Study to Evaluate Rituximab and Bortezomib in Patients With Newly Diagnosed Acquired Hemophilia A

Acquired Hemophilia A Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03700229
• Other study ID #: PUMCH-AHA-001
• Status: Recruiting
• Phase: Phase 2
• Start date: October 10, 2018
• Est. completion date: April 15, 2020

Study information

• Verified date: November 2018
• Source: Peking Union Medical College Hospital
• Contact: Huacong Cai
• Phone: 01069158271
• Email: caihc[@]pumch.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 22
• Est. completion date: April 15, 2020
• Est. primary completion date: October 15, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acquired Hemophilia A
• Hemophilia A

Intervention

Drug:
• Bortezomib
Bortezomib intravenously 1.3mg/m2 d1,4,8,11 for 4 doses
• Rituximab
rituximab intravenously 500 mg for one dose

Locations

Country	Name	City	State
China	Peking Union Medical College Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital

Country where clinical trial is conducted

China, 

References & Publications (4)

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. Review. — View Citation

Brás GP, Pinto RJ, Carvalho MM, Fernandes SP, Andrade JJ, Guimarães 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. — View Citation

Collins P, Baudo F, Knoebl P, Lévesque H, Nemes L, Pellegrini F, Marco P, Tengborn L, Huth-Kühne 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. — View 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) — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The time to attain first complete remission (CR)	Complete remission defined as titer FVIII inhibitor lower than 0.6 Bethesda unit, factor VIII level> 50% and no bleeding events without bypass treatments for 24 hours	Last day of the treatment regimen (up to 3 months)
Secondary	The time to durable treatment response	The time to durable treatment response was defined as the time from date of achieving CR until the date of relapse or date of death from any cause(whichever came first)	During 24 month
Secondary	Adverse events	Include major bleeding, infection, nerve toxicity, and so on.	During 24 month
Secondary	Overall survival	Overall survival was defined as the time from date of first diagnosis until the date of death from any cause,and death from any cause will be recorded.	During 24 month