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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Acquired Hemophilia A

Intervention / Treatment
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* Drug: Steroid
* Drug: Rituximab
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of inhibitor eradication and time to attain first remission | 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 | The proportion of patients who relapse and the time to relapse of each regimen will be measured. | During 18 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acquired hemophilia A, Cyclophosphamide, Rituximab, Steroid