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Therapy for Chronic Cold Agglutinin Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00373594
Recruitment Status : Completed
First Posted : September 8, 2006
Last Update Posted : June 22, 2010
Information provided by:
University of Bergen

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.

Condition or disease Intervention/treatment Phase
Cold Agglutinin Disease Drug: Rituximab Drug: Fludarabine Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Fludarabine.
Study Start Date : June 2005
Actual Primary Completion Date : April 2010
Actual Study Completion Date : May 2010

Primary Outcome Measures :
  1. Hemoglobin level
  2. Hemolysis
  3. Circulatory symptoms
  4. Serum monoclonal immunoglobulin level
  5. Changes in bone marrow histology
  6. Adverse effects

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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. CAD diagnosis defined by the combination of:

    • Chronic haemolysis
    • Cold agglutinin titre > 64
    • Positive direct antiglobulin test when performed with polyspecific antiserum, negative (or only weakly positive) with anti-IgG, and strongly positive with anti-C3d
  2. The presence of a clonal B-cell lymphoproliferative disorder defined by:

    • Monoclonal IgMκ band by serum electrophoresis and immunofixation, and
    • Lymphocyte phenotype with κ/λ-ratio > 3.5 and CD20+,κ+ co-expression, using flowcytometric immunophenotyping of bone marrow aspirates
  3. Clinical symptoms requiring treatment, such as anaemia or Raynaud-like symptoms
  4. Informed consent

Exclusion Criteria:

  1. An aggressive lymphoma
  2. Blood lymphocyte count > 50 . 109/L
  3. Non-lymphatic malignant disease other than basal cell carcinoma
  4. Contra-indications to rituximab or fludarabine therapy
  5. Inability to cooperate

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00373594

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Haukeland University Hospital
Bergen, Norway
Haugesund Hospital
Haugesund, Norway
Ullevaal University Hospital
Oslo, Norway, 0407
Rikshospitalet-Radiumhospitalet University Hospital
Oslo, Norway
Sykehuset i Vestfold
Tonsberg, Norway
Russian Federation
BMT Clinic, St Petersburg Pavlov State Medical University
St Petersburg, Russian Federation, 197089
Sponsors and Collaborators
University of Bergen
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Study Chair: Sigbjorn Berentsen, MD, PhD Haugesund Hospital and University of Bergen
Study Chair: Geir E Tjonnfjord, MD, PhD Rikshospitalet-Radiumhospitalet University Hospital, Oslo
Study Chair: Elling Ulvestad, MD, PhD The Gade Institute, Haukeland University Hospital, Bergen
1. Berentsen S, Ulvestad E, Langholm R, Beiske K, Hjorth-Hansen H, Ghanima W et al. Primary chronic cold agglutinin disease: a population based clinical study of 86 patients. Haematologica 2006;91:460-6. 2. Ulvestad E, Berentsen S, Bo K, Shammas FV. Clinical immunology of chronic cold agglutinin disease. Eur J Haematol 1999;63:259-66. 3. Ulvestad E, Berentsen S, Mollnes TE. Acute phase haemolysis in chronic cold agglutinin disease. Scand J Immunol 2001;54:239-42. 4.Berentsen S, Ulvestad E, Gjertsen BT, Hjorth-Hansen H, Langholm R, Knutsen H et al. Rituximab for primary chronic cold agglutinin disease: a prospective study of 37 courses of therapy in 27 patients. Blood 2004;103:2925-8.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Dr. S. Berentsen, MD, PhD, Haugesund Hospital
ClinicalTrials.gov Identifier: NCT00373594    
Other Study ID Numbers: 911238
First Posted: September 8, 2006    Key Record Dates
Last Update Posted: June 22, 2010
Last Verified: June 2010
Keywords provided by University of Bergen:
Cold agglutinin disease
Lymphoproliferative disease
Monoclonal antibodies
Additional relevant MeSH terms:
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Anemia, Hemolytic, Autoimmune
Anemia, Hemolytic
Hematologic Diseases
Autoimmune Diseases
Immune System Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents