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

Anemia, Hemolytic, Autoimmune Clinical Trial

Official title:

Anti-CD20 Antibody Rituximab in Addition to Prednisolone in Treatment of Warm Antibody Related Autoimmune Hemolytic Anemia. A Randomised Danish Multicenter Trial.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01134432
• Other study ID #: AIHA-KA04062-gms
• Status: Completed
• Phase: Phase 3
• First received: May 28, 2010
• Last updated: September 9, 2013
• Start date: March 2005
• Est. completion date: July 2012

Study information

• Verified date: September 2013
• Source: Copenhagen University Hospital at Herlev
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Medicines Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Anemia
• Anemia, Hemolytic
• Anemia, Hemolytic, Autoimmune
• Hemolysis

Intervention

Drug:
• prednisolone + mabthera
Prednisolone: 1,5 mg/kg for two weeks with gradually reduced dosis over two months. Mabthera: 375 mg/m2 once a week for four weeks
• Prednisolone
Prednisolone: 1,5 mg/kg for two weeks and then gradually reduced dosis over two months

Locations

Country	Name	City	State
Denmark	Aalborg Hospital	Aalborg
Denmark	Rigshospitalet - Copenhagen University Hospital	Copenhagen
Denmark	Esbjerg Sygehus	Esbjerg
Denmark	Haderslev Sygehus	Haderslev
Denmark	Department of Haematology, Herlev Hospital	Herlev
Denmark	Holstebro Sygehus	Holstebro
Denmark	Naestved Sygehus	Naestved
Denmark	Odense University Hospital	Odense
Denmark	Roskilde Hospital	Roskilde
Denmark	Vejle Hospital	Vejle
Denmark	Viborg Sygehus	Viborg

Sponsors (1)

Lead Sponsor	Collaborator
Copenhagen University Hospital at Herlev

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients in each group in complete or partial remission		End of treatment and follow-up for 12 months	No
Secondary	Side effects		End of treatment plus follow-up for 12 months	Yes