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

NCT ID: NCT01531751

Last Updated: 2018-03-21

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-28
• Study Completion Date: 2015-12-31

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.

Conditions

Primary Amyloidosis of Light Chain Type

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

High Cut-off Hemodialysis

Group Type: EXPERIMENTAL

High Cut-off Hemodialysis

Intervention Type: DEVICE

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.

Chemotherapy

Intervention Type: DRUG

Chemotherapy will be based on alchilators, proteasome inhibitors, steroids, IMiDs.

Interventions

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.

Intervention Type: DEVICE

Chemotherapy

Chemotherapy will be based on alchilators, proteasome inhibitors, steroids, IMiDs.

Intervention Type: DRUG

Other Intervention Names

Theralite

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Fondazione IRCCS Policlinico San Matteo di Pavia

OTHER

Sponsor Role: lead

Responsible Party

Giampaolo Merlini

Director, Amyloidosis Research and Treatment Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

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

Pavia, , Italy

Countries

Italy

References

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.

Reference Type: BACKGROUND

PMID: 17229909 (View on PubMed)

Related Links

http://www.amiloidosi.it/

Related Info

Other Identifiers

AC-005-IT

Identifier Type: -

Identifier Source: org_study_id