Refractory Cold Agglutinin DiseasePhase 2CAD0111NCT01696474
Short Course of Bortezomib in Anemic Patients With Refractory Cold Agglutinin Disease
A Phase 2 study testing Bortezomib in people with Refractory Cold Agglutinin Disease, run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 8 sites in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Refractory Cold Agglutinin Disease
- What is being tested?
- Bortezomib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 8 sitesItaly
- Study dates
- Dec 2012to 27 Mar 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
Italy8 sites
Struttura Complessa di Ematologia Ospedali Riuniti Foggia - Azienda Ospedaliero-Universitaria
Foggia
Centro Trapianti di Midollo - IRCCS Ospedale Maggiore Policlinico
Milan
Cattedra di Ematologia CTMO Università degli Studi di Parma
Parma
U.O. Ematologia Clinica - Azienda USL di Pescara
Pescara
Azienda Ospedaliera Bianchi Melacrino Morelli
Reggio Calabria, 89100
Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia
Roma
Clinica Ematologica - Policlinico Universitario
Udine
Ospedale San Bortolo
Vicenza, 36100
About this study
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.
Read the 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.
- Conditions
- Refractory Cold Agglutinin Disease
- Being tested
- Bortezomib
- Keywords
- Refractory cold agglutinin disease, Bortezomib, blood-transfusion
- Medical subject headings
- Anemia, Hemolytic, Autoimmune
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BortezomibDrug
| Study group | Role | What they receive |
|---|---|---|
| Bortezomib therapy | Experimental | 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. Receives: Drug: Bortezomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients who become transfusion-free after Bortezomib therapy.
Cumulative proportion of patients transfusion-free at three months after Bortezomib therapy.
Measured: After 3 months from study entry.
Number of patients who have never been transfused with a >2g hemoglobin rise compared to baseline.
Measured: After 3 months from study entry.
Secondary outcomes (3)
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.
Measured: After 12 months from study entry.
Duration in months of transfusion independence.
Measured: At 12 months from study entry.
Effect of treatment on the underlying clonal B cell disorder.
Measured: At 3 months from study entry.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2012 (estimated)
- Study startDec 2012
- Primary completion27 Mar 2017
- Study completion27 Mar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory Cold Agglutinin DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gruppo Italiano Malattie EMatologiche dell'Adulto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Giuseppe Rossi, Dr., Principal investigator, S.C. Ematologia e Dipartimento di Oncologia Medica Spedali Civili - Brescia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01696474
- Sponsor's protocol ID
- CAD0111
- Other IDs
- EudraCT number 2011-006329-42
- Acronym
- CAD0111
- Status last verified
- Oct 2017
- First submitted
- 27 Sep 2012
- Last updated
- 27 Oct 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Short Course of Bortezomib in Anemic Patients With Refractory Cold Agglutinin Disease
- ClinicalTrials.gov ID
- NCT01696474
- Acronym / sponsor ID
- CAD0111 / CAD0111
- Conditions
- Refractory Cold Agglutinin Disease
- Keywords
- Refractory cold agglutinin disease, Bortezomib, blood-transfusion
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Gruppo Italiano Malattie EMatologiche dell'AdultoUniversity, hospital or other
- Study start
- Dec 2012
- Primary completion
- 27 Mar 2017 (actual)
- Study completion
- 27 Mar 2017 (actual)
- First posted
- 1 Oct 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bortezomib therapy | Experimental | Drug: BortezomibA 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (6 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bortezomib | Drug | Bortezomib therapy |
Primary outcome
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.
Number of patients who have never been transfused with a >2g hemoglobin rise compared to baseline.
Time frame: After 3 months from study entry.
3 secondary outcomes
Number of CTC grade 3 and 4 adverse events.
Time frame: After 12 months from study entry.
Duration in months of transfusion independence.
Time frame: At 12 months from study entry.
Effect of treatment on the underlying clonal B cell disorder.
Time frame: At 3 months from study entry.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2017.
- Individual participant dataSharing planned: No
Related trials for Refractory Cold Agglutinin Disease
Not yet recruiting
A Multicenter Prospective Study of Iptacopan in the Treatment of Refractory/Relapsed Autoimmune Hemolytic Anemia (AIHA)
AIHA - Warm Autoimmune Hemolytic Anemia, AIHA - Cold Autoimmune Hemolytic Anemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Giuseppe Rossi, Dr. principal investigator
S.C. Ematologia e Dipartimento di Oncologia Medica Spedali Civili - Brescia
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bortezomib in people with Refractory Cold Agglutinin Disease, run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 8 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients who become transfusion-free after Bortezomib therapy. (time frame: After 3 months from study entry.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2017.