Short Course of Bortezomib in Anemic Patients With Refractory Cold Agglutinin Disease (CAD0111)

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.

Study Overview

• Status: Completed
• Conditions: Refractory Cold Agglutinin Disease
• Intervention / Treatment: Drug: Bortezomib

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 Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Foggia, Italy
    • Struttura Complessa di Ematologia Ospedali Riuniti Foggia - Azienda Ospedaliero-Universitaria
  • Milano, Italy
    • Centro Trapianti di Midollo - IRCCS Ospedale Maggiore Policlinico
  • Parma, Italy
    • Cattedra di Ematologia CTMO Università degli Studi di Parma
  • Pescara, Italy
    • U.O. Ematologia Clinica - Azienda USL di Pescara
  • Reggio Calabria, Italy, 89100
    • Azienda Ospedaliera Bianchi Melacrino Morelli
  • Roma, Italy
    • Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia
  • Udine, Italy
    • Clinica Ematologica - Policlinico Universitario
  • Vicenza, Italy, 36100
    • Ospedale San Bortolo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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.	Drug: Bortezomib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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

Outcome Measure	Measure Description	Time Frame
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.
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.

Collaborators and Investigators

• Sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto
• Investigators: Principal Investigator: Giuseppe Rossi, Dr., S.C. Ematologia e Dipartimento di Oncologia Medica Spedali Civili - Brescia

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (ACTUAL): March 27, 2017
• Study Completion (ACTUAL): March 27, 2017

Study Registration Dates

• First Submitted: September 27, 2012
• First Submitted That Met QC Criteria: September 27, 2012
• First Posted (ESTIMATE): October 1, 2012

Study Record Updates

• Last Update Posted (ACTUAL): October 27, 2017
• Last Update Submitted That Met QC Criteria: October 26, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Bortezomib; Refractory cold agglutinin disease; blood-transfusion
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Anemia; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune; Antineoplastic Agents; Bortezomib
• Other Study ID Numbers: CAD0111; EudraCT number 2011-006329-42

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO