This trial is active, not recruiting.

Condition refractory cold agglutinin disease
Treatment bortezomib
Phase phase 2
Target proteasome
Sponsor Gruppo Italiano Malattie EMatologiche dell'Adulto
Start date December 2012
End date March 2016
Trial size 25 participants
Trial identifier NCT01696474, CAD0111, EudraCT number 2011-006329-42


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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
A single course of Bortezomib will be given at the dose of 1,3 mg/sqm iv on days 1, 4, 8, 11. Prophylaxis of HZ reactivation will be given with oral acyclovir at the dosage of 400 mg twice daily for one month after the end of Bortezomib.

Primary Outcomes

Number of patients who become transfusion-free after Bortezomib therapy.
time frame: After 3 months from study entry.
Number of patients who have never been transfused with a >2g hemoglobin rise compared to baseline.
time frame: After 3 months from study entry.

Secondary Outcomes

Number of CTC grade 3 and 4 adverse events.
time frame: After 12 months from study entry.
Duration in months of transfusion independence.
time frame: At 12 months from study entry.
Effect of treatment on the underlying clonal B cell disorder.
time frame: At 3 months from study entry.

Eligibility Criteria

Male or female participants from 18 years up to 99 years old.

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; - Cold agglutinin (CA) titer at 4°C of 64 or higher; - 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.

Additional Information

Official title Short Course of Bortezomib in Anemic Patients With Refractory Cold Agglutinin Disease
Principal investigator Giuseppe Rossi, Dr.
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.
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by Gruppo Italiano Malattie EMatologiche dell'Adulto.