- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01181154
Rituximab in Auto-Immune Hemolytic Anemia (RAHIA)
Rituximab in Adult's Warm Auto-Immune Hemolytic Anemia : a Phase III, Double-bind, Randomised Placebo-controlled Trial
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The primary aim of the study is to assess the efficacy (overall response rate at 1 year) of rituximab (an anti-CD20 monoclonal antibody) in AIHA due to warm autoantibody when administered at the initial phase of the disease. All eligible patents with a newly diagnosed AIHA (within 6 weeks after diagnosis) will be treated by corticosteroids at standard dose (prednisone 1 mg/kg/day) and will be randomized into 2 arms: Rituximab or placebo 1000 mg on days 1 and 15 in a 1/1 ratio. As soon as at least a partial remission (PR) of AIHA will be achieved, the daily dose of prednisone will be tapered following the rules provided by the protocol.
The hypothesis based on retrospective data is that, the rate of overall response-rate (PR + CR) at 1 year will be much higher in the rituximab arm (80%) than in the placebo arm (20%).Thirty four patients (17 in each arm) will be include (amendment n°6 - 15/10/2013) over a 3 year period (amendment n°3 - 11/12/2012).
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
-
Créteil, France, 94000
- Henri Mondor University Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age > 18 years
- AIHA defined at time of diagnosis by a Hgb level £ 10 g/dL, with a reticulocytes count > 120 109/L, signs of hemolysis (at least a haptoglobin level < 4 mg/L), and a positive direct antiglobulin test (DAT) ( IgG or IgG + complement pattern).
- Disease duration equal or less than 6 weeks at time of inclusion --> removed by amendment n°4 and substituted by :First episode of AIHA to "hot" antibody previously untreated or treated corticosteroids for less than 6 weeks.
- Patients with an associated autoimmune thrombocytopenia (Evans' syndrome) will be eligible for the study if the platelet count is over 30 x 109/L at inclusion.
- Normal level gammaglobulins in the serum (i.e. >5g/L) at inclusion.
- Absence of detectable lymph nodes on a total body CT-scan (to be performed before inclusion if not performed at diagnosis).
- Effective means of contraception during treatment and for six months after completion of treatment for all women of child bearing age
- Negative serum pregnancy test within 14 days prior to study entry.
- Written informed consent
Exclusion Criteria:
Previous treatment with rituximab
- AIHA diagnosed and treated more than 6 weeks prior to inclusion removed by amendment n°4 and substituted by AIHA relapsed or newly diagnosed but treated with corticosteroids for more than 6 weeks
- Ongoing immunosuppressive therapy (other than corticosteroids) or previous treatment administered within 2 weeks prior to the beginning of the study treatment
- Non-Hodgkin Lymphoma (NHL) other than stage A chronic lymphoid leukemia
- Previous or concomitant malignancy other than basal cell or squamous cell carcinoma of the skin, carcinoma-in-situ of the cervix, or other malignancy for which the patient had not been disease-free for at least 5 years.
- Autoimmune disorder such as SLE with at least one extra-hematological manifestation requiring a treatment with steroids and/or immunosuppressive drugs.
- Any other associated cause congenital or acquired hemolytic anemia (except thalassemia trait or heterozygous sickle cell anemia).
- Negative DAT or DAT positive with isolated anti-C3d pattern related to the presence of a monoclonal IgM with cold agglutinin properties.
- Positive HIV test and/or hepatitis virus C infection and/or positive hepatitis B virus surface antigen (HbsAg).
- Neutrophils count < 1,000/mm 3 at inclusion.
- Impaired renal function as indicated by a serum creatinine level > 2 mg/d
- Inadequate liver function as indicated by a total bilirubin level > 2.0 mg/dL and/or an AST or ALT level > 2x upper limit of normal.
- New York Heart Classification III or IV heart disease.
