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Rituximab in Auto-Immune Hemolytic Anemia (RAHIA)

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ClinicalTrials.gov Identifier: NCT01181154
Recruitment Status : Completed
First Posted : August 13, 2010
Last Update Posted : October 19, 2017
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Tracking Information
First Submitted Date  ICMJE August 12, 2010
First Posted Date  ICMJE August 13, 2010
Last Update Posted Date October 19, 2017
Actual Study Start Date  ICMJE March 3, 2011
Actual Primary Completion Date January 8, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 12, 2010)
Overall response rate (complete and partial response) in both arms [ Time Frame: at 1 year ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 12, 2010)
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Rituximab in Auto-Immune Hemolytic Anemia
Official Title  ICMJE Rituximab in Adult's Warm Auto-Immune Hemolytic Anemia : a Phase III, Double-bind, Randomised Placebo-controlled Trial
Brief 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).
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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Warm Autoimmune Hemolytic Anemia
Intervention  ICMJE
  • Drug: rituximab (Mabthera®)
    1000 mg at day 1 and day 15
    Other Name: rituximab (Mabthera®)1000 mg at day 1 and day 15
  • Drug: Placebo
    equivalent volume total
    Other Name: Placebo equivalent volume total
Study Arms  ICMJE
  • Placebo Comparator: equivalent volume total (=1000 ml)
    Placebo : equivalent volume total (=1000 ml)
    Intervention: Drug: Placebo
  • Experimental: rituximab (Mabthera®)
    rituximab (Mabthera®), 1000 mg at day 1 and day 15
    Intervention: Drug: rituximab (Mabthera®)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 12, 2010)
32
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE January 8, 2016
Actual Primary Completion Date January 8, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age > 18 years
  2. 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).
  3. 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.
  4. 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.
  5. Normal level gammaglobulins in the serum (i.e. >5g/L) at inclusion.
  6. Absence of detectable lymph nodes on a total body CT-scan (to be performed before inclusion if not performed at diagnosis).
  7. Effective means of contraception during treatment and for six months after completion of treatment for all women of child bearing age
  8. Negative serum pregnancy test within 14 days prior to study entry.
  9. Written informed consent

Exclusion Criteria:

Previous treatment with rituximab

  1. 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
  2. Ongoing immunosuppressive therapy (other than corticosteroids) or previous treatment administered within 2 weeks prior to the beginning of the study treatment
  3. Non-Hodgkin Lymphoma (NHL) other than stage A chronic lymphoid leukemia
  4. 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.
  5. Autoimmune disorder such as SLE with at least one extra-hematological manifestation requiring a treatment with steroids and/or immunosuppressive drugs.
  6. Any other associated cause congenital or acquired hemolytic anemia (except thalassemia trait or heterozygous sickle cell anemia).
  7. Negative DAT or DAT positive with isolated anti-C3d pattern related to the presence of a monoclonal IgM with cold agglutinin properties.
  8. Positive HIV test and/or hepatitis virus C infection and/or positive hepatitis B virus surface antigen (HbsAg).
  9. Neutrophils count < 1,000/mm 3 at inclusion.
  10. Impaired renal function as indicated by a serum creatinine level > 2 mg/d
  11. 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.
  12. New York Heart Classification III or IV heart disease.
  13. Previous history of severe psychiatric disorder or are unable to comply with study and follow-up procedures
  14. Pregnant or lactating women, or woman planning to become pregnant within 12 months of receiving study drug
  15. Absence of written informed consent.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01181154
Other Study ID Numbers  ICMJE P080704
2008-008255-42 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Assistance Publique - Hôpitaux de Paris
Study Sponsor  ICMJE Assistance Publique - Hôpitaux de Paris
Collaborators  ICMJE Hoffmann-La Roche
Investigators  ICMJE
Principal Investigator: Marc MICHEL, MD Assistance Publique - Hôpitaux de Paris
PRS Account Assistance Publique - Hôpitaux de Paris
Verification Date October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP