Rituximab in Auto-Immune Hemolytic Anemia (RAHIA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01181154
First received: August 12, 2010
Last updated: November 14, 2013
Last verified: November 2013
  Purpose

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).


Condition Intervention Phase
Warm Autoimmune Hemolytic Anemia
Drug: rituximab (Mabthera®)
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Rituximab in Adult's Warm Auto-Immune Hemolytic Anemia : a Phase III, Double-bind, Randomised Placebo-controlled Trial

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Overall response rate (complete and partial response) in both arms [ Time Frame: at 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Comparison in both arms of the mean cumulative doses of prednisone [ Time Frame: at 1 year ] [ Designated as safety issue: No ]
  • Comparison in both arms of the number of transfusions of packed red blood cells in both arms [ Time Frame: at 1 year ] [ Designated as safety issue: No ]
  • Comparison in both arms of the number of days in hospital [ Time Frame: within the first year of follow-up ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Comparison in both arm of the mortality [ Time Frame: at 1 year ] [ Designated as safety issue: No ]
  • Comparison in both arm of overall response (CR + PR) [ Time Frame: at 2 years ] [ Designated as safety issue: No ]
  • Comparison of the incidence of serious side effects in both arms [ Time Frame: at 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 32
Study Start Date: March 2011
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: equivalent volume total (=1000 ml)
Placebo : equivalent volume total (=1000 ml)
Drug: Placebo
equivalent volume total
Other Name: Placebo equivalent volume total
Experimental: rituximab (Mabthera®)
rituximab (Mabthera®), 1000 mg at day 1 and day 15
Drug: rituximab (Mabthera®)
1000 mg at day 1 and day 15
Other Name: rituximab (Mabthera®)1000 mg at day 1 and day 15

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 two patients (16 in each arm) will be include over a 2 year period.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01181154

Contacts
Contact: Marc MICHEL, MD 1 49 81 20 60 ext +33 marc.michel@hmn.aphp.fr

Locations
France
Henri Mondor University Hospital Recruiting
Créteil, France, 94000
Contact: Marc MICHEL, MD    1 49 81 20 60 ext +33    marc.michel@hmn.aphp.fr   
Contact: Salimatou SACKO, CRA    1 49 81 33 82 ext +33    salimatou.sacko@hmn.aphp.fr   
Principal Investigator: Marc MICHEL, MD         
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Hoffmann-La Roche
Investigators
Principal Investigator: Marc MICHEL, MD Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01181154     History of Changes
Other Study ID Numbers: P080704, 2008-008255-42
Study First Received: August 12, 2010
Last Updated: November 14, 2013
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Auto-Immune
Hemolytic
Anemia
AHA
AIHA
Rituximab

Additional relevant MeSH terms:
Anemia
Anemia, Hemolytic
Anemia, Hemolytic, Autoimmune
Hemolysis
Hematologic Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Rituximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 20, 2014