Trial of Acquired Haemophilia With Steroid Combined With Cyclophosphamide Versus Steroid Combined With Rituximab

June 14, 2023 updated by: Zhang Lei, MD

A Prospective, Randomized, Multicenter Clinical Trial of Acquired Haemophilia A With Steroid Combined With Cyclophosphamide Versus Steroid Combined With Rituximab

Purpose:

To evaluate the efficacy when administering steroid combined with single dose rituximab to eliminate the antibody in acquired hemophilia A patients compared to treatment using steroid with cyclophosphamide.

The study will test the hypothesis that steroid combined with small dose rituximab is as effective as steroid combined with cyclophosphamide for FVIII inhibitor eradication in Chinese patients with acquired hemophilia A.

Study design Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a prospective randomized multi-center controlled pilot trial comparing the regimen of steroid with rituximab and steroid with cyclophosphamide to eradicate anti-factor VIII antibodies in Chinese patients with acquired hemophilia A.

Patients will be randomized to two regimens: methylprednisolone 0.8mg/kg/day (or equivalent corticosteroid doses) for 3 weeks (then tapering gradually,8 weeks in total) with rituximab (375mg/m2 for one dose) or methylprednisolone 0.8mg/kg/day (or equivalent corticosteroid doses) for 3 weeks (then tapering gradually,8 weeks in total) with cyclophosphamide 2mg/kg/day until inhibitor negative(no longer than five weeks).

Patients will be randomized to the treatment cohorts according to the biostatistical methods.

Study Type

Interventional

Enrollment (Actual)

66

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Tianjin
      • Tianjin, Tianjin, China, 300020
        • Ethics Committee of Blood disease hospital, Chinese Academy of Medical Sciences

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 18-80 years old
  • Men or women
  • Women post-menopausal or with ongoing contraception
  • Diagnosis of acquired hemophilia A
  • Patient must be insured
  • Patient has provided written informed consent prior to enrollment
  • Patient compliant

Exclusion Criteria:

  • Congenital hemophilia
  • Ongoing treatment with prednisone > 20mg/d （or equivalent corticosteroid doses） more than 1 month
  • Ongoing treatment with prednisone >0.7mg/kg（or equivalent corticosteroid doses） more than 10 days
  • Pregnant and breastfeeding women
  • Allergy to steroid
  • Immunosuppressive agents treatment within 30 days
  • Serum transaminase and bilirubin greater than 1.5 times the upper limit of normal value
  • Hepatitis B surface antigen or hepatitis C antibody or HIV antibody (I + II) or syphilis antibody positive
  • Patients with diabetes, hypertension, glaucoma, peptic ulcer, herpes zoster, pulmonary infection and so on, who should not be treated with glucocorticoids
  • Patients with poor compliance
  • Those who can not take contraceptive measures during the test period
  • Patient who is considered by the investigator not suitable for clinical study
  • Thrombocytopenia
  • Leucocytopenia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Steroid+Rituximab
Methylprednisolone 0.8 mg/kg/day (or equivalent corticosteroid doses) for 3 weeks（then tapering gradually, 8 weeks in total）+Rituximab 375mg/m2 for one dose.
Drug: Steroid
Methylprednisolone 0.8 mg/kg/day (or equivalent corticosteroid doses) for 3 weeks（then tapering gradually, 8 weeks in total）
Other Names:
  • Corticosteroid
Drug: Rituximab
375mg/m2 for one dose
Active Comparator: Steroid +Cyclophosphamide
Methylprednisolone 0.8 mg/kg/day (or equivalent corticosteroid doses) for 3 weeks （ then tapering gradually, 8 weeks in total）+ Cyclophosphamide 2 mg/kg/day until inhibitor negative (no longer than five weeks)
Drug: Steroid
Methylprednisolone 0.8 mg/kg/day (or equivalent corticosteroid doses) for 3 weeks（then tapering gradually, 8 weeks in total）
Other Names:
  • Corticosteroid
Drug: Cyclophosphamide
cyclophosphamide 2 mg/kg/day until inhibitor negative (no longer than five weeks)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of inhibitor eradication and time to attain first remission
Time Frame: During 18 months
The proportion of patients achieving complete remission (CR) 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 and the time to attain first remission will be evaluated.
During 18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relapse rate and time to relapse
Time Frame: During 18 month
The proportion of patients who relapse and the time to relapse of each regimen will be measured.
During 18 month

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Infection of two regimens
Time Frame: During 18 months
The safety outcomes will be the occurrence of infection related to immunosuppressive treatment adverse events.
During 18 months
Hemocytopenia of two regimens
Time Frame: During 18 month
The safety outcomes will be the occurrence of Hemocytopenia related to immunosuppressive treatment adverse events.
During 18 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Zhang Lei, MD

Collaborators

Henan Cancer Hospital
Qilu Hospital of Shandong University
Tianjin First Central Hospital
The Second Affiliated Hospital of Kunming Medical University

Investigators

  • Principal Investigator: Lei Zhang, MD, Blood Disease Hospital, Chinese Academy of Medical Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 29, 2017

Primary Completion (Actual)

June 9, 2022

Study Completion (Actual)

July 9, 2022

Study Registration Dates

First Submitted

November 28, 2017

First Submitted That Met QC Criteria

December 24, 2017

First Posted (Actual)

December 27, 2017

Study Record Updates

Last Update Posted (Actual)

June 15, 2023

Last Update Submitted That Met QC Criteria

June 14, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IHBDH-IIT2017006

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified individual participant data for all primary and secondary outcome will be made available

IPD Sharing Time Frame

Data will be available within 6 month of study completion

IPD Sharing Access Criteria

Data access requests will be reviewed by an external independent Review Panel. Requests will be required to sign a Data Access Agreement

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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