<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02966522</url>
  </required_header>
  <id_info>
    <org_study_id>H-1512-129-730</org_study_id>
    <nct_id>NCT02966522</nct_id>
  </id_info>
  <brief_title>Thalidomide/Dexamethasone Treatment And PET Evaluation In Organ Involvemenet of Cardiac Amyloidosis</brief_title>
  <acronym>TaPiOCA</acronym>
  <official_title>Frontline Thalidomide for Amyloidosis Involving Myocardium: Investigation of Organ Reversing Capacity of Lenalidomide</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Seoul National University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>CW pharmaceutical company</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Seoul National University Hospital</source>
  <brief_summary>
    <textblock>
      To prove the organ-reversing potential of thalidomide for amyloidosis with cardiac&#xD;
      involvement&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Considering that dismal prognosis of amyloidosis is attributable to organ dysfunction,&#xD;
      primary aim of amyloidosis treatment should be an organ reversal. However, due to various&#xD;
      reasons, not much is known about organ reversal in amyloidosis. Almost all of the clinical&#xD;
      trials evaluated hematologic response in amyloidosis. Meanwhile, besides autologous stem cell&#xD;
      transplantation with high-dose melphalan conditioning, hematologic response rate of various&#xD;
      agents such as bortezomib, melphalan, thalidomide and lenalidomide are similar for&#xD;
      amyloidosis. However, organ reversing potential of these agents is not known. If there is a&#xD;
      difference in organ reversing potential despite of similar hematologic response rate, drug&#xD;
      with effective organ reversing potential should be a standard treatment for amyloidosis.&#xD;
&#xD;
      The investigators assume that thalidomide could make organ reversal in cardiac amyloidosis&#xD;
      due to its specific mechanism of action. To prove this concept, the investigators propose a&#xD;
      clinical trial that evaluates organ reversing potential of thalidomide in cardiac&#xD;
      amyloidosis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>October 2016</start_date>
  <completion_date type="Anticipated">September 2019</completion_date>
  <primary_completion_date type="Anticipated">September 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Hematologic response</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>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 &lt; 40mg/l Partial response: &gt; 50% reduction of dFLC</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cardiac response</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>&gt; 30% and &gt; 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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximal LV myocardium-blood cavity ratio</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>estimated by 11C-Pittsburge B PET imaging</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>From date of enrollment until the date of death from any cause, assessed up to 60 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>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</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Toxicity profile related to thalidomide, according to CTCAE version 4.03</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renal response</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>&gt; 50% (≥ 5.0 g/d) decrease in 24h urine protein levels in patients with urine protein levels &gt; 0.5 g/l at baseline without ≥ 25% increase in serum creatinine levels or decrease in creatinine clearance from baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hepatic response</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>≥ 50% decrease in alkaline phosphatase levels and/or ≥ 2cm decrease in liver size (assessed by radiograph)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean LV myocardium-blood cavity ratio</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>estimated by 11C-Pittsburge B PET imaging</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Cardiac Amyloidosis</condition>
  <arm_group>
    <arm_group_label>Thalidomide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patient with cardiac amyloidosis receive thalilomide with dexamethasone</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Thalidomide</intervention_name>
    <arm_group_label>Thalidomide</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <arm_group_label>Thalidomide</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age : more than 18 years old&#xD;
&#xD;
          2. Cardiac amyloidosis (both AL or AH type) patient who meet both (A and B) of the&#xD;
             following criteria A. Cardiac involvement: meet one of the following criteria&#xD;
&#xD;
               -  Echocardiography: mean wall thickness &gt;12 mm, and no other cardiac cause&#xD;
&#xD;
               -  NTproBNP &gt;332 ng/l in the absence of renal failure&#xD;
&#xD;
               -  Evidence of cardiac amyloidosis in cardiac MRI B. Treatment history: No history&#xD;
                  of exposure to thalidomide&#xD;
&#xD;
          3. ECOG(Eastern Cooperative Oncology Group) performance status ≤ 3&#xD;
&#xD;
          4. Tolerable major organ function determined by laboratory examination i. Serum&#xD;
             creatinine ≤ 3.0 mg/dl ii. Absolute neutrophil count ≥ 1000/μl iii. Platelet ≥ 75000/&#xD;
             μl iv. Hemoglobin ≥ 8.0 mg/dl v. Bilirubin &lt; 2 times or Alkaline phosphate &lt; 4 times&#xD;
             upper limit of normal&#xD;
&#xD;
          5. Expected survival &gt; 3 months&#xD;
&#xD;
          6. Female participants of child-bearing potential must have a negative pregnancy test&#xD;
             prior to treatment and agree to use dual methods of contraception for the duration of&#xD;
             the study and for 30 days following completion of study. Male participants must also&#xD;
             agree to use a barrier method of contraception for the duration of the study and for&#xD;
             30 days following completion of study if sexually active with a female of&#xD;
             child-bearing potential.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Amyloidosis without cardiac involvement&#xD;
&#xD;
          2. Patients who are planning to receive autologous stem cell transplantation&#xD;
&#xD;
