Short Course of Bortezomib in Anemic Patients With Refractory Cold Agglutinin Disease

Refractory Cold Agglutinin Disease Clinical Trial

— CAD0111  

Official title:

Short Course of Bortezomib in Anemic Patients With Refractory Cold Agglutinin Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01696474
• Other study ID #: CAD0111
• Secondary ID: EudraCT number 2
• Status: Completed
• Phase: Phase 2
• First received: September 27, 2012
• Last updated: October 26, 2017
• Start date: December 2012
• Est. completion date: March 27, 2017

Study information

• Verified date: October 2017
• Source: Gruppo Italiano Malattie EMatologiche dell'Adulto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: March 27, 2017
• Est. primary completion date: March 27, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Anemia, Hemolytic, Autoimmune
• Refractory Cold Agglutinin Disease

Intervention

Drug:
• Bortezomib

Locations

Country	Name	City	State
Italy	Struttura Complessa di Ematologia Ospedali Riuniti Foggia - Azienda Ospedaliero-Universitaria	Foggia
Italy	Centro Trapianti di Midollo - IRCCS Ospedale Maggiore Policlinico	Milano
Italy	Cattedra di Ematologia CTMO Università degli Studi di Parma	Parma
Italy	U.O. Ematologia Clinica - Azienda USL di Pescara	Pescara
Italy	Azienda Ospedaliera Bianchi Melacrino Morelli	Reggio Calabria
Italy	Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia	Roma
Italy	Clinica Ematologica - Policlinico Universitario	Udine
Italy	Ospedale San Bortolo	Vicenza

Sponsors (1)

Lead Sponsor	Collaborator
Gruppo Italiano Malattie EMatologiche dell'Adulto

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients who become transfusion-free after Bortezomib therapy.	Cumulative proportion of patients transfusion-free at three months after Bortezomib therapy.	After 3 months from study entry.
Primary	Number of patients who have never been transfused with a >2g hemoglobin rise compared to baseline.		After 3 months from study entry.
Secondary	Number of CTC grade 3 and 4 adverse events.	Evaluation of the incidence of CTC grade 3 and 4 adverse events during and after treatment.	After 12 months from study entry.
Secondary	Duration in months of transfusion independence.		At 12 months from study entry.
Secondary	Effect of treatment on the underlying clonal B cell disorder.		At 3 months from study entry.