Clinical Trial: Therapy for Chronic Cold Agglutinin Disease

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Therapy for Chronic Cold Agglutinin Disease: A Prospective, Non-randomized International Multicentre Study on the Safety and Efficacy of Rituximab in Combination With Flud

Brief Summary: Chronic cold agglutinin disease (CAD) is a type of autoimmune hemolytic anemia (anemia due to destruction of red blood cells by abnormal antibodies). Almost all patients also suffer from cold-induced disturbances of blood circulation. The purpose of this study is to assess the efficacy and safety of combination therapy with rituximab (an antibody against B lymphocytes) and fludarabine (a cytotoxic drug) for CAD. Another aim is to try to assess whether these agents in combination are better than single agent therapy with rituximab.

Detailed Summary:

1. Background

Chronic cold agglutinin disease (CAD) is mediated by monoclonal cold-reactive autoantibodies that bind to erythrocyte surface antigens, causing haemagglutination and complement-mediated haemolysis. Anaemia is severe (Hb 8.0 g/dL or lower) in one-third of patients and complement-induced exacerbation during febrile illness occurs frequently 1-3. Cold-induced circulatory symptoms are present in more than 90% of patients and may be disabling 1. CAD not associated with overt lymphoma or other disease has traditionally been classified as primary or idiopathic. However, a lymphoproliferative bone marrow disorder can be demonstrated by flow cytometry in 90% and by histology in approximately 75% of these patients, characterized by clonal proliferation of CD20+,κ+ B-cells 1,4,5. The histological features are those of lymphoplasmacytic lymphoma in about 50% of the patients 1.

Many standard therapies used in other autoimmune diseases or indolent lymphomas are inefficient, e.g. corticosteroids, alkylating agents, interferon-α and, probably, purine analogue single agent therapy 1,6-8. Treatment with the chimeric monoclonal anti-CD20 antibody rituximab has been shown in prospective studies to induce remission in more than half of patients 9,10. Almost all responses were partial, however, and the median response duration was less than one year. Further studies are warranted, therefore, in order to explore the possibilities for increasing the response rate and duration.

The purine analogues, cladribine and fludarabine, are not cyclus dependent, and they have yielded partial response rates of 30-75% and complete response rates of 3-10% in lymphoplasmacytic lymphoma 11,12. Although probably clinically inefficient as monotherapy in most CAD patients, clinical effect of
Sponsor: University of Bergen

Current Primary Outcome:

  • Hemoglobin level
  • Hemolysis
  • Circulatory symptoms
  • Serum monoclonal immunoglobulin level
  • Changes in bone marrow histology
  • Adverse effects


Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: University of Bergen

Dates:
Date Received: September 7, 2006
Date Started: June 2005
Date Completion:
Last Updated: June 18, 2010
Last Verified: June 2010