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出境医 / 临床实验 / Study to Evaluate Rituximab and Bortezomib in Patients With Newly Diagnosed Acquired Hemophilia A

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

Study Description
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.

Condition or disease Intervention/treatment Phase
Acquired Hemophilia A Drug: Bortezomib Drug: Rituximab Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 22 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 10, 2018
Estimated Primary Completion Date : October 15, 2019
Estimated Study Completion Date : April 15, 2020
Arms and Interventions
Arm Intervention/treatment
Experimental: Bortezomib +Rituximab
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

Outcome Measures
Primary Outcome Measures :
  1. The time to attain first complete remission (CR) [ Time Frame: Last day of the treatment regimen (up to 3 months) ]
    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


Secondary Outcome Measures :
  1. The time to durable treatment response [ Time Frame: During 24 month ]
    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)

  2. Adverse events [ Time Frame: During 24 month ]
    Include major bleeding, infection, nerve toxicity, and so on.

  3. Overall survival [ Time Frame: During 24 month ]
    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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations

Contacts
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Contact: Huacong Cai 01069158271 caihc@pumch.cn
Contact: Tienan Zhu 01069158271 zhutn@pumch.cn

Locations
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China, Beijing
Peking Union Medical College Hospital Recruiting
Beijing, Beijing, China, 100730
Contact: Huacong Cai    01069158271    caihc@pumch.cn   
Contact: Tienan Zhu, MD    01069158271    zhutn@pumch.cn   
Principal Investigator: Tienan Zhu, MD         
Sponsors and Collaborators
Peking Union Medical College Hospital
Investigators
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Principal Investigator: Tienan Zhu Peking Union Medical College Hospital
Tracking Information
First Submitted Date  ICMJE October 4, 2018
First Posted Date  ICMJE October 9, 2018
Last Update Posted Date November 23, 2018
Actual Study Start Date  ICMJE October 10, 2018
Estimated Primary Completion Date October 15, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 6, 2018)
The time to attain first complete remission (CR) [ Time Frame: Last day of the treatment regimen (up to 3 months) ]
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 6, 2018)
  • The time to durable treatment response [ Time Frame: During 24 month ]
    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)
  • Adverse events [ Time Frame: During 24 month ]
    Include major bleeding, infection, nerve toxicity, and so on.
  • Overall survival [ Time Frame: During 24 month ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Evaluate Rituximab and Bortezomib in Patients With Newly Diagnosed Acquired Hemophilia A
Official Title  ICMJE An Open-label Phase II Study to Determine the Efficacy and Safety of Rituximab and Bortezomib in Patients With Newly Diagnosed Acquired Hemophilia A
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acquired Hemophilia A
Intervention  ICMJE
  • Drug: Bortezomib
    Bortezomib intravenously 1.3mg/m2 d1,4,8,11 for 4 doses
  • Drug: Rituximab
    rituximab intravenously 500 mg for one dose
Study Arms  ICMJE Experimental: Bortezomib +Rituximab
Bortezomib +Rituximab
Interventions:
  • Drug: Bortezomib
  • Drug: Rituximab
Publications *
  • 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.
  • 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.
  • 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.
  • 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: October 6, 2018)
22
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 15, 2020
Estimated Primary Completion Date October 15, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03700229
Other Study ID Numbers  ICMJE PUMCH-AHA-001
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Tienan Zhu, Peking Union Medical College Hospital
Study Sponsor  ICMJE Peking Union Medical College Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Tienan Zhu Peking Union Medical College Hospital
PRS Account Peking Union Medical College Hospital
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP