Bendamustine and Rituximab Combination Therapy for Cold Agglutinin Disease

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT02689986
• Date of registration: 16/02/2016
• Prospective Registration: No
• Primary sponsor: Helse Fonna
• Public title: Bendamustine and Rituximab Combination Therapy for Cold Agglutinin Disease CAD5
• Scientific 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
• Date of first enrolment: January 2013
• Target sample size: 43
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02689986
• Study type: Interventional
• Study design: Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Denmark, Finland, Norway

Contacts

• Name: Geir E Tjonnfjord, MD, PhD
• Affiliation: Oslo University Hospital, Oslo, Norway

• Name: Henrik Birgens, MD, PhD
• Affiliation: Herlev University Hospital, Copenhagen, Denmark

• Name: Sigbjorn Berentsen, MD, PhD
• Affiliation: Department of Research and Innovation, Haugesund Hospital

• Name: Markku Oksman, MD
• Affiliation: Turku University Hospital, Turku, Finland

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Cold Agglutinin Disease

Autoimmune Hemolytic Anemia

Intervention(s)

Drug: Bendamustine, Rituximab

Primary Outcome(s)

Frequency of complete and partial responses (CR/PR) [Time Frame: 6 months]

Secondary Outcome(s)

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

Time to response (TTR) [Time Frame: 6 months]

Response duration [Time Frame: Through study completion; an average of 2 years]

Time to best response (TTBR) [Time Frame: 1 year]

Secondary ID(s)

CAD5

Source(s) of Monetary Support

Please refer to primary and secondary sponsors