Clinical trial NCT02966522: Thalidomide/Dexamethasone Treatment And PET Evaluation In Organ Involvemenet of Cardiac Amyloidosis
Official title: Frontline Thalidomide for Amyloidosis Involving Myocardium: Investigation of Organ Reversing Capacity of Lenalidomide
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Cardiac Amyloidosis
Keywords: Thalidoide
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
Collaborators: name: CW pharmaceutical company
First posted: 2016-11-17
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Hematologic response
timeFrame: through study completion, an average of 1 year
Secondary outcomes:
measure: Cardiac response
timeFrame: through study completion, an average of 1 year
measure: Maximal LV myocardium-blood cavity ratio
timeFrame: through study completion, an average of 1 year
measure: Overall survival
timeFrame: From date of enrollment until the date of death from any cause, assessed up to 60 months
measure: Progression-free survival
timeFrame: 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
measure: Toxicity profile related to thalidomide, according to CTCAE version 4.03
timeFrame: through study completion, an average of 1 year
measure: Renal response
timeFrame: through study completion, an average of 1 year
measure: Hepatic response
timeFrame: through study completion, an average of 1 year
measure: Mean LV myocardium-blood cavity ratio
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Seoul National University Hospital
name: Youngil Koh, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Kastritis E, Terpos E, Roussou M, Gavriatopoulou M, Pamboukas C, Boletis I, Marinaki S, Apostolou T, Nikitas N, Gkortzolidis G, Michalis E, Delimpasi S, Dimopoulos MA. A phase 1/2 study of lenalidomide with low-dose oral cyclophosphamide and low-dose dexamethasone (RdC) in AL amyloidosis. Blood. 2012 Jun 7;119(23):5384-90. doi: 10.1182/blood-2011-12-396903. Epub 2012 Apr 18.
citation: Lee SP, Lee ES, Choi H, Im HJ, Koh Y, Lee MH, Kwon JH, Paeng JC, Kim HK, Cheon GJ, Kim YJ, Kim I, Yoon SS, Seo JW, Sohn DW. 11C-Pittsburgh B PET imaging in cardiac amyloidosis. JACC Cardiovasc Imaging. 2015 Jan;8(1):50-59. doi: 10.1016/j.jcmg.2014.09.018. Epub 2014 Nov 4.