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

• ClinicalTrials.gov Identifier: NCT01696474
• Recruitment Status: Completed
• First Posted: October 1, 2012
• Last Update Posted: October 27, 2017
• Sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto
• Information provided by (Responsible Party): Gruppo Italiano Malattie EMatologiche dell'Adulto

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Refractory Cold Agglutinin Disease	Drug: Bortezomib	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Short Course of Bortezomib in Anemic Patients With Refractory Cold Agglutinin Disease
• Study Start Date: December 2012
• Actual Primary Completion Date: March 27, 2017
• Actual Study Completion Date: March 27, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Number of patients who become transfusion-free after Bortezomib therapy. [ Time Frame: After 3 months from study entry. ]
   Cumulative proportion of patients transfusion-free at three months after Bortezomib therapy.
2. 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 Outcome Measures :

1. Number of CTC grade 3 and 4 adverse events. [ Time Frame: After 12 months from study entry. ]
   Evaluation of the incidence of CTC grade 3 and 4 adverse events during and after treatment.
2. Duration in months of transfusion independence. [ Time Frame: At 12 months from study entry. ]
3. Effect of treatment on the underlying clonal B cell disorder. [ Time Frame: At 3 months from study entry. ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

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, 89100

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, 36100

Sponsors and Collaborators

Gruppo Italiano Malattie EMatologiche dell'Adulto

Investigators

• Principal Investigator: Giuseppe Rossi, Dr.; S.C. Ematologia e Dipartimento di Oncologia Medica Spedali Civili - Brescia

More Information

• Responsible Party: Gruppo Italiano Malattie EMatologiche dell'Adulto
• ClinicalTrials.gov Identifier: NCT01696474
• Other Study ID Numbers: CAD0111; EudraCT number 2011-006329-42
• First Posted: October 1, 2012
• Last Update Posted: October 27, 2017
• Last Verified: October 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:

Refractory cold agglutinin disease; Bortezomib; blood-transfusion

Additional relevant MeSH terms:

Anemia, Hemolytic, Autoimmune; Anemia, Hemolytic; Anemia; Hematologic Diseases; Autoimmune Diseases; Immune System Diseases; Bortezomib; Antineoplastic Agents