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

Primary Purpose

Refractory Cold Agglutinin Disease

Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Bortezomib
Sponsored by
Gruppo Italiano Malattie EMatologiche dell'Adulto
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Refractory Cold Agglutinin Disease focused on measuring Refractory cold agglutinin disease, Bortezomib, blood-transfusion

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

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

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Bortezomib therapy

Arm Description

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.

Outcomes

Primary Outcome Measures

Number of patients who become transfusion-free after Bortezomib therapy.
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.

Secondary Outcome Measures

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.
Duration in months of transfusion independence.
Effect of treatment on the underlying clonal B cell disorder.

Full Information

First Posted
September 27, 2012
Last Updated
October 26, 2017
Sponsor
Gruppo Italiano Malattie EMatologiche dell'Adulto
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1. Study Identification

Unique Protocol Identification Number
NCT01696474
Brief Title
Short Course of Bortezomib in Anemic Patients With Refractory Cold Agglutinin Disease
Acronym
CAD0111
Official Title
Short Course of Bortezomib in Anemic Patients With Refractory Cold Agglutinin Disease
Study Type
Interventional

2. Study Status

Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
December 2012 (undefined)
Primary Completion Date
March 27, 2017 (Actual)
Study Completion Date
March 27, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gruppo Italiano Malattie EMatologiche dell'Adulto

4. Oversight

Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Refractory Cold Agglutinin Disease
Keywords
Refractory cold agglutinin disease, Bortezomib, blood-transfusion

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Bortezomib therapy
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Bortezomib
Primary Outcome Measure Information:
Title
Number of patients who become transfusion-free after Bortezomib therapy.
Description
Cumulative proportion of patients transfusion-free at three months after Bortezomib therapy.
Time Frame
After 3 months from study entry.
Title
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 Measure Information:
Title
Number of CTC grade 3 and 4 adverse events.
Description
Evaluation of the incidence of CTC grade 3 and 4 adverse events during and after treatment.
Time Frame
After 12 months from study entry.
Title
Duration in months of transfusion independence.
Time Frame
At 12 months from study entry.
Title
Effect of treatment on the underlying clonal B cell disorder.
Time Frame
At 3 months from study entry.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Giuseppe Rossi, Dr.
Organizational Affiliation
S.C. Ematologia e Dipartimento di Oncologia Medica Spedali Civili - Brescia
Official's Role
Principal Investigator
Facility Information:
Facility Name
Struttura Complessa di Ematologia Ospedali Riuniti Foggia - Azienda Ospedaliero-Universitaria
City
Foggia
Country
Italy
Facility Name
Centro Trapianti di Midollo - IRCCS Ospedale Maggiore Policlinico
City
Milano
Country
Italy
Facility Name
Cattedra di Ematologia CTMO Università degli Studi di Parma
City
Parma
Country
Italy
Facility Name
U.O. Ematologia Clinica - Azienda USL di Pescara
City
Pescara
Country
Italy
Facility Name
Azienda Ospedaliera Bianchi Melacrino Morelli
City
Reggio Calabria
ZIP/Postal Code
89100
Country
Italy
Facility Name
Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia
City
Roma
Country
Italy
Facility Name
Clinica Ematologica - Policlinico Universitario
City
Udine
Country
Italy
Facility Name
Ospedale San Bortolo
City
Vicenza
ZIP/Postal Code
36100
Country
Italy

12. IPD Sharing Statement

Plan to Share IPD
No

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

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