Clinical trial NCT01696474: Short Course of Bortezomib in Anemic Patients With Refractory Cold Agglutinin Disease
Official title: Short Course of Bortezomib in Anemic Patients With Refractory Cold Agglutinin Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Refractory Cold Agglutinin Disease
Keywords: Refractory cold agglutinin disease
Bortezomib
blood-transfusion
Lead sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto
Sponsor class: OTHER
First posted: 2012-10-01
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Number of patients who become transfusion-free after Bortezomib therapy.
timeFrame: After 3 months from study entry.
measure: Number of patients who have never been transfused with a >2g hemoglobin rise compared to baseline.
timeFrame: After 3 months from study entry.
Secondary outcomes:
measure: Number of CTC grade 3 and 4 adverse events.
timeFrame: After 12 months from study entry.
measure: Duration in months of transfusion independence.
timeFrame: At 12 months from study entry.
measure: Effect of treatment on the underlying clonal B cell disorder.
timeFrame: At 3 months from study entry.
Other outcomes:
Locations:
city: Foggia
country: Italy
facility: Struttura Complessa di Ematologia Ospedali Riuniti Foggia - Azienda Ospedaliero-Universitaria
city: Milano
country: Italy
facility: Centro Trapianti di Midollo - IRCCS Ospedale Maggiore Policlinico
city: Parma
country: Italy
facility: Cattedra di Ematologia CTMO Università degli Studi di Parma
city: Pescara
country: Italy
facility: U.O. Ematologia Clinica - Azienda USL di Pescara
city: Reggio Calabria
country: Italy
facility: Azienda Ospedaliera Bianchi Melacrino Morelli
city: Roma
country: Italy
facility: Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia
city: Udine
country: Italy
facility: Clinica Ematologica - Policlinico Universitario
city: Vicenza
country: Italy
facility: Ospedale San Bortolo
Study officials:
affiliation: S.C. Ematologia e Dipartimento di Oncologia Medica Spedali Civili - Brescia
name: Giuseppe Rossi, Dr.
role: PRINCIPAL_INVESTIGATOR
References: