Clinical trial NCT01134432: Prednisolone +/- Addition of Anti-CD20 Antibody, Rituximab, in Patients With Immune Hemolytic Anemia
Official title: Anti-CD20 Antibody Rituximab in Addition to Prednisolone in Treatment of Warm Antibody Related Autoimmune Hemolytic Anemia. A Randomised Danish Multicenter Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anemia, Hemolytic, Autoimmune
Keywords: autoimmune hemolytic anemia
hemolytic anemia
Rituximab
Treatment of autoimmune hemolytic anemia
warm antibody dependant autoimmune hemolytic anemia
Lead sponsor: Copenhagen University Hospital at Herlev
Sponsor class: OTHER
First posted: 2010-06-02
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The conventional treatment in warm-antibody dependent autoimmune haemolytic anaemia (AIHA) is high-dose glucocorticoid, but in more than half of the patients, haemolytic activity will recur after end of treatment or during the gradual reduction in dose of the drug. As a result, many patients will finally be splenectomized or be treated with long-term glucocorticoids or other immunosuppressive drugs as azathioprine or cyclophosphamide. Recent studies have shown however, that some patients will respond to treatment with the chimeric anti-CD 20 antibody Rituximab and is some cases, the response is permanent. In most of the studies, Rituximab has been used in refractory disease or at least as second line treatment. In this study, patients with AIHA are randomized to receive either high-dose prednisolone with gradual reduction in dose over 2-3 months alone or in combination with Rituximab 375 mg/m2 once a week for 4 weeks. The efficacy of Rituximab will be evaluated by a comparison of the patients in the two treatment arms. The primary treatment goal is a reduction in the number of patients who obtain long-term complete or partial remission. The secondary treatment goal is a reduction in patients who will be splenectomised or receive other immunosuppressive drugs. Finally a comparison of side effects of the treatments will take place.


Eligibility criteria: Inclusion Criteria:

* Age 18 years or over
* Clinical and biochemical signs of haemolytic anaemia
* Positive Coombs test with anti-IgG on its own or with anti-CD3d
* Adequate contraceptive measures (intrauterine device, contraceptive pill or gestagen deposit) for women of childbearing potential

Exclusion Criteria:

* Performance status \> 2
* Previous treatment with Rituximab
* Other immune suppressive or anti neoplastic treatment including prednisolone within 3 months
* Auto immune haemolytic anaemia within 6 months
* Other serious disease
* Pregnant women and nursing mothers. Adequate contraceptive measures must be taken for the duration of the study.
* Contraindication for treatment with Rituximab, i.e. patients that develop hypersensitivity/allergy to the contents of the drug or have antibodies against murine proteins.
* Active infection which requires antibiotic treatment

Primary outcomes:
measure: Number of patients in each group in complete or partial remission
timeFrame: End of treatment and follow-up for 12 months
Secondary outcomes:
measure: Side effects
timeFrame: End of treatment plus follow-up for 12 months
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Aalborg Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet - Copenhagen University Hospital
city: Esbjerg
country: Denmark
facility: Esbjerg Sygehus
city: Haderslev
country: Denmark
facility: Haderslev Sygehus
city: Herlev
country: Denmark
facility: Department of Haematology, Herlev Hospital
city: Holstebro
country: Denmark
facility: Holstebro Sygehus
city: Naestved
country: Denmark
facility: Naestved Sygehus
city: Odense
country: Denmark
facility: Odense University Hospital
city: Roskilde
country: Denmark
facility: Roskilde Hospital
city: Vejle
country: Denmark
facility: Vejle Hospital
city: Viborg
country: Denmark
facility: Viborg Sygehus
Study officials:
affiliation: Department of Haematology (L121), Copenhagen University Hospital Herlev
name: Henrik S Birgens, MD
role: PRINCIPAL_INVESTIGATOR
References: