Therapy for chronic cold agglutinin disease: A prospective, non-randomized international multicenter trial on the safety and efficacy of bendamustine and rituximab combination therapy.

• Register: EUCTR
• Last refreshed on: 10 January 2022
• Main ID: EUCTR2011-004835-30-NO
• Date of registration: 29/08/2012
• Prospective Registration: Yes
• Primary sponsor: Department of Medicine, Haugesund Hospital
• Public title: Therapy for chronic cold agglutinin disease: A prospective, non-randomized international multicenter trial on the safety and efficacy of bendamustine and rituximab combination therapy.
• Scientific title: Therapy for chronic cold agglutinin disease: A prospective, non-randomized international multicenter trial on the safety and efficacy of bendamustine and rituximab combination therapy. - CAD5
• Date of first enrolment: 23/10/2012
• Target sample size: 50
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-004835-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Denmark, Finland, Norway

Contacts

• Name: Sigbjorn Berentsen
• Affiliation: Department of Medicine

• Name: Sigbjorn Berentsen
• Affiliation: Department of Medicine

Key inclusion & exclusion criteria

Inclusion criteria:
1. CAD diagnosis defined by the combination of –
a. Chronic hemolysis
b. Cold agglutinin titer > 64
c. 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 –
a. Monoclonal band by serum electrophoresis with immunofixation, and/or
b. CD20 positive lymphocyte population with cellular ?/?-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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

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 > 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 < 18 years
10. Inability to cooperate


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Primary chronic cold agglutinin disease requiring treatment

Intervention(s)

Trade Name: Levact
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: BENDAMUSTINE HYDROCHLORIDE
CAS Number: 3543-75-7
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2.5-

Trade Name: MabThera
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Weekly during treatment, monthly during six months after treatment and every third month after that up to three years after end of therapy.

Main Objective: Rate of complete and partial responses, respectively.

Primary end point(s): Rate of complete and partial responses

Secondary Objective: Time to response; time to best response; hematological toxicity grade 4; frequency of dose reduction; response duration.

Secondary Outcome(s)

Secondary end point(s): Time to response;
time to best response;
hematological toxicity grade 4;
frequency of dose reduction;
response duration.

Timepoint(s) of evaluation of this end point: Weekly during treatment, monthly during six months after treatment and every third month after that up to three years after end of therapy.

Secondary ID(s)

CAD5

Source(s) of Monetary Support

norpharma

Mundipharma

Ethics review

Status: Approved
Approval date: 29/02/2012
Contact:

Results

• Results available: Yes
• Date Posted: 22/02/2021
• Date Completed: 22/05/2017
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-004835-30/results