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

NCT03384277 | Completed Phase 4

• 1 other identifier: IIT2017006
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

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

Conditions

Acquired Hemophilia A

Keywords

Acquired hemophilia A; Cyclophosphamide; Rituximab; Steroid

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Relapse rate and time to relapse

  During 18 month

Other Outcomes (2)

• Infection of two regimens

  During 18 months

• Hemocytopenia of two regimens

  During 18 month

Study Arms (2)

Steroid+Rituximab

EXPERIMENTAL

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; Drug: Rituximab

Steroid +Cyclophosphamide

ACTIVE COMPARATOR

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; Drug: Cyclophosphamide

Interventions

Steroid DRUG

Methylprednisolone 0.8 mg/kg/day (or equivalent corticosteroid doses) for 3 weeks（then tapering gradually, 8 weeks in total）

Also known as: Corticosteroid

Steroid +Cyclophosphamide; Steroid+Rituximab

Rituximab DRUG

375mg/m2 for one dose

Steroid+Rituximab

Cyclophosphamide DRUG

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

Steroid +Cyclophosphamide

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Qilu Hospital of Shandong University: collaborator
• Tianjin First Central Hospital: collaborator
• Institute of Hematology & Blood Diseases Hospital, China: lead
• The Second Affiliated Hospital of Kunming Medical University: collaborator
• Henan Cancer Hospital: collaborator

Study Sites (1)

Ethics Committee of Blood disease hospital, Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, 300020, China

Location

Related Publications (6)

• 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.

  PMID: 20529258 BACKGROUND

• 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.

  PMID: 17047148 BACKGROUND

• 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.

  PMID: 3109341 BACKGROUND

• 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.

  PMID: 22517903 BACKGROUND

• 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.

  PMID: 14996701 BACKGROUND

• Wang P, Zhou R, Xue F, Zhou H, Bai J, Wang X, Ma Y, Song Z, Chen Y, Liu X, Fu R, Sun T, Ju M, Dai X, Dong H, Yang R, Liu W, Zhang L. Single-dose rituximab plus glucocorticoid versus cyclophosphamide plus glucocorticoid in patients with newly diagnosed acquired hemophilia A: A multicenter, open-label, randomized noninferiority trial. Am J Hematol. 2024 Jan;99(1):28-37. doi: 10.1002/ajh.27128. Epub 2023 Oct 18.

  PMID: 37851608 DERIVED

MeSH Terms

Conditions

Factor 8 deficiency, acquired

Interventions

Steroids; Adrenal Cortex Hormones; Rituximab; Cyclophosphamide

Intervention Hierarchy (Ancestors)

Fused-Ring Compounds; Polycyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Lei Zhang, MD

  Blood disease hospital, Chinese academy of medical sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2017
• First Posted: December 27, 2017
• Study Start: December 29, 2017
• Primary Completion: June 9, 2022
• Study Completion: July 9, 2022
• Last Updated: February 11, 2026

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: Data will be available within 6 month of study completion
• Access Criteria: Data access requests will be reviewed by an external independent Review Panel. Requests will be required to sign a Data Access Agreement

Locations

CN (1)