Outcome of Acquired Haemophilia With Steroid Combined With Cyclophosphamide Versus Steroid Combined With Rituximab (CREHA Study)

Study Overview
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Brief Summary
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CREHA project is a study comparing steroid combined with cyclophosphamide versus steroid combined with rituximab in patients with acquired haemophilia. The study will test the hypothesis that steroid combined with cyclophosphamide is more effective than steroid plus rituximab for FVIII inhibitor eradication in acquired haemophilia.

Detailed Description
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CREHA project is a multicenter, randomized, controlled efficacity and safety study comparing steroid combined with cyclophosphamide versus steroid combined with rituximab in patients with acquired haemophilia. The study will test the hypothesis that steroid combined with cyclophosphamide is more effective than steroid plus rituximab for FVIII inhibitor eradication in acquired haemophilia

Official Title
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Outcome of Acquired Haemophilia With Steroid Combined With Cyclophosphamide Versus Steroid Combined With Rituximab (CREHA Study)

Conditions
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Acquired Haemophilia

Intervention / Treatment
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* Drug: Steroid + cyclophosphamide
* Drug: Steroid + rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: men or women women post-menpausal or with ongoing contraception 18 years old or more diagnosis of acquired hemophilia patient must be insured patient has provided written informed consent prior to enrolment patient compliant Exclusion Criteria: constitutional hemophilia chemotherapy ongoing treatment with prednisone > 20mg further more 1 month ongoing treatment with prednisone >0.7 mg/d further more 10 days thrombocytopenia leukopenia chronic disease

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Active Comparator: Bras A<br>Steroid 1mg/kg/d and Cyclophosphamide 2mg/kg/d | Drug: Steroid + cyclophosphamide<br> <br> |
| Experimental: Bras B<br>Steroid 1mg/kg/d and Rituximab 375 mg/m2 every week during four weeks | Drug: Steroid + rituximab<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary objective | Demonstrate the inferiority of steroid combined with rituximab as compared to the recommended immunosuppressive approach (steroid combined with cysclophosphamide for 21 to 42 days) as the first-line immunosuppressive therapy for FVIII inhibitor eradication in acquired haemophilia | During 18 months | 
| Primary efficacy outcome | The primary efficacy outcome is the proportion of patients achieving complete remission defined as titer FVII inhibitor lower than 0.4 Bethesda unit and factor VIII level > 50% | During 18 months | 
| Primary safety outcomes | The primary safety outcomes will be the occurrence of major bleeding and infection related immunosuppressive treatment adverse events. | During 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary objective | Secondary objective are time to complete remission, number of relapse at M6, M12, M18, adverse events (especially related to bleeding or to immunosuppressive treatment) and mortality | 6 months, 12 months and 18 months | 
| Other key safety outcome | The other key safety outcome are clinically relevant non major bleeding, diabetes and mortality non-related with acquired haemophilia or immunosuppressive therapy | During 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acquired haemophilia, Comparative and randomized study, Cyclophosphamide, Rituximab