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High Cut-off Hemodialysis in Patients With Advanced Cardiac AL Amyloidosis and End Stage Renal Disease (DIACAL)

Primary Purpose

Primary Amyloidosis of Light Chain Type

Status
Withdrawn
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
High Cut-off Hemodialysis
Chemotherapy
Sponsored by
IRCCS Policlinico S. Matteo
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Amyloidosis of Light Chain Type focused on measuring HCO-HD, survival, cardiac biomarkers, AL amyloidosis, Light Chain Amyloidosis

Eligibility Criteria

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

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Sites / Locations

  • Centro per lo Studio e la Cura delle Amiloidosi Sistemiche - Fondazione IRCCS Policlinico S.Matteo

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

High Cut-off Hemodialysis

Arm Description

Outcomes

Primary Outcome Measures

Survival
The primary objective will be to assess survival of patients with advanced cardiac AL amyloidosis treated with HCO-HD combined with chemotherapy.

Secondary Outcome Measures

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.

Full Information

First Posted
January 11, 2012
Last Updated
March 20, 2018
Sponsor
IRCCS Policlinico S. Matteo
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1. Study Identification

Unique Protocol Identification Number
NCT01531751
Brief Title
High Cut-off Hemodialysis in Patients With Advanced Cardiac AL Amyloidosis and End Stage Renal Disease
Acronym
DIACAL
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.
Study Type
Interventional

2. Study Status

Record Verification Date
March 2018
Overall Recruitment Status
Withdrawn
Study Start Date
February 2015 (Actual)
Primary Completion Date
December 2015 (Actual)
Study Completion Date
December 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
IRCCS Policlinico S. Matteo

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Amyloidosis of Light Chain Type
Keywords
HCO-HD, survival, cardiac biomarkers, AL amyloidosis, Light Chain Amyloidosis

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
High Cut-off Hemodialysis
Arm Type
Experimental
Intervention Type
Device
Intervention Name(s)
High Cut-off Hemodialysis
Other Intervention Name(s)
Theralite
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Chemotherapy
Intervention Description
Chemotherapy will be based on alchilators, proteasome inhibitors, steroids, IMiDs.
Primary Outcome Measure Information:
Title
Survival
Description
The primary objective will be to assess survival of patients with advanced cardiac AL amyloidosis treated with HCO-HD combined with chemotherapy.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
tolerability of the experimental device
Description
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.
Time Frame
1 month

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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.
Facility Information:
Facility Name
Centro per lo Studio e la Cura delle Amiloidosi Sistemiche - Fondazione IRCCS Policlinico S.Matteo
City
Pavia
ZIP/Postal Code
27100
Country
Italy

12. IPD Sharing Statement

Citations:
PubMed Identifier
17229909
Citation
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.
Results Reference
background
Links:
URL
http://www.amiloidosi.it/
Description
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High Cut-off Hemodialysis in Patients With Advanced Cardiac AL Amyloidosis and End Stage Renal Disease

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