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Bendamustine and Rituximab Combination Therapy for Cold Agglutinin Disease (CAD5)

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ClinicalTrials.gov Identifier: NCT02689986
Recruitment Status : Completed
First Posted : February 24, 2016
Last Update Posted : January 9, 2017
Sponsor:
Information provided by (Responsible Party):
Sigbjorn Berentsen, Helse Fonna

Brief Summary:
Prospective, non-randomized multicenter study on the safety and efficacy of combination therapy with bendamustine and rituximab for chronic cold agglutinin disease.

Condition or disease Intervention/treatment Phase
Cold Agglutinin Disease Autoimmune Hemolytic Anemia Drug: Bendamustine, Rituximab Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 43 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The CAD5 Study::Therapy for Chronic Cold Agglutinin Disease: A Prospective, Non-randomized International Multicenter Trial on the Safety and Efficacy of Bendamustine and Rituximab Combination Therapy
Study Start Date : January 2013
Actual Primary Completion Date : December 2016
Actual Study Completion Date : December 2016


Arm Intervention/treatment
Experimental: Treatment arm
Bendamustine, Rituximab
Drug: Bendamustine, Rituximab
Bendamustine, Rituximab
Other Name: Levact, MabThera




Primary Outcome Measures :
  1. Frequency of complete and partial responses (CR/PR) [ Time Frame: 6 months ]

    Responses will be assessed using the following, previously published definitions:

    Complete response (CR), Absence of anemia, no signs of hemolysis, no clinical symptoms of CAD, undetectable serum monoclonal protein, and no signs of clonal lymphoproliferation by bone marrow histology, immunohistochemistry and flow cytometry.

    Partial response (PR), Stable increase in hemoglobin levels by at least 2.0 g/dL or to the normal range, combined with a reduction of serum IgM concentrations by at least 50% or to the normal range, improvement of clinical symptoms, and transfusion independency.

    Non-response (NR), Patients not meeting the criteria for CR or PR.



Secondary Outcome Measures :
  1. Time to response (TTR) [ Time Frame: 6 months ]
    Time to response (TTR) is the time from start of therapy to the achievement of any degree of response.

  2. Time to best response (TTBR) [ Time Frame: 1 year ]
    Time to best response (TTBR) is the time from start of therapy to the observation of the highest hemoglobin level achieved + 0.5 g/dL.

  3. Response duration [ Time Frame: Through study completion; an average of 2 years ]
    Response duration is the time from achievement of any degree of response to relapse. Relapse is defined by one or more of the following events: A decline in hemoglobin level by at least 2.0 g/dL from the highest level achieved or to below 10.0 g/dL; transfusion requirement; or recurrence of significant cold-induced circulatory symptoms.

  4. Number of participants with treatment-related adverse events as assessed by current CTCAE criteria [ Time Frame: Through study completion; an average of 2 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. CAD diagnosis defined by the combination of -

    1. Chronic hemolysis
    2. Cold agglutinin titer 64 or higher
    3. 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 -

    1. Monoclonal band by serum electrophoresis with immunofixation, and/or
    2. CD20 positive lymphocyte population with cellular kappa/lamda-ratio higher than 3.5 or less than 0.9, using flowcytometric immunophenotyping of bone marrow aspirates
  3. Indication for therapy, i.e. significant anemia and/or considerable cold-induced circulatory symptoms
  4. Written informed consent

Exclusion Criteria:

  1. An aggressive lymphoma
  2. Non-lymphatic malignant disease other than basal cell carcinoma of the skin. A history of probably cured cancer is not an exclusion criterion.
  3. Known HIV infection
  4. Acute or chronic hepatitis B or C
  5. Liver failure or active parenchymal liver disease. Bilirubin levels higher than 51 mol/L (3.0 mg/dL) when due to hepatic impairment. Elevated serum bilirubin level due to hemolysis is not an exclusion criterion.
  6. Pregnancy or breast-feeding
  7. Patients of childbearing age who are not willing to use safe contraception during the entire study period and 6 months following its cessation
  8. All contraindications to the study drugs will be regarded as exclusion criteria.
  9. Age below 18 years
  10. 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): NCT02689986


Locations
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Denmark
Herlev University Hospital
Copenhagen, Denmark
Finland
Turku University Hospital
Turku, Finland
Norway
Haukeland University Hospital
Bergen, Norway, NO-5021
Vestre Viken Hospital
Drammen, Norway, NO-3000
Haugesund Hospital
Haugesund, Norway, NO-5504
Akershus University Hospital
Nordbyhagen, Norway
Oslo University Hospital
Oslo, Norway, NO-0027
St Olav University Hospital
Trondheim, Norway, NO-7006
Sponsors and Collaborators
Helse Fonna
Investigators
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Study Chair: Sigbjorn Berentsen, MD, PhD Department of Research and Innovation, Haugesund Hospital
Principal Investigator: Markku Oksman, MD Turku University Hospital, Turku, Finland
Principal Investigator: Henrik Birgens, MD, PhD Herlev University Hospital, Copenhagen, Denmark
Principal Investigator: Geir E Tjonnfjord, MD, PhD Oslo University Hospital, Oslo, Norway

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Sigbjorn Berentsen, MD, PhD, Helse Fonna
ClinicalTrials.gov Identifier: NCT02689986     History of Changes
Other Study ID Numbers: CAD5
First Posted: February 24, 2016    Key Record Dates
Last Update Posted: January 9, 2017
Last Verified: January 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data are to be shared between authors before final analysis and publication.
Keywords provided by Sigbjorn Berentsen, Helse Fonna:
Cold agglutinin
Cold agglutinin disease
Anemia
Hemolytic
Autoimmune
Bendamustine
Rituximab
Additional relevant MeSH terms:
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Anemia, Hemolytic
Anemia, Hemolytic, Autoimmune
Hemolysis
Anemia
Hematologic Diseases
Pathologic Processes
Autoimmune Diseases
Immune System Diseases
Rituximab
Bendamustine Hydrochloride
Cold agglutinins
Agglutinins
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Hemagglutinins