Clinical trial NCT03384277: Trial of Acquired Haemophilia With Steroid Combined With Cyclophosphamide Versus Steroid Combined With Rituximab
Official title: A Prospective, Randomized, Multicenter Clinical Trial of Acquired Haemophilia A With Steroid Combined With Cyclophosphamide Versus Steroid Combined With Rituximab
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acquired Hemophilia A
Keywords: Acquired hemophilia A
Cyclophosphamide
Rituximab
Steroid
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
Collaborators: name: Qilu Hospital of Shandong University
name: Tianjin First Central Hospital
name: The Second Affiliated Hospital of Kunming Medical University
name: Henan Cancer Hospital
First posted: 2017-12-27
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of inhibitor eradication and time to attain first remission
timeFrame: During 18 months
Secondary outcomes:
measure: Relapse rate and time to relapse
timeFrame: During 18 month
Other outcomes:
measure: Infection of two regimens
timeFrame: During 18 months
measure: Hemocytopenia of two regimens
timeFrame: During 18 month
Locations:
city: Tianjin
country: China
facility: Ethics Committee of Blood disease hospital, Chinese Academy of Medical Sciences
state: Tianjin
Study officials:
affiliation: Blood disease hospital, Chinese academy of medical sciences
name: Lei Zhang, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
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.
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.
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.