Primary Amyloidosis of Light Chain TypePhase 2DIACALNCT01531751
High Cut-off Hemodialysis in Patients With Advanced Cardiac AL Amyloidosis and End Stage Renal Disease
A Phase 2 study testing High Cut-off Hemodialysis and Chemotherapy in people with Primary Amyloidosis of Light Chain Type, run by Fondazione IRCCS Policlinico San Matteo di Pavia at 1 site in Italy.
Trial summary
The aim of the study is to assess survival of patients with advanced cardiac AL amyloidosis treated with high cut-off hemodialysis (HCO-HD) combined with chemotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Primary Amyloidosis of Light Chain Type
- What is being tested?
- High Cut-off Hemodialysis and Chemotherapy
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteItaly
- Study dates
- Feb 2015to Dec 2015
- 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of AL amyloidosis.
- Age ≥ 18 years.
- Evidence of a monoclonal light chain in serum and/or urine by positive immunofixation and abnormal FLC κ/λ ratio.
- Evidence of cardiac involvement at echocardiography (mean left ventricular wall thickness > 12 mm in the absence of other causes).
- Cardiac stage III (both NT-proBNP > 332 ng/L and cTnI > 100 ng/L).
- Estimated GFR < 15 mL/min per 1.73 m2 or requiring dialysis.
- NYHA class III or IV.
- Initiation of chemotherapy for AL amyloidosis scheduled between day 3 and day 8 after first HCO-HD session.
Who cannot join
- Non-AL (e.g. familial, senile) amyloidosis.
- Concomitant non-amyloid related clinically significant cardiac diseases.
- Involved (amyloidogenic) FLC < 100 mg/L.
- Inability to undergo chemotherapy for AL amyloidosis.
- Uncontrolled infection.
- Inability to give informed consent.
- Previous or ongoing psychiatric illness (excluding reactive depression).
- Pregnant or nursing women.
Trial locations and contacts
1 site in 1 country.
Italy1 site
Centro per lo Studio e la Cura delle Amiloidosi Sistemiche - Fondazione IRCCS Policlinico S.Matteo
Pavia, 27100
About this study
Official title: An Open Label Phase II Trial of Free Light Chain Removal by Extended High Cut-Off Hemodialysis in Patients With Advanced Cardiac AL Amyloidosis and End-Stage Renal Disease.
The aim of the study is to assess survival of patients with advanced cardiac AL amyloidosis treated with high cut-off hemodialysis (HCO-HD) combined with chemotherapy.
Read the detailed description
This will be a single-center phase II open label trial. Subjects with advanced cardiac AL amyloidosis and end-stage renal disease will undergo HCO-HD while receiving chemotherapy for their plasma cell dyscrasia according to the current standards of care.
After giving written informed consent, the patients will be evaluated for eligibility. Briefly, the subjects with a biopsy-proven diagnosis of AL amyloidosis who are cardiac stage 3 based on NT-proBNP (> 332 ng/L) and cTnI (> 100 ng/L) and whose estimated glomerular filtration rate (eGFR) is < 15 mL/min per 1.73 m2 will be eligible for the study. Patients with non-AL (e.g. familial and senile) amyloidosis will be excluded, as well as subjects who have less than 100 mg/L circulating amyloidogenic FLC. Sixteen patients will be enrolled.
The study includes 3 periods: screening, treatment followed by the end-of-treatment evaluation and follow-up. During dialysis the patients will undergo the first cycle of chemotherapy according to the current standard of care for subjects with advanced cardiac AL amyloidosis. Measurements of FLC and cardiac biomarkers will be done before and after each dialysis session. High cutoff HD will be continued during the first chemotherapy cycle. After the first cycle the end-of-treatment evaluation will take place. Follow-up evaluations will be performed after the end of each subsequent chemotherapy cycle and every 2 months after chemotherapy discontinuation for 1 year or until disease progression occurs.
- Conditions
- Primary Amyloidosis of Light Chain Type
- Being tested
- High Cut-off Hemodialysis, Chemotherapy
- Keywords
- HCO-HD, survival, cardiac biomarkers, AL amyloidosis, Light Chain Amyloidosis
- Medical subject headings
- Immunoglobulin Light-chain Amyloidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High Cut-off HemodialysisDevice
Also called Theralite
During dialysis the patients will undergo the first cycle of chemotherapy according to the current standard of care for subjects with advanced cardiac AL amyloidosis. Measurements of FLC and cardiac biomarkers will be done before and after each dialysis session. High cutoff HD will be continued during the first chemotherapy cycle. After the first cycle the end-of-treatment evaluation will take place.
ChemotherapyDrug
Chemotherapy will be based on alchilators, proteasome inhibitors, steroids, IMiDs.
| Study group | Role | What they receive |
|---|---|---|
| High Cut-off Hemodialysis | Experimental | Not described Receives: Device: High Cut-off Hemodialysis; Drug: Chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival
The primary objective will be to assess survival of patients with advanced cardiac AL amyloidosis treated with HCO-HD combined with chemotherapy.
Measured: 6 months
Secondary outcomes (1)
tolerability of the experimental device
Secondary objectives will be to assess the feasibility and tolerability of HCO-HD in patients with advanced cardiac AL amyloidosis, the efficiency of HCO-HD plus chemotherapy in reducing amyloidogenic FLC in this setting, and the ability of this approach to promote improvement of cardiac dysfunction as assessed by biomarkers.
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2012 (estimated)
- Study startFeb 2015
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Primary Amyloidosis of Light Chain TypeStudies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Policlinico San Matteo di PaviaThe sponsor's other registered studies.
- 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondazione IRCCS Policlinico San Matteo di Pavia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Giampaolo Merlini, Fondazione IRCCS Policlinico San Matteo di Pavia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01531751
- Sponsor's protocol ID
- AC-005-IT
- Acronym
- DIACAL
- Status last verified
- Mar 2018
- First submitted
- 11 Jan 2012
- Last updated
- 21 Mar 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Hutchison CA, Cockwell P, Reid S, Chandler K, Mead GP, Harrison J, Hattersley J, Evans ND, Chappell MJ, Cook M, Goehl H, Storr M, Bradwell AR. Efficient removal of immunoglobulin free light chains by hemodialysis for multiple myeloma: in vitro and in vivo studies. J Am Soc Nephrol. 2007 Mar;18(3):886-95. doi: 10.1681/ASN.2006080821. Epub 2007 Jan 17.
PubMed 17229909
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Phase II Trial of Free Light Chain Removal by Extended High Cut-Off Hemodialysis in Patients With Advanced Cardiac AL Amyloidosis and End-Stage Renal Disease.
- ClinicalTrials.gov ID
- NCT01531751
- Acronym / sponsor ID
- DIACAL / AC-005-IT
- Conditions
- Primary Amyloidosis of Light Chain Type
- Keywords
- HCO-HD, survival, cardiac biomarkers, AL amyloidosis, Light Chain Amyloidosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Fondazione IRCCS Policlinico San Matteo di PaviaUniversity, hospital or other
- Study start
- Feb 2015 (actual)
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 13 Feb 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.
The aim of the study is to assess survival of patients with advanced cardiac AL amyloidosis treated with high cut-off hemodialysis (HCO-HD) combined with chemotherapy.
Detailed description
This will be a single-center phase II open label trial. Subjects with advanced cardiac AL amyloidosis and end-stage renal disease will undergo HCO-HD while receiving chemotherapy for their plasma cell dyscrasia according to the current standards of care.
After giving written informed consent, the patients will be evaluated for eligibility. Briefly, the subjects with a biopsy-proven diagnosis of AL amyloidosis who are cardiac stage 3 based on NT-proBNP (> 332 ng/L) and cTnI (> 100 ng/L) and whose estimated glomerular filtration rate (eGFR) is < 15 mL/min per 1.73 m2 will be eligible for the study. Patients with non-AL (e.g. familial and senile) amyloidosis will be excluded, as well as subjects who have less than 100 mg/L circulating amyloidogenic FLC. Sixteen patients will be enrolled.
The study includes 3 periods: screening, treatment followed by the end-of-treatment evaluation and follow-up. During dialysis the patients will undergo the first cycle of chemotherapy according to the current standard of care for subjects with advanced cardiac AL amyloidosis. Measurements of FLC and cardiac biomarkers will be done before and after each dialysis session. High cutoff HD will be continued during the first chemotherapy cycle. After the first cycle the end-of-treatment evaluation will take place. Follow-up evaluations will be performed after the end of each subsequent chemotherapy cycle and every 2 months after chemotherapy discontinuation for 1 year or until disease progression occurs.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| High Cut-off Hemodialysis | Experimental | Device: High Cut-off Hemodialysis, Drug: Chemotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Diagnosis of AL amyloidosis.
- Age ≥ 18 years.
- Evidence of a monoclonal light chain in serum and/or urine by positive immunofixation and abnormal FLC κ/λ ratio.
- Evidence of cardiac involvement at echocardiography (mean left ventricular wall thickness > 12 mm in the absence of other causes).
- Cardiac stage III (both NT-proBNP > 332 ng/L and cTnI > 100 ng/L).
Key exclusion criteria (8 listed)
- Non-AL (e.g. familial, senile) amyloidosis.
- Concomitant non-amyloid related clinically significant cardiac diseases.
- Involved (amyloidogenic) FLC < 100 mg/L.
- Inability to undergo chemotherapy for AL amyloidosis.
- Uncontrolled infection.
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 |
|---|---|---|
| High Cut-off HemodialysisAlso: TheraliteDuring dialysis the patients will undergo the first cycle of chemotherapy according to the current standard of care for subjects with advanced cardiac AL amyloidosis. Measurements of FLC and cardiac biomarkers will be done before and after each dialysis session. High cutoff HD will be continued during the first chemotherapy cycle. After the first cycle the end-of-treatment evaluation will take place. | Device | High Cut-off Hemodialysis |
| ChemotherapyChemotherapy will be based on alchilators, proteasome inhibitors, steroids, IMiDs. | Drug | High Cut-off Hemodialysis |
Primary outcome
Survival
Time frame: 6 months
The primary objective will be to assess survival of patients with advanced cardiac AL amyloidosis treated with HCO-HD combined with chemotherapy.
1 secondary outcome
tolerability of the experimental device
Time frame: 1 month
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2018.
- Background: PubMed 17229909Hutchison CA, Cockwell P, Reid S, Chandler K, Mead GP, Harrison J, Hattersley J, Evans ND, Chappell MJ, Cook M, Goehl H, Storr M, Bradwell AR. Efficient removal of immunoglobulin free light chains by hemodialysis for multiple myeloma: in vitro and in vivo studies. J Am Soc Nephrol. 2007 Mar;18(3):886-95. doi: 10.1681/ASN.2006080821. Epub 2007 Jan 17.
- Related InfoLink provided by the sponsor.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing High Cut-off Hemodialysis and Chemotherapy in people with Primary Amyloidosis of Light Chain Type, run by Fondazione IRCCS Policlinico San Matteo di Pavia at 1 site 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 8 inclusion and 8 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: withdrawn, as of the sponsor's last update on 21 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 was withdrawn before enrolling participants, so there are no results.
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?
Survival (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01531751, which also lists 1 linked publication.
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 21 Mar 2018.