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

An Open-label Phase II Study to Determine the Efficacy and Safety of Rituximab and Bortezomib in Patients With Newly Diagnosed Acquired Hemophilia A

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.

Study Overview

• Status: Unknown
• Conditions: Acquired Hemophilia A
• Intervention / Treatment: Drug: Bortezomib; Drug: Rituximab

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.

• Study Type: Interventional
• Enrollment (Anticipated): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Peking Union Medical College Hospital
      • Contact: Huacong Cai; Phone Number: 01069158271; Email: caihc@pumch.cn
      • Contact: Tienan Zhu, MD; Phone Number: 01069158271; Email: zhutn@pumch.cn
      • Principal Investigator: Tienan Zhu, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Bortezomib +Rituximab	Drug: Bortezomib; Bortezomib intravenously 1.3mg/m2 d1,4,8,11 for 4 doses; Drug: Rituximab; rituximab intravenously 500 mg for one dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Adverse events	Include major bleeding, infection, nerve toxicity, and so on.	During 24 month
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

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Investigators: Principal Investigator: Tienan Zhu, Peking Union Medical College Hospital

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 10, 2018
• Primary Completion (ANTICIPATED): October 15, 2019
• Study Completion (ANTICIPATED): April 15, 2020

Study Registration Dates

• First Submitted: October 4, 2018
• First Submitted That Met QC Criteria: October 6, 2018
• First Posted (ACTUAL): October 9, 2018

Study Record Updates

• Last Update Posted (ACTUAL): November 23, 2018
• Last Update Submitted That Met QC Criteria: November 20, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab; Bortezomib
• Other Study ID Numbers: PUMCH-AHA-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No