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

Acquired Hemophilia A Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03384277
• Other study ID #: IHBDH-IIT2017006
• Status: Completed
• Phase: Phase 4
• Start date: December 29, 2017
• Est. completion date: July 9, 2022

Study information

• Verified date: June 2023
• Source: Institute of Hematology & Blood Diseases Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: July 9, 2022
• Est. primary completion date: June 9, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Acquired Hemophilia A
• Hemophilia A

Intervention

Drug:
• 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
• Cyclophosphamide
cyclophosphamide 2 mg/kg/day until inhibitor negative (no longer than five weeks)

Locations

Country	Name	City	State
China	Ethics Committee of Blood disease hospital, Chinese Academy of Medical Sciences	Tianjin	Tianjin

Sponsors (5)

Lead Sponsor	Collaborator
Zhang Lei, MD	Henan Cancer Hospital, Qilu Hospital of Shandong University, The Second Affiliated Hospital of Kunming Medical University, Tianjin First Central Hospital

Country where clinical trial is conducted

China, 

References & Publications (5)

Collins P, Baudo F, Huth-Kuhne A, Ingerslev J, Kessler CM, Castellano ME, Shima M, St-Louis J, Levesque H. Consensus recommendations for the diagnosis and treatment of acquired hemophilia A. BMC Res Notes. 2010 Jun 7;3:161. doi: 10.1186/1756-0500-3-161. — View Citation

Collins P, Baudo F, Knoebl P, Levesque H, Nemes L, Pellegrini F, Marco P, Tengborn L, Huth-Kuhne A; EACH2 registry collaborators. Immunosuppression for acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2). Blood. 2012 Jul 5;120(1):47-55. doi: 10.1182/blood-2012-02-409185. Epub 2012 Apr 18. — View Citation

Collins PW, Hirsch S, Baglin TP, Dolan G, Hanley J, Makris M, Keeling DM, Liesner R, Brown SA, Hay CR; UK Haemophilia Centre Doctors' Organisation. Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors' Organisation. Blood. 2007 Mar 1;109(5):1870-7. doi: 10.1182/blood-2006-06-029850. Epub 2006 Oct 17. — View Citation

Lottenberg R, Kentro TB, Kitchens CS. Acquired hemophilia. A natural history study of 16 patients with factor VIII inhibitors receiving little or no therapy. Arch Intern Med. 1987 Jun;147(6):1077-81. doi: 10.1001/archinte.147.6.1077. — View Citation

Stasi R, Brunetti M, Stipa E, Amadori S. Selective B-cell depletion with rituximab for the treatment of patients with acquired hemophilia. Blood. 2004 Jun 15;103(12):4424-8. doi: 10.1182/blood-2003-11-4075. Epub 2004 Mar 2. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Infection of two regimens	The safety outcomes will be the occurrence of infection related to immunosuppressive treatment adverse events.	During 18 months
Other	Hemocytopenia of two regimens	The safety outcomes will be the occurrence of Hemocytopenia related to immunosuppressive treatment adverse events.	During 18 month
Primary	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	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