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

NCT ID: NCT01696474

Last Updated: 2017-10-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2017-03-27

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.

Conditions

Refractory Cold Agglutinin Disease

Keywords

Refractory cold agglutinin disease; Bortezomib; blood-transfusion

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bortezomib therapy

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.

Group Type: EXPERIMENTAL

Bortezomib

Intervention Type: DRUG

Interventions

Bortezomib

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gruppo Italiano Malattie EMatologiche dell'Adulto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Giuseppe Rossi, Dr.

Role: PRINCIPAL_INVESTIGATOR

S.C. Ematologia e Dipartimento di Oncologia Medica Spedali Civili - Brescia

Locations

Struttura Complessa di Ematologia Ospedali Riuniti Foggia - Azienda Ospedaliero-Universitaria

Foggia, , Italy

Centro Trapianti di Midollo - IRCCS Ospedale Maggiore Policlinico

Milan, , 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, , Italy

Countries

Italy

Other Identifiers

EudraCT number 2011-006329-42

Identifier Type: -

Identifier Source: secondary_id

CAD0111

Identifier Type: -

Identifier Source: org_study_id