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

Sponsor

Zhang Lei (Other)

Overall Status

Unknown status

CT.gov ID

NCT03384277

Collaborator

Qilu Hospital of Shandong University (Other), Tianjin First Central Hospital (Other), The Second Affiliated Hospital of Kunming Medical University (Other), Henan Cancer Hospital (Other)

100

Enrollment

Location

Arms

49.2

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Acquired Hemophilia A	Drug: Steroid Drug: Rituximab Drug: Cyclophosphamide	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 26, 2017

Anticipated Primary Completion Date :

Oct 30, 2021

Anticipated Study Completion Date :

Dec 1, 2021

Arms and Interventions

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)

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)

Outcome Measures

Primary Outcome Measures

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

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.

Other Outcome Measures

Infection of two regimens [During 18 months]
The safety outcomes will be the occurrence of infection related to immunosuppressive treatment adverse events.
Hemocytopenia of two regimens [During 18 month]
The safety outcomes will be the occurrence of Hemocytopenia related to immunosuppressive treatment adverse events.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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