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

Phase 4

Completed

• Conditions: Acquired Hemophilia A
• Interventions: Drug: Steroid; Drug: Cyclophosphamide; Drug: Rituximab

• Registration Number: NCT03384277
• Lead Sponsor: Zhang Lei, MD

Brief Summary

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

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2017-11-28
• Study First Submitted QC: 2017-12-24
• Study First Posted: 2017-12-27
• Study Start: 2017-12-29
• Primary Completion: 2022-06-09
• Study Completion: 2022-07-09
• Status Verified: 2023-06
• Last Update Submitted: 2023-06-14
• Last Update Posted: 2023-06-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 66

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Steroid +Cyclophosphamide	Steroid	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)
Steroid +Cyclophosphamide	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)
Steroid+Rituximab	Steroid	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.
Steroid+Rituximab	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.

Primary Outcome Measures

Name	Time	Method
Proportion of inhibitor eradication and time to attain first remission	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.

Secondary Outcome Measures

Name	Time	Method
Relapse rate and time to relapse	During 18 month	The proportion of patients who relapse and the time to relapse of each regimen will be measured.

Trial Locations

Locations (1)

Ethics Committee of Blood disease hospital, Chinese Academy of Medical Sciences; 🇨🇳 Tianjin, Tianjin, China