Back to results

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

Primary Purpose

Acquired Hemophilia A

Status

Completed

Phase

Phase 4

Locations

China

Study Type

Interventional

Intervention

Steroid

Rituximab

Cyclophosphamide

About this trial

This is an interventional treatment trial for Acquired Hemophilia A focused on measuring Acquired hemophilia A, Cyclophosphamide, Rituximab, Steroid

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Steroid+Rituximab

Steroid +Cyclophosphamide

Arm 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.

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)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Relapse rate and time to relapse

The proportion of patients who relapse and the time to relapse of each regimen will be measured.

Full Information

NCT ID

NCT03384277

First Posted

November 28, 2017

Last Updated

June 14, 2023

Sponsor

Zhang Lei, MD

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT03384277

Brief Title

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

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Completed

Study Start Date

December 29, 2017 (Actual)

Primary Completion Date

June 9, 2022 (Actual)

Study Completion Date

July 9, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Zhang Lei, MD

Collaborators

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

5. 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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acquired Hemophilia A

Keywords

Acquired hemophilia A, Cyclophosphamide, Rituximab, Steroid

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

66 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Steroid+Rituximab

Arm Type

Experimental

Arm 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.

Arm Title

Steroid +Cyclophosphamide

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Steroid

Other Intervention Name(s)

Corticosteroid

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Rituximab

Intervention Description

375mg/m2 for one dose

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Intervention Description

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

Primary Outcome Measure Information:

Title

Proportion of inhibitor eradication and time to attain first remission

Description

Time Frame

During 18 months

Secondary Outcome Measure Information:

Title

Relapse rate and time to relapse

Description

The proportion of patients who relapse and the time to relapse of each regimen will be measured.

Time Frame

During 18 month

Other Pre-specified Outcome Measures:

Title

Infection of two regimens

Description

The safety outcomes will be the occurrence of infection related to immunosuppressive treatment adverse events.

Time Frame

During 18 months

Title

Hemocytopenia of two regimens

Description

The safety outcomes will be the occurrence of Hemocytopenia related to immunosuppressive treatment adverse events.

Time Frame

During 18 month

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Lei Zhang, MD

Organizational Affiliation

Blood disease hospital, Chinese academy of medical sciences

Official's Role

Principal Investigator

Facility Information:

Facility Name

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

City

Tianjin

State/Province

Tianjin

ZIP/Postal Code

300020

Country

China

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

De-identified individual participant data for all primary and secondary outcome will be made available

IPD Sharing Time Frame

Data will be available within 6 month of study completion

IPD Sharing Access Criteria

Data access requests will be reviewed by an external independent Review Panel. Requests will be required to sign a Data Access Agreement

IPD Sharing URL

http://www.medresman.org

Citations:

PubMed Identifier

20529258

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.

Results Reference

background

PubMed Identifier

17047148

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.

Results Reference

background

PubMed Identifier

3109341

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.

Results Reference

background

PubMed Identifier

22517903

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.

Results Reference

background

PubMed Identifier

14996701

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.

Results Reference

background

Learn more about this trial

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

We'll reach out to this number within 24 hrs