Therapy for Chronic Cold Agglutinin Disease

NCT00373594 | Completed Phase 2

• 1 other identifier: 911238
• Study Type: interventional
• Target: 30
• Locations: 2 countries
• Sites: 6

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.

Conditions

Cold Agglutinin Disease

Keywords

Cold agglutinin disease; Hemolytic; Anemia; Lymphoproliferative disease; Monoclonal antibodies; Rituximab; Fludarabine

Outcome Measures

Primary Outcomes (6)

• Hemoglobin level

• Hemolysis

• Circulatory symptoms

• Serum monoclonal immunoglobulin level

• Changes in bone marrow histology

• Adverse effects

Interventions

Rituximab DRUG

Fludarabine DRUG

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• Clinical symptoms requiring treatment, such as anaemia or Raynaud-like symptoms
• Informed consent

You may not qualify if:

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

Sponsors & Collaborators

• University of Bergen: lead

Study Sites (6)

Haukeland University Hospital

Bergen, Norway

Location

Haugesund Hospital

Haugesund, Norway

Location

Ullevaal University Hospital

Oslo, 0407, Norway

Location

Rikshospitalet-Radiumhospitalet University Hospital

Oslo, Norway

Location

Sykehuset i Vestfold

Tønsberg, Norway

Location

BMT Clinic, St Petersburg Pavlov State Medical University

Saint Petersburg, 197089, Russia

Location

Related Publications (2)

• 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.

  BACKGROUND

• Berentsen S, Randen U, Vagan AM, Hjorth-Hansen H, Vik A, Dalgaard J, Jacobsen EM, Thoresen AS, Beiske K, Tjonnfjord GE. High response rate and durable remissions following fludarabine and rituximab combination therapy for chronic cold agglutinin disease. Blood. 2010 Oct 28;116(17):3180-4. doi: 10.1182/blood-2010-06-288647. Epub 2010 Jul 15.

  PMID: 20634373 DERIVED

MeSH Terms

Conditions

Anemia, Hemolytic, Autoimmune; Hemolysis; Anemia; Lymphoproliferative Disorders

Interventions

Rituximab; fludarabine

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Hematologic Diseases; Hemic and Lymphatic Diseases; Autoimmune Diseases; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphatic Diseases; Immunoproliferative Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• 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

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 7, 2006
• First Posted: September 8, 2006
• Study Start: June 1, 2005
• Primary Completion: April 1, 2010
• Study Completion: May 1, 2010
• Last Updated: June 22, 2010

Record last verified: 2010-06

Locations

NO (5); RU (1)