- Previous history of severe psychiatric disorder or are unable to comply with study and follow-up procedures
- Pregnant or lactating women, or woman planning to become pregnant within 12 months of receiving study drug
- Absence of written informed consent.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: equivalent volume total (=1000 ml)
Placebo : equivalent volume total (=1000 ml)
|
equivalent volume total
Other Names:
|
Experimental: rituximab (Mabthera®)
rituximab (Mabthera®), 1000 mg at day 1 and day 15
|
1000 mg at day 1 and day 15
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Overall response rate (complete and partial response) in both arms
Time Frame: at 1 year
|
at 1 year
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Comparison in both arms of the mean cumulative doses of prednisone
Time Frame: at 1 year
|
at 1 year
|
Comparison in both arms of the number of transfusions of packed red blood cells in both arms
Time Frame: at 1 year
|
at 1 year
|
Comparison in both arms of the number of days in hospital
Time Frame: within the first year of follow-up
|
within the first year of follow-up
|
Comparison in both arms of the number of patients requiring a splenectomy and/or an immunosuppressor
Time Frame: during the first 12 months of follow-up
|
during the first 12 months of follow-up
|
Comparison in both arm of the mortality
Time Frame: at 1 year
|
at 1 year
|
Comparison in both arm of overall response (CR + PR)
Time Frame: at 2 years
|
at 2 years
|
Comparison of the incidence of serious side effects in both arms
Time Frame: at 1 year
|
at 1 year
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Marc MICHEL, MD, Assistance Publique - Hôpitaux de Paris
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- P080704
- 2008-008255-42 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Warm Autoimmune Hemolytic Anemia
-
SanofiActive, not recruitingWarm Autoimmune Hemolytic Anemia (wAIHA)United States, Austria, China, Denmark, Germany, Hungary, Italy, Spain, United Kingdom
-
SanofiTerminatedWarm Autoimmune Hemolytic Anemia (wAIHA)United Kingdom, Belgium, Netherlands, France, United States, Germany, Hungary, Italy
-
Novartis PharmaceuticalsRecruitingWarm Autoimmune Hemolytic Anemia (wAIHA)China, Japan, Spain, Singapore, France, Germany, Taiwan, United States, Italy, India, Malaysia, Argentina, Hungary, Israel, Australia, Thailand, United Kingdom, Romania
-
Annexon, Inc.CompletedWarm Autoimmune Hemolytic Anemia (wAIHA)United States
-
Eugene NikitinUnknownAIHA - Warm Autoimmune Hemolytic AnemiaRussian Federation
-
Incyte CorporationActive, not recruitingWarm Autoimmune Hemolytic Anemia (wAIHA)Spain, United States, Austria, Belgium, Canada, France, Germany, Israel, Italy, Japan, Netherlands, Poland, United Kingdom
-
Peking Union Medical College HospitalRecruiting
-
Alexion PharmaceuticalsWithdrawnWarm Autoimmune Hemolytic AnemiaUnited States
-
Alexion PharmaceuticalsTerminatedWarm Autoimmune Hemolytic AnemiaUnited States, Jordan
-
Chen MiaoRecruiting
Clinical Trials on Placebo
-
SamA Pharmaceutical Co., LtdUnknownAcute Bronchitis | Acute Upper Respiratory Tract InfectionKorea, Republic of
-
National Institute on Drug Abuse (NIDA)CompletedCannabis UseUnited States
-
AstraZenecaParexel; Spandauer Damm 130; 14050; Berlin, GermanyCompletedMale Subjects With Type II Diabetes (T2DM)Germany
-
Heptares Therapeutics LimitedCompletedPharmacokinetics | Safety IssuesUnited Kingdom
-
GlaxoSmithKlineCompletedPulmonary Disease, Chronic ObstructiveUnited Kingdom, Netherlands
-
Shijiazhuang Yiling Pharmaceutical Co. LtdXuanwu Hospital, BeijingCompleted
-
GlaxoSmithKlineCompletedInfections, BacterialUnited States
-
ItalfarmacoCompletedBecker Muscular DystrophyNetherlands, Italy
-
West Penn Allegheny Health SystemCompletedAsthma | Allergic RhinitisUnited States