Prednisolone +/- Addition of Anti-CD20 Antibody, Rituximab, in Patients With Immune Hemolytic Anemia

Condition(s) targeted: Anemia, Hemolytic, Autoimmune

Intervention: prednisolone + mabthera (Drug); Prednisolone (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Copenhagen University Hospital at Herlev

Official(s) and/or principal investigator(s):
Henrik S Birgens, MD, Principal Investigator, Affiliation: Department of Haematology (L121), Copenhagen University Hospital Herlev

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.

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 design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Number of patients in each group in complete or partial remission

Secondary outcome: Side effects

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Aalborg Hospital, Aalborg DK-9000, Denmark

Rigshospitalet - Copenhagen University Hospital, Copenhagen DK-2100, Denmark

Esbjerg Sygehus, Esbjerg DK-6700, Denmark

Haderslev Sygehus, Haderslev DK-6100, Denmark

Department of Haematology, Herlev Hospital, Herlev DK-2730, Denmark

Holstebro Sygehus, Holstebro DK-7500, Denmark

Naestved Sygehus, Naestved DK-4700, Denmark

Odense University Hospital, Odense DK-5000, Denmark

Roskilde Hospital, Roskilde DK-4000, Denmark

Vejle Hospital, Vejle DK-7100, Denmark

Viborg Sygehus, Viborg DK-8800, Denmark

Starting date: March 2005
Last updated: September 9, 2013