Refractory Cold Agglutinin Disease
Conditions
Keywords
Refractory cold agglutinin disease, Bortezomib, blood-transfusion
Brief summary
This multicenter, phase II, open label study will enroll patients with chronic cold agglutinin disorder. A single course of Bortezomib will be given at the dose of 1,3 mg/sqm iv on days 1, 4, 8, 11.
Detailed description
Based on its activity in MM, single agent Bortezomib was tested in phase II trials in lymphoplasmacytic lymphoma, the disorder most frequently associated with CAD, and achieved 40-80% responses. These striking clinical responses indicate that proteasome activity is critical for the survival of immunoglobulin-secreting cells. The resolution of transfusion requirement in two patients with refractory CAD associated with IgMk monoclonal gammopathy has been reported after treatment with a short course of Bortezomib. It may be interesting to test the efficacy of Bortezomib in a larger series of patients with refractory CAD, idiopathic or associated with an otherwise asymptomatic B cell clonal disorder, and to evaluate the duration of clinical benefit.
Interventions
DRUGBortezomib
Sponsors
Gruppo Italiano Malattie EMatologiche dell'Adulto
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with chronic cold agglutinin disorder requiring or with a hemoglobin concentration below 10g/L determined at least monthly during the two months before entering the trial; * Failure of at least one previous treatment attempt; * Hemoglobin level assessment; * Presence of serum cold agglutinin (CA). If an overnight incubation is used for CA detection, a titer at 4°C of 64 or higher is required; * Written informed consent.
Exclusion criteria
* Presence of a concomitant lymphoproliferative disorder requiring specific treatment for reasons other than cold agglutinin related hemolytic anemia; * Preexisting peripheral neuropathy; * Known hypersensitivity to Bortezomib; * Non-cooperative behaviour or non-compliance; * Psychiatric diseases or conditions that might impair the ability to give informed consent; * Patients who are pregnant (women of childbearing potential must have a negative serum pregnancy test). Post-menopausal women must be amenorrhoic for at least 24 months to be considered of non-childbearing potential. Male and female patients must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients who become transfusion-free after Bortezomib therapy. | After 3 months from study entry. | Cumulative proportion of patients transfusion-free at three months after Bortezomib therapy. |
| Number of patients who have never been transfused with a >2g hemoglobin rise compared to baseline. | After 3 months from study entry. | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of CTC grade 3 and 4 adverse events. | After 12 months from study entry. | Evaluation of the incidence of CTC grade 3 and 4 adverse events during and after treatment. |
| Duration in months of transfusion independence. | At 12 months from study entry. | — |
| Effect of treatment on the underlying clonal B cell disorder. | At 3 months from study entry. | — |
Countries
Italy
Outcome results
None listed