Epigallocatechingallate (EGCG) in Cardiac AL Amyloidosis

Study Overview
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Brief Summary
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In a proportion of patients with AL amyloidosis there is no improvement of cardiac function despite hematologic response to treatment. The aim of the study is to assess whether treatment with EGCG increases the rate of cardiac response in patients with AL amyloidosis who completed chemotherapy.

Detailed Description
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This will be a phase II open-label randomized trial. Patients with AL amyloidosis and cardiac involvement who have achieved at least partial hematologic response after chemotherapy will be randomized to receive standard supportive therapy (SST) or SST plus Epigallocatechin gallate (EGCG). After giving written informed consent, the patients will be evaluated for eligibility. Briefly, the subjects with a biopsy-proven diagnosis of AL amyloidosis who achieved at least partial response after chemotherapy, who are not planned to receive further chemotherapy and who have significant cardiac dysfunction will be considered eligible. The patients will be stratified according to the quality of hematologic response and to the severity of cardiac involvement. Following stratification, the patients will be randomized to receive SST or SST plus EGCG. The study comprises 3 periods: screening (including stratification and randomization), treatment (with evaluations of response every 2 months) followed by the end-of-treatment evaluation and follow-up. Therapy will continue for up to 1 year. After treatment patients will be followed for 3 years.

Official Title
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A Phase II Open-label Randomized Study of Dietary Supplement With Epigallocatechin Gallate (EGCG) to Improve Cardiac Dysfunction in Patients With AL Amyloidosis Who do Not Require Chemotherapy (EpiCardiAL)

Conditions
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Primary Amyloidosis of Light Chain Type

Intervention / Treatment
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* Drug: Diuretics (plus antiarrhythmic drugs, i.e. amiodarone, in case of complex ventricular arrhithmias)
* Drug: Diuretics (plus antiarrhythmic drugs, i.e. amiodarone, in case of complex ventricular arrhythmias) plus EGCG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of AL amyloidosis. Age ≥18 years. The patients must have been treated for AL amyloidosis attaining hematologic response. Evidence of cardiac involvement at echocardiography (mean left ventricular wall thickness >12 mm in the absence of other causes). NT-proBNP ≥650 ng/L Exclusion Criteria: Non-AL (e.g. familial, senile) amyloidosis. Concomitant non-amyloid related clinically significant cardiac diseases. Need of further chemotherapy for AL amyloidosis. Estimated glomerular filtration rate (eGFR) <30 mL/min per 1.73 m2. Uncontrolled infection. Inability to give informed consent. Previous or ongoing psychiatric illness (excluding reactive depression). Pregnant or nursing women.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A<br>The patients will be divided into 4 strata according to cardiac dysfunction and to the quality of hematologic response. After stratification the patients will be randomized (1:1) within each stratum to receive Standard Therapy alone (Arm A) or Standard Therapy plus Investigational Drug (Arm B). | Drug: Diuretics (plus antiarrhythmic drugs, i.e. amiodarone, in case of complex ventricular arrhithmias)<br>* Antiarrhythmic drugs (i.e. amiodarone), angiotensins which transform inhibitor enzymes, and/or beta-blockers if tolerated.<br>|
| Experimental: Arm B<br>The patients will be divided into 4 strata according to cardiac dysfunction and to the quality of hematologic response. After stratification the patients will be randomized (1:1) within each stratum to receive Standard Therapy alone (Arm A) or Standard Therapy plus Investigational Drug (Arm B) | Drug: Diuretics (plus antiarrhythmic drugs, i.e. amiodarone, in case of complex ventricular arrhythmias) plus EGCG<br>* Antiarrhythmic drugs (i.e. amiodarone), angiotensins which transform inhibitor enzymes, and/or beta-blockers if tolerated. EGCG, 675 mg/day, oral, for one year.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac response | The primary objective is to assess whether treatment with EGCG increases the rate of cardiac response following chemotherapy in patients with AL amyloidosis. The primary endpoint is cardiac response at 6 months. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of adverse events | The secondary objectives are to assess the safety of EGCG in cardiac AL amyloidosis, to determine whether EGCG can prevent or delay cardiac progression and to compare survival of patients receiving EGCG compared to subjects receiving SST. | 6 months | 
| Rate of cardiac progression | The secondary objectives are to assess the safety of EGCG in cardiac AL amyloidosis, to determine whether EGCG can prevent or delay cardiac progression and to compare survival of patients receiving EGCG compared to subjects receiving SST. | 6 months | 
| Time to cardiac progression | The secondary objectives are to assess the safety of EGCG in cardiac AL amyloidosis, to determine whether EGCG can prevent or delay cardiac progression and to compare survival of patients receiving EGCG compared to subjects receiving SST. | 6 months | 
| Rate of cardiac events | The secondary objectives are to assess the safety of EGCG in cardiac AL amyloidosis, to determine whether EGCG can prevent or delay cardiac progression and to compare survival of patients receiving EGCG compared to subjects receiving SST. | 6 months | 
| Time to cardiac events | The secondary objectives are to assess the safety of EGCG in cardiac AL amyloidosis, to determine whether EGCG can prevent or delay cardiac progression and to compare survival of patients receiving EGCG compared to subjects receiving SST. | 6 months | 
| Survival | The secondary objectives are to assess the safety of EGCG in cardiac AL amyloidosis, to determine whether EGCG can prevent or delay cardiac progression and to compare survival of patients receiving EGCG compared to subjects receiving SST. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epigallocatechin gallate, AL amyloidosis