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Amyloidosis

Constriction, Pathologic

Immunoglobulin Light-chain Amyloidosis

Spinal Stenosis

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AL Amyloidosis

Familial Transthyretin Amyloidosis

Biopsy of ligamentum flavum tissue during spinal stenosis surgery sent to pathology for amyloid-specific analysis

During clinically-scheduled spinal stenosis surgery, ligamentum flavum tissue (which may contain surrounding tissue and subcutaneous fat) that is removed during the procedure will be sent to pathology to be analyzed with amyloid-specific staining.

Biopsy

Mazen A Hanna, MD

The investigators will prospectively evaluate for the presence of amyloid deposits in ligamentum flavum (yellow ligament) tissue samples obtained from patients undergoing spinal stenosis surgery. Patients who have tissue that stains positive for amyloid will be referred to an amyloidosis specialist.

Similar to carpal tunnel syndrome, spinal stenosis is associated with systemic amyloidosis and presents earlier than cardiac amyloidosis symptoms - 21-45% of ATTR patients and case reports in AL patients. The investigators' recent study found that 10% of older patients undergoing carpal tunnel release surgery were positive for amyloidosis, with 20% of that group presenting with cardiac involvement. 70% of the amyloid-positive group had a history of spinal stenosis and 40% required surgical intervention. Surgical intervention for spinal stenosis could provide an opportunity to screen for amyloidosis through yellow ligament (ligamentum flavum) biopsy.

This study will look at the prevalence of amyloidosis in patients undergoing surgical intervention for non-congenital spinal stenosis and spondyloarthropathy. The investigators hypothesize that 10% of such patients will be positive for amyloidosis.

Ligamentum flavum tissue (may contain surrounding tissue and subcutaneous fat)

Screening for Systemic Amyloidosis Via the Ligamentum Flavum

Incidence of amyloid deposits in removed ligamentum flavum tissue of older patients undergoing spinal stenosis surgery

The Cleveland Clinic

Principle Investigator

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Kidney Diseases

Kidney Failure, Chronic

Renal Insufficiency

Urologic Diseases

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Female Urogenital Diseases

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Female Urogenital Diseases and Pregnancy Complications

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Renal Insufficiency, Chronic

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

All Drugs and Chemicals

Proteasome Inhibitors

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.

High Cut-off Hemodialysis

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

Chemotherapy

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.

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.

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

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

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.

IRCCS Policlinico S. Matteo

Director, Amyloidosis Research and Treatment Center

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Screening for Systemic Amyloidosis Via the Ligamentum Flavum	NCT03923920	Amyloid Amyloidosis Spinal Stenosis Transthyretin A... Primary Amyloid...	Biopsy	50 Years -	The Cleveland Clinic
High Cut-off Hemodialysis in Patients With Advanced Cardiac AL Amyloidosis and End Stage Renal Disease	NCT01531751	Primary Amyloid...	High Cut-off He... Chemotherapy	18 Years -	IRCCS Policlinico S. Matteo

Spots Global Cancer Trial Database for primary amyloidosis of light chain type