Cardiac Amyloidosis
Conditions
Keywords
Thalidoide
Brief summary
To prove the organ-reversing potential of thalidomide for amyloidosis with cardiac involvement
Detailed description
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.
Interventions
DRUGThalidomide
DRUGDexamethasone
Sponsors
CW pharmaceutical company
Seoul National University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age : more than 18 years old 2. 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 3. ECOG(Eastern Cooperative Oncology Group) performance status ≤ 3 4. 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 5. Expected survival \> 3 months 6. 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
1. Amyloidosis without cardiac involvement 2. Patients who are planning to receive autologous stem cell transplantation 3. Patients who received autologous stem cell transplantation, remained in hematologic complete response 4. Pregnant, lactating or unwilling to use adequate contraception 5. Systemic infection unless specific anti-infective therapy is employed 6. Known allergies to thalidomide 7. Previous experimental agents or approved anti-tumor treatment within 1 months before the date of registration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hematologic response | through study completion, an average of 1 year | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximal LV myocardium-blood cavity ratio | through study completion, an average of 1 year | estimated by 11C-Pittsburge B PET imaging |
| 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 | — |
| Cardiac response | through study completion, an average of 1 year | \> 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 |
| Renal response | through study completion, an average of 1 year | \> 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 |
| Hepatic response | through study completion, an average of 1 year | ≥ 50% decrease in alkaline phosphatase levels and/or ≥ 2cm decrease in liver size (assessed by radiograph) |
| Mean LV myocardium-blood cavity ratio | through study completion, an average of 1 year | estimated by 11C-Pittsburge B PET imaging |
| Toxicity profile related to thalidomide, according to CTCAE version 4.03 | through study completion, an average of 1 year | — |
Countries
South Korea
Contacts
Primary ContactRyul Kim, MD
Outcome results
None listed