Thalidomide/Dexamethasone Treatment And PET Evaluation In Organ Involvemenet of Cardiac Amyloidosis

Study Overview
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Brief Summary
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To prove the organ-reversing potential of thalidomide for amyloidosis with cardiac involvement

Detailed Description
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Considering that dismal prognosis of amyloidosis is attributable to organ dysfunction, primary aim of amyloidosis treatment should be an organ reversal. However, due to various reasons, not much is known about organ reversal in amyloidosis. Almost all of the clinical trials evaluated hematologic response in amyloidosis. Meanwhile, besides autologous stem cell transplantation with high-dose melphalan conditioning, hematologic response rate of various agents such as bortezomib, melphalan, thalidomide and lenalidomide are similar for amyloidosis. However, organ reversing potential of these agents is not known. If there is a difference in organ reversing potential despite of similar hematologic response rate, drug with effective organ reversing potential should be a standard treatment for amyloidosis. The investigators assume that thalidomide could make organ reversal in cardiac amyloidosis due to its specific mechanism of action. To prove this concept, the investigators propose a clinical trial that evaluates organ reversing potential of thalidomide in cardiac amyloidosis.

Official Title
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Frontline Thalidomide for Amyloidosis Involving Myocardium: Investigation of Organ Reversing Capacity of Lenalidomide

Conditions
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Cardiac Amyloidosis

Intervention / Treatment
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* Drug: Thalidomide
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age : more than 18 years old Cardiac amyloidosis (both AL or AH type) patient who meet both (A and B) of the following criteria A. Cardiac involvement: meet one of the following criteria Echocardiography: mean wall thickness >12 mm, and no other cardiac cause NTproBNP >332 ng/l in the absence of renal failure Evidence of cardiac amyloidosis in cardiac MRI B. Treatment history: No history of exposure to thalidomide ECOG(Eastern Cooperative Oncology Group) performance status ≤ 3 Tolerable major organ function determined by laboratory examination i. Serum creatinine ≤ 3.0 mg/dl ii. Absolute neutrophil count ≥ 1000/μl iii. Platelet ≥ 75000/ μl iv. Hemoglobin ≥ 8.0 mg/dl v. Bilirubin < 2 times or Alkaline phosphate < 4 times upper limit of normal Expected survival > 3 months Female participants of child-bearing potential must have a negative pregnancy test prior to treatment and agree to use dual methods of contraception for the duration of the study and for 30 days following completion of study. Male participants must also agree to use a barrier method of contraception for the duration of the study and for 30 days following completion of study if sexually active with a female of child-bearing potential. Exclusion Criteria: Amyloidosis without cardiac involvement Patients who are planning to receive autologous stem cell transplantation Patients who received autologous stem cell transplantation, remained in hematologic complete response Pregnant, lactating or unwilling to use adequate contraception Systemic infection unless specific anti-infective therapy is employed Known allergies to thalidomide Previous experimental agents or approved anti-tumor treatment within 1 months before the date of registration

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Thalidomide<br>Patient with cardiac amyloidosis receive thalilomide with dexamethasone | Drug: Thalidomide<br> <br> Drug: Dexamethasone<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hematologic response | Complete response: Normalization of FLC levels and κ to λ ratio, with nega-tive serum and urine immunofixation Very good partial response: de-creased of dFLC to < 40mg/l Partial response: > 50% reduction of dFLC | through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac response | > 30% and > 300 ng/l decrease in NTproBNP levels in patients with NTproBNP levels ≥ 650 ng/l at base-line or ≥ 2-class decrease in NYHA class in patients with NYHA class 3 or 4 at baseline | through study completion, an average of 1 year | 
| Maximal LV myocardium-blood cavity ratio | estimated by 11C-Pittsburge B PET imaging | through study completion, an average of 1 year | 
| Overall survival |  | From date of enrollment until the date of death from any cause, assessed up to 60 months | 
| Progression-free survival |  | From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months | 
| Toxicity profile related to thalidomide, according to CTCAE version 4.03 |  | through study completion, an average of 1 year | 
| Renal response | > 50% (≥ 5.0 g/d) decrease in 24h urine protein levels in patients with urine protein levels > 0.5 g/l at baseline without ≥ 25% increase in serum creatinine levels or decrease in creatinine clearance from baseline | through study completion, an average of 1 year | 
| Hepatic response | ≥ 50% decrease in alkaline phosphatase levels and/or ≥ 2cm decrease in liver size (assessed by radiograph) | through study completion, an average of 1 year | 
| Mean LV myocardium-blood cavity ratio | estimated by 11C-Pittsburge B PET imaging | through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thalidoide