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

March 20, 2018 updated by: Giampaolo Merlini, IRCCS Policlinico S. Matteo

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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 Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Pavia, Italy, 27100
        • Centro per lo Studio e la Cura delle Amiloidosi Sistemiche - Fondazione IRCCS Policlinico S.Matteo

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: High Cut-off Hemodialysis
Device: High Cut-off Hemodialysis
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.
Other Names:
  • Theralite
Drug: Chemotherapy
Chemotherapy will be based on alchilators, proteasome inhibitors, steroids, IMiDs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
tolerability of the experimental device
Time Frame: 1 month
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.
1 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS Policlinico S. Matteo

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

February 1, 2015

Primary Completion (ACTUAL)

December 1, 2015

Study Completion (ACTUAL)

December 1, 2015

Study Registration Dates

First Submitted

January 11, 2012

First Submitted That Met QC Criteria

February 8, 2012

First Posted (ESTIMATE)

February 13, 2012

Study Record Updates

Last Update Posted (ACTUAL)

March 21, 2018

Last Update Submitted That Met QC Criteria

March 20, 2018

Last Verified

March 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AC-005-IT

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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