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

Zhang Lei, MD

Status and phase: Completed; Phase 4

Conditions: Acquired Hemophilia A

Treatments: Drug: Cyclophosphamide; Drug: Rituximab; Drug: Steroid

Study type: Interventional

Funder types: Other

Identifiers

NCT03384277

IHBDH-IIT2017006

Details and patient eligibility

About

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

Full 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.

Enrollment: 66 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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66 participants in 2 patient groups

Steroid+Rituximab

Experimental group

Description:

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.

Treatment:

Drug: Steroid

Drug: Rituximab

Steroid +Cyclophosphamide

Active Comparator group

Description:

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)

Treatment:

Drug: Steroid

Drug: Cyclophosphamide