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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gruppo Italiano Malattie EMatologiche dell'Adulto
ClinicalTrials.gov Identifier:
NCT01696474
First received: September 27, 2012
Last updated: July 14, 2016
Last verified: July 2016
  Purpose
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 Intervention Phase
Refractory Cold Agglutinin Disease
Drug: Bortezomib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Short Course of Bortezomib in Anemic Patients With Refractory Cold Agglutinin Disease

Resource links provided by NLM:


Further study details as provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:

Primary Outcome Measures:
  • Number of patients who become transfusion-free after Bortezomib therapy. [ Time Frame: After 3 months from study entry. ] [ Designated as safety issue: No ]
    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. [ Time Frame: After 3 months from study entry. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of CTC grade 3 and 4 adverse events. [ Time Frame: After 12 months from study entry. ] [ Designated as safety issue: Yes ]
    Evaluation of the incidence of CTC grade 3 and 4 adverse events during and after treatment.

  • Duration in months of transfusion independence. [ Time Frame: At 12 months from study entry. ] [ Designated as safety issue: No ]
  • Effect of treatment on the underlying clonal B cell disorder. [ Time Frame: At 3 months from study entry. ] [ Designated as safety issue: No ]

Enrollment: 25
Study Start Date: December 2012
Estimated Study Completion Date: December 2016
Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.
  Eligibility

Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Genders Eligible for Study:   Both
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;
  • Cold agglutinin (CA) titer at 4°C of 64 or higher;
  • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01696474

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     History of Changes
Other Study ID Numbers: CAD0111  EudraCT number 2011-006329-42 
Study First Received: September 27, 2012
Last Updated: July 14, 2016
Health Authority: Italy: Ethics Committee
Individual Participant Data  
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
Agglutinins
Cold agglutinins
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Hemagglutinins

ClinicalTrials.gov processed this record on August 25, 2016