Warm Autoimmune Hemolytic AnemiaPhase 3RAHIANCT01181154
Rituximab in Auto-Immune Hemolytic Anemia
A Phase 3 study testing rituximab (Mabthera®) in people with Warm Autoimmune Hemolytic Anemia, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Warm Autoimmune Hemolytic Anemia
- What is being tested?
- rituximab (Mabthera®)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 1 siteFrance
- Study dates
- 3 Mar 2011to 8 Jan 2016
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Rituximab in Adult's Warm Auto-Immune Hemolytic Anemia : a Phase III, Double-bind, Randomised Placebo-controlled Trial
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).
Read the 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).
- Conditions
- Warm Autoimmune Hemolytic Anemia
- Being tested
- rituximab (Mabthera®), Placebo
- Keywords
- Auto-Immune, Hemolytic, Anemia, AHA, AIHA, Rituximab
- Medical subject headings
- Hemolysis, Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rituximab (Mabthera®)Drug
Also called rituximab (Mabthera®)1000 mg at day 1 and day 15
1000 mg at day 1 and day 15
PlaceboDrug
Also called Placebo equivalent volume total
equivalent volume total
| Study group | Role | What they receive |
|---|---|---|
| equivalent volume total (=1000 ml) | Placebo comparator | Placebo : equivalent volume total (=1000 ml) Receives: Drug: Placebo |
| rituximab (Mabthera®) | Experimental | rituximab (Mabthera®), 1000 mg at day 1 and day 15 Receives: Drug: rituximab (Mabthera®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate (complete and partial response) in both arms
Measured: at 1 year
Secondary outcomes (7)
Comparison in both arms of the mean cumulative doses of prednisone
Measured: at 1 year
Comparison in both arms of the number of transfusions of packed red blood cells in both arms
Measured: at 1 year
Comparison in both arms of the number of days in hospital
Measured: within the first year of follow-up
Comparison in both arms of the number of patients requiring a splenectomy and/or an immunosuppressor
Measured: during the first 12 months of follow-up
Comparison in both arm of the mortality
Measured: at 1 year
Comparison in both arm of overall response (CR + PR)
Measured: at 2 years
Comparison of the incidence of serious side effects in both arms
Measured: at 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2010 (estimated)
- Study start3 Mar 2011
- Primary completion8 Jan 2015
- Study completion8 Jan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Warm Autoimmune Hemolytic AnemiaStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Hoffmann-La Roche
- Responsible party
- Sponsor
- Investigators
- Marc MICHEL, MD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01181154
- Sponsor's protocol ID
- P080704
- Other IDs
- 2008-008255-42, 2008
- Acronym
- RAHIA
- Status last verified
- Oct 2017
- First submitted
- 12 Aug 2010
- Last updated
- 19 Oct 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rituximab in Adult's Warm Auto-Immune Hemolytic Anemia : a Phase III, Double-bind, Randomised Placebo-controlled Trial
- ClinicalTrials.gov ID
- NCT01181154
- Acronym / sponsor ID
- RAHIA / P080704
- Conditions
- Warm Autoimmune Hemolytic Anemia
- Keywords
- Auto-Immune, Hemolytic, Anemia, AHA, AIHA, Rituximab
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Hoffmann-La Roche
- Study start
- 3 Mar 2011 (actual)
- Primary completion
- 8 Jan 2015 (actual)
- Study completion
- 8 Jan 2016 (actual)
- First posted
- 13 Aug 2010 (estimated)
- 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.
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).
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| equivalent volume total (=1000 ml) | Placebo comparator | Drug: PlaceboPlacebo : equivalent volume total (=1000 ml) |
| rituximab (Mabthera®) | Experimental | Drug: rituximab (Mabthera®)rituximab (Mabthera®), 1000 mg at day 1 and day 15 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (16 listed)
- 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.
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 |
|---|---|---|
| rituximab (Mabthera®)Also: rituximab (Mabthera®)1000 mg at day 1 and day 151000 mg at day 1 and day 15 | Drug | rituximab (Mabthera®) |
| PlaceboAlso: Placebo equivalent volume totalequivalent volume total | Drug | equivalent volume total (=1000 ml) |
Primary outcome
Overall response rate (complete and partial response) in both arms
Time frame: at 1 year
7 secondary outcomes
Comparison in both arms of the mean cumulative doses of prednisone
Time frame: 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
Comparison in both arms of the number of days in hospital
Time frame: 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
Comparison in both arm of the mortality
Time frame: at 1 year
Comparison in both arm of overall response (CR + PR)
Time frame: at 2 years
Comparison of the incidence of serious side effects in both arms
Time frame: at 1 year
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 19 Oct 2017.
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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.
Marc MICHEL, MD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing rituximab (Mabthera®) in people with Warm Autoimmune Hemolytic Anemia, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 9 inclusion and 16 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 19 Oct 2017. 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 France. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Overall response rate (complete and partial response) in both arms (time frame: at 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Oct 2017.