High Cut-off Hemodialysis in Patients With Advanced Cardiac AL Amyloidosis and End Stage Renal Disease (DIACAL)
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.
Primary Amyloidosis of Light Chain Type
Device: High Cut-off Hemodialysis
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|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.|
- Survival [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]The primary objective will be to assess survival of patients with advanced cardiac AL amyloidosis treated with HCO-HD combined with chemotherapy.
- tolerability of the experimental device [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]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.
|Study Start Date:||February 2015|
|Estimated Study Completion Date:||December 2017|
|Estimated Primary Completion Date:||December 2017 (Final data collection date for primary outcome measure)|
|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 Name: TheraliteDrug: Chemotherapy
Chemotherapy will be based on alchilators, proteasome inhibitors, steroids, IMiDs.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01531751
|Contact: Giampaolo Merlini, Prof.||+39(0)firstname.lastname@example.org|
|Contact: Giovanni Palladini, Dr.||+39(0)email@example.com|
|Centro per lo Studio e la Cura delle Amiloidosi Sistemiche - Fondazione IRCCS Policlinico S.Matteo||Recruiting|
|Pavia, Italy, 27100|
|Contact: Giovanni Palladini, Dr. +39(0)382502994 firstname.lastname@example.org|
|Contact: Leda Roggeri, Dr. +39(0)382502994 email@example.com|
|Principal Investigator: Giampaolo Merlini, Prof.|
|Sub-Investigator: Giovanni Palladini, Dr.|