluation of treatment response might be performed in regular clinical practice, those data will also be collected as well.

Eligibility criteria: Inclusion Criteria:

1. Must be ≥ 18 years;
2. Understand and voluntarily sign an ICD prior to any study related assessments/procedures are conducted;
3. Diagnosis of acquired hemophilia A；
4. acute bleeding episodes(≥once).

Exclusion Criteria:

1. Uncontrolled systemic infection;
2. Allergy to rituximab;
3. Positive for Lupus anticoagulant;
4. Life expectancy \< 3 months;
5. Pregnant and breastfeeding women;
6. Neuropathy\>Grade 1;
7. Positive for Hepatitis B surface antigen or hepatitis C antibody or human immunodeficiency virus（HIV）antibody;
8. Patients with poor compliance；
9. Patient who is considered by the investigator not suitable for clinical study.

Primary outcomes:
measure: The time to attain first complete remission (CR)
timeFrame: Last day of the treatment regimen (up to 3 months)
Secondary outcomes:
measure: The time to durable treatment response
timeFrame: During 24 month
measure: Adverse events
timeFrame: During 24 month
measure: Overall survival
timeFrame: During 24 month
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
affiliation: Peking Union Medical College Hospital
name: Tienan Zhu
role: PRINCIPAL_INVESTIGATOR
References:
citation: Collins P, Baudo F, Knoebl P, Levesque H, Nemes L, Pellegrini F, Marco P, Tengborn L, Huth-Kuhne A; EACH2 registry collaborators. Immunosuppression for acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2). Blood. 2012 Jul 5;120(1):47-55. doi: 10.1182/blood-2012-02-409185. Epub 2012 Apr 18.
citation: Bras GP, Pinto RJ, Carvalho MM, Fernandes SP, Andrade JJ, Guimaraes JE. Bortezomib: Potential Key Role in the Treatment of Multiple Myeloma-Related Acquired Hemophilia A. Semin Thromb Hemost. 2017 Feb;43(1):109-112. doi: 10.1055/s-0036-1597648. Epub 2016 Dec 19. No abstract available.
citation: Bonfanti C, Crestani S, Frattini F, Sissa C, Franchini M. Role of rituximab in the treatment of postpartum acquired haemophilia A: a systematic review of the literature. Blood Transfus. 2015 Jul;13(3):396-400. doi: 10.2450/2014.0242-14. Epub 2014 Dec 17. No abstract available.
citation: Ratnasingam S, Walker PA, Tran H, Kaplan ZS, McFadyen JD, Tran H, Teh TC, Fleming S, Catalano JV, Chunilal SD, Johnston A, Opat SS, Shortt J. Bortezomib-based antibody depletion for refractory autoimmune hematological diseases. Blood Adv. 2016 Nov 22;1(1):31-35. doi: 10.1182/bloodadvances.2016001412. eCollection 2016 Nov 29.