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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Gruppo Italiano Malattie EMatologiche dell'Adulto
Sponsor:
Information provided by (Responsible Party):
Gruppo Italiano Malattie EMatologiche dell'Adulto
ClinicalTrials.gov Identifier:
NCT01696474
First received: September 27, 2012
Last updated: January 30, 2014
Last verified: January 2014
  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 ]

Estimated Enrollment: 25
Study Start Date: December 2012
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: March 2014 (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 and older
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

Contacts
Contact: Paola Fazi, Dr. p.fazi@gimema.it
Contact: Enrico Crea e.crea@gimema.it

Locations
Italy
S.O.C. di Ematologia - Azienda Ospedaliera - SS. Antonio e Biagio e Cesare Arrigo Recruiting
Alessandria, Italy
Contact: Flavia Salvi, Dr.         
Principal Investigator: Flavia Salvi, Dr.         
Sub-Investigator: Silvia Baraldi, Dr.         
Sezione di Ematologia e Trapianti Spedali Civili Recruiting
Brescia, Italy, 21125
Contact: Erika BORLENGHI, Dr.       erika.ok@libero.it   
Principal Investigator: Erika BORLENGHI, Dr.         
US Dipartimentale Centro per le Malattie del Sangue Not yet recruiting
Castelfranco Veneto, Italy
Contact: Ercole DE BIASI         
Azienda Ospedaliera di Firenze Not yet recruiting
Firenze, Italy, 50011
Contact: Alberto BOSI, Pr.         
Principal Investigator: Alberto BOSI, Pr.         
Struttura Complessa di Ematologia Ospedali Riuniti Foggia - Azienda Ospedaliero-Universitaria Not yet recruiting
Foggia, Italy
Contact: Silvana Franca Capalbo, Dr.         
Principal Investigator: Silvana Franca Capalbo, MD         
Sub-Investigator: Giuseppina Spinosa, Pr.         
Divisione di Ematologia Ospedale "Santa Maria Goretti" Not yet recruiting
Latina, Italy
Contact: Angelo De Blasio, Dr.         
Principal Investigator: Angelo De Blasio, Dr.         
Sub-Investigator: Patrizia Bernuzzi, Dr.         
Azienda Ospedaliera San Paolo - Unità di Ematologia e Trombosi Not yet recruiting
Milano, Italy
Contact: Marco Cattaneo, Pr.         
Principal Investigator: Marco Cattaneo, Pr.         
Centro Trapianti di Midollo - IRCCS Ospedale Maggiore Policlinico Recruiting
Milano, Italy
Contact: Agostino CORTELEZZI, Pr.         
Principal Investigator: Agostino CORTELEZZI, Pr.         
Principal Investigator: Giuseppe GRITTI, Dr.         
Azienda ospedaliera S. Gerardo di Monza Not yet recruiting
Monza, Italy
Contact: Enrico Maria POGLIANI, Pr.         
Principal Investigator: Enrico Maria POGLIANI, Pr.         
S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro Not yet recruiting
Novara, Italy
Contact: Gianluca GAIDANO, Dr.         
Contact: Monia LUNGHI, Dr.         
Principal Investigator: Gianluca GAIDANO, Pr.         
Sub-Investigator: Monia LUNGHI, Dr.         
Divisione di Ematologia con trapianto di midollo - A.U. Policlinico "Paolo Giaccone" Not yet recruiting
Palermo, Italy
Contact: Gerlando Quintini, Dr.         
Principal Investigator: Gerlando Quintini, Dr.         
Sub-Investigator: Cinzia Maugeri, Dr.         
Cattedra di Ematologia CTMO Università degli Studi di Parma Not yet recruiting
Parma, Italy
Contact: Cecilia Caramatti, Dr.         
Principal Investigator: Cecilia Caramatti, Dr.         
Sub-Investigator: Elena Rossetti, Dr.         
Div. di Ematologia IRCCS Policlinico S. Matteo Not yet recruiting
Pavia, Italy, 27100
Contact: Carlo CASTAGNOLA, Dr.         
Contact: Patrizia ZAPPASODI, Dr.         
Principal Investigator: Carlo CASTAGNOLA, Dr.         
Sub-Investigator: Patrizia ZAPPASODI, Dr.         
U.O. Ematologia Clinica - Azienda USL di Pescara Recruiting
Pescara, Italy
Contact: Giuseppe Fioritoni, Pr.         
Principal Investigator: Giuseppe Fioritoni, Pr.         
Sub-Investigator: Antonella Sau, Dr.         
Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale di Piacenza Recruiting
Piacenza, Italy
Contact: Luigi Cavanna, Dr.         
Principal Investigator: Luigi Cavanna, Dr.         
Azienda Ospedaliera Bianchi Melacrino Morelli Not yet recruiting
Reggio Calabria, Italy, 89100
Contact: Maura Brugiatelli, MD    39-965-397-111    mbrugiat@tiscalinet.it   
Unità Operativa Complessa di Ematologia - Arcispedale S. Maria Nuova Not yet recruiting
Reggio Emilia, Italy
Contact: Francesco Merli, Dr.         
Principal Investigator: Francesco Merli, Dr.         
Sub-Investigator: Annalisa Imovili, Dr.         
UO di Ematologia Centro Oncologico Basilicata Not yet recruiting
Rionero in Vulture, Italy
Contact: Pellegrino Musto, Dr.         
Principal Investigator: Pellegrino Musto, Dr.         
Sub-Investigator: Giuseppe Pietrantuono, Dr.         
Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore Not yet recruiting
Rome, Italy, 00168
Contact: Giuseppe Leone, Pr.         
Principal Investigator: Giuseppe LEONI, Pr.         
Sub-Investigator: Luca LAURENTI, Dr.         
Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza Not yet recruiting
S. G. Rotondo, Italy
Contact: Nicola Cascavila, Pr.       n.cascavilla@operapadrepio.it   
Principal Investigator: Nicola Cascavilla, Pr.         
Principal Investigator: Lorella Melillo, Dr.         
SCDO Ematologia 2 AOU S.Giovanni Battista Not yet recruiting
Torino, Italy
Contact: Filippo MARMONT, Dr.         
Principal Investigator: Filippo MARMONT, Dr.         
Sub-Investigator: Ernesta AUDISIO, Dr.         
Azienda U.L.S.S.9 - U.O. di Ematologia Not yet recruiting
Treviso, Italy
Contact: Filippo Gherlinzoni, Pr.         
Principal Investigator: Filippo Gherlinzoni, Pr.         
Sub-Investigator: Michele Gottardi, Dr.         
Clinica Ematologica - Policlinico Universitario Recruiting
Udine, Italy
Contact: Anna Candoni, Dr.         
Principal Investigator: Francesco Zaja, Dr.         
Sub-Investigator: Simona Puglisi, Dr.         
Policlinico G. B. Rossi - Borgo Roma Not yet recruiting
Verona, Italy, 37134
Contact: Giovanni Pizzolo, MD       giovanni.pizzolo@univr.it   
Principal Investigator: Giovanni PIZZOLO, Pr.         
Sub-Investigator: Dino DE VENERI, Dr.         
Ospedale San Bortolo Not yet recruiting
Vicenza, Italy, 36100
Contact: Eros DI BONA, Pr.       dibona@hemato.ven.it   
Principal Investigator: Eros DI BONA, Pr.         
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

No publications provided

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: January 30, 2014
Health Authority: Italy: Ethics Committee

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
Agglutinins
Cold agglutinins
Bortezomib
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Hemagglutinins
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014