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

Phase 2

Completed

• Conditions: Refractory Cold Agglutinin Disease
• Interventions: Drug: Bortezomib

• Registration Number: NCT01696474
• Lead Sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto

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.

Study Timeline

• Study First Submitted: 2012-09-27
• Study First Submitted QC: 2012-09-27
• Study First Posted: 2012-10-01
• Study Start: 2012-12
• Primary Completion: 2017-03-27
• Study Completion: 2017-03-27
• Status Verified: 2017-10
• Last Update Submitted: 2017-10-26
• Last Update Posted: 2017-10-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Bortezomib therapy	Bortezomib	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 Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (8)

Cattedra di Ematologia CTMO Università degli Studi di Parma; 🇮🇹 Parma, Italy

Azienda Ospedaliera Bianchi Melacrino Morelli; 🇮🇹 Reggio Calabria, Italy

Ospedale San Bortolo; 🇮🇹 Vicenza, Italy

Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia; 🇮🇹 Roma, Italy

U.O. Ematologia Clinica - Azienda USL di Pescara; 🇮🇹 Pescara, Italy

Clinica Ematologica - Policlinico Universitario; 🇮🇹 Udine, Italy

Centro Trapianti di Midollo - IRCCS Ospedale Maggiore Policlinico; 🇮🇹 Milano, Italy

Struttura Complessa di Ematologia Ospedali Riuniti Foggia - Azienda Ospedaliero-Universitaria; 🇮🇹 Foggia, Italy