Acquired Hemophilia APhase 4NCT03384277
Trial of Acquired Haemophilia With Steroid Combined With Cyclophosphamide Versus Steroid Combined With Rituximab
A Phase 4 study testing Steroid, Rituximab and Cyclophosphamide in people with Acquired Hemophilia A, run by Institute of Hematology & Blood Diseases Hospital, China at 1 site in China.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Acquired Hemophilia A
- What is being tested?
- Steroid, Rituximab and Cyclophosphamide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 1 siteChina
- Study dates
- 29 Dec 2017to 9 Jul 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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 locations and contacts
1 site in 1 country.
China1 site
Ethics Committee of Blood disease hospital, Chinese Academy of Medical Sciences
Tianjin, Tianjin Municipality, 300020
About this study
Official title: A Prospective, Randomized, Multicenter Clinical Trial of Acquired Haemophilia A With Steroid Combined With Cyclophosphamide Versus Steroid Combined With Rituximab
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
Read the 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.
- Conditions
- Acquired Hemophilia A
- Being tested
- Steroid, Rituximab, Cyclophosphamide
- Keywords
- Acquired hemophilia A, Cyclophosphamide, Rituximab, Steroid
- Medical subject headings
- Factor 8 deficiency, acquired
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SteroidDrug
Also called Corticosteroid
Methylprednisolone 0.8 mg/kg/day (or equivalent corticosteroid doses) for 3 weeks（then tapering gradually, 8 weeks in total）
RituximabDrug
375mg/m2 for one dose
CyclophosphamideDrug
cyclophosphamide 2 mg/kg/day until inhibitor negative (no longer than five weeks)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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) Receives: Drug: Steroid; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: During 18 months
Secondary outcomes (1)
Relapse rate and time to relapse
The proportion of patients who relapse and the time to relapse of each regimen will be measured.
Measured: During 18 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Dec 2017
- Study start29 Dec 2017
- Primary completion9 Jun 2022
- Study completion9 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Acquired Hemophilia AStudies of the same condition, open and under way.
- More trials run by Institute of Hematology & Blood Diseases Hospital, ChinaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Qilu Hospital of Shandong University, Tianjin First Central Hospital, The Second Affiliated Hospital of Kunming Medical University, Henan Cancer Hospital
- Responsible party
- Sponsor
- Investigators
- Lei Zhang, MD, Principal investigator, Blood disease hospital, Chinese academy of medical sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03384277
- Sponsor's protocol ID
- IIT2017006
- Status last verified
- Jun 2023
- First submitted
- 28 Nov 2017
- Last updated
- 11 Feb 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data for all primary and secondary outcome will be made available
Publications
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.
PubMed 20529258Collins 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.
PubMed 17047148Lottenberg 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.
PubMed 3109341Collins 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.
PubMed 22517903Stasi 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.
PubMed 14996701Wang 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.
PubMed 37851608
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Randomized, Multicenter Clinical Trial of Acquired Haemophilia A With Steroid Combined With Cyclophosphamide Versus Steroid Combined With Rituximab
- ClinicalTrials.gov ID
- NCT03384277
- Acronym / sponsor ID
- IIT2017006
- Conditions
- Acquired Hemophilia A
- Keywords
- Acquired hemophilia A, Cyclophosphamide, Rituximab, Steroid
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Institute of Hematology & Blood Diseases Hospital, ChinaUniversity, hospital or other
- Collaborators
- Qilu Hospital of Shandong University, Tianjin First Central Hospital, The Second Affiliated Hospital of Kunming Medical University, Henan Cancer Hospital
- Study start
- 29 Dec 2017 (actual)
- Primary completion
- 9 Jun 2022 (actual)
- Study completion
- 9 Jul 2022 (actual)
- First posted
- 27 Dec 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Steroid+Rituximab | Experimental | Drug: Steroid, Drug: RituximabMethylprednisolone 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. |
| Steroid +Cyclophosphamide | Active comparator | Drug: Steroid, Drug: CyclophosphamideMethylprednisolone 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) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 18-80 years old
- Men or women
- Women post-menopausal or with ongoing contraception
- Diagnosis of acquired hemophilia A
- Patient must be insured
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SteroidAlso: CorticosteroidMethylprednisolone 0.8 mg/kg/day (or equivalent corticosteroid doses) for 3 weeks（then tapering gradually, 8 weeks in total） | Drug | Steroid +Cyclophosphamide, Steroid+Rituximab |
| Rituximab375mg/m2 for one dose | Drug | Steroid+Rituximab |
| Cyclophosphamidecyclophosphamide 2 mg/kg/day until inhibitor negative (no longer than five weeks) | Drug | Steroid +Cyclophosphamide |
Primary outcome
Proportion of inhibitor eradication and time to attain first remission
Time frame: During 18 months
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.
1 secondary outcome
Relapse rate and time to relapse
Time frame: During 18 month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2026.
- Background: PubMed 20529258Collins 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.
- Background: PubMed 17047148Collins 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.
- Background: PubMed 3109341Lottenberg 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.
- Background: PubMed 22517903Collins 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.
- Background: PubMed 14996701Stasi 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.
- Derived from this study: PubMed 37851608Wang 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.
- Individual participant dataSharing planned: Yes. De-identified individual participant data for all primary and secondary outcome will be made available
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lei Zhang, MD principal investigator
Blood disease hospital, Chinese academy of medical sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Steroid, Rituximab and Cyclophosphamide in people with Acquired Hemophilia A, run by Institute of Hematology & Blood Diseases Hospital, China at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of inhibitor eradication and time to attain first remission (time frame: During 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03384277, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Feb 2026.