          3. Patients who received autologous stem cell transplantation, remained in hematologic&#xD;
             complete response&#xD;
&#xD;
          4. Pregnant, lactating or unwilling to use adequate contraception&#xD;
&#xD;
          5. Systemic infection unless specific anti-infective therapy is employed&#xD;
&#xD;
          6. Known allergies to thalidomide&#xD;
&#xD;
          7. Previous experimental agents or approved anti-tumor treatment within 1 months before&#xD;
             the date of registration&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Youngil Koh, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Seoul National University Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ryul Kim, MD</last_name>
    <email>chrono0707@icloud.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Seoul National University Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>03080</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Youngil Koh, MD, PhD</last_name>
      <email>go01@snu.ac.kr</email>
    </contact>
    <contact_backup>
      <last_name>Ryul Kim, MD</last_name>
      <email>chrono0707@icloud.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <reference>
    <citation>Kastritis E, Dimopoulos MA. Recent advances in the management of AL Amyloidosis. Br J Haematol. 2016 Jan;172(2):170-86. doi: 10.1111/bjh.13805. Epub 2015 Oct 22.</citation>
    <PMID>26491974</PMID>
  </reference>
  <reference>
    <citation>Gatt ME, Palladini G. Light chain amyloidosis 2012: a new era. Br J Haematol. 2013 Mar;160(5):582-98. doi: 10.1111/bjh.12191. Epub 2013 Jan 7.</citation>
    <PMID>23294331</PMID>
  </reference>
  <reference>
    <citation>Dispenzieri A, Buadi F, Laumann K, LaPlant B, Hayman SR, Kumar SK, Dingli D, Zeldenrust SR, Mikhael JR, Hall R, Rajkumar SV, Reeder C, Fonseca R, Bergsagel PL, Stewart AK, Roy V, Witzig TE, Lust JA, Russell SJ, Gertz MA, Lacy MQ. Activity of pomalidomide in patients with immunoglobulin light-chain amyloidosis. Blood. 2012 Jun 7;119(23):5397-404. doi: 10.1182/blood-2012-02-413161. Epub 2012 Apr 4.</citation>
    <PMID>22493299</PMID>
  </reference>
  <reference>
    <citation>Dispenzieri A, Lacy MQ, Zeldenrust SR, Hayman SR, Kumar SK, Geyer SM, Lust JA, Allred JB, Witzig TE, Rajkumar SV, Greipp PR, Russell SJ, Kabat B, Gertz MA. The activity of lenalidomide with or without dexamethasone in patients with primary systemic amyloidosis. Blood. 2007 Jan 15;109(2):465-70. doi: 10.1182/blood-2006-07-032987. Epub 2006 Sep 28.</citation>
    <PMID>17008538</PMID>
  </reference>
  <reference>
    <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>
    <PMID>22517904</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>25499132</PMID>
  </reference>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>November 8, 2016</study_first_submitted>
  <study_first_submitted_qc>November 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 17, 2016</study_first_posted>
  <last_update_submitted>October 24, 2017</last_update_submitted>
  <last_update_submitted_qc>October 24, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 26, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Seoul National University Hospital</investigator_affiliation>
    <investigator_full_name>Youngil Koh</investigator_full_name>
    <investigator_title>Clinical professor</investigator_title>
  </responsible_party>
  <keyword>Thalidoide</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Amyloidosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thalidomide</mesh_term>
    <mesh_term>Dexamethasone</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02966522
org study id: H-1512-129-730
nct id: NCT02966522
lead sponsor: 
collaborator: 
To prove the organ-reversing potential of thalidomide for amyloidosis with cardiac
      involvement
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Hematologic response
time frame: through study completion, an average of 1 year
description: 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
measure: Cardiac response
time frame: through study completion, an average of 1 year
description: > 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
measure: Maximal LV myocardium-blood cavity ratio
time frame: through study completion, an average of 1 year
description: estimated by 11C-Pittsburge B PET imaging
measure: Overall survival
time frame: From date of enrollment until the date of death from any cause, assessed up to 60 months
measure: Progression-free survival
time frame: 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
time frame: through study completion, an average of 1 year
measure: Renal response
time frame: through study completion, an average of 1 year
description: > 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
measure: Hepatic response
time frame: through study completion, an average of 1 year
description: ≥ 50% decrease in alkaline phosphatase levels and/or ≥ 2cm decrease in liver size (assessed by radiograph)
measure: Mean LV myocardium-blood cavity ratio
time frame: through study completion, an average of 1 year
description: estimated by 11C-Pittsburge B PET imaging
arm group label: Thalidomide
arm group type: Experimental
description: Patient with cardiac amyloidosis receive thalilomide with dexamethasone
intervention type: Drug
intervention name: Thalidomide
arm group label: Thalidomide
intervention type: Drug
intervention name: Dexamethasone
arm group label: Thalidomide
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Youngil Koh, MD, PhD
role: Principal Investigator
affiliation: Seoul National University Hospital
last name: Ryul Kim, MD
email: chrono0707@icloud.com
facility: 
status: Recruiting
contact: 
contact backup: 
country: Korea, Republic of
citation: Kastritis E, Dimopoulos MA. Recent advances in the management of AL Amyloidosis. Br J Haematol. 2016 Jan;172(2):170-86. doi: 10.1111/bjh.13805. Epub 2015 Oct 22.
PMID: 26491974
citation: Gatt ME, Palladini G. Light chain amyloidosis 2012: a new era. Br J Haematol. 2013 Mar;160(5):582-98. doi: 10.1111/bjh.12191. Epub 2013 Jan 7.
PMID: 23294331
citation: Dispenzieri A, Buadi F, Laumann K, LaPlant B, Hayman SR, Kumar SK, Dingli D, Zeldenrust SR, Mikhael JR, Hall R, Rajkumar SV, Reeder C, Fonseca R, Bergsagel PL, Stewart AK, Roy V, Witzig TE, Lust JA, Russell SJ, Gertz MA, Lacy MQ. Activity of pomalidomide in patients with immunoglobulin light-chain amyloidosis. Blood. 2012 Jun 7;119(23):5397-404. doi: 10.1182/blood-2012-02-413161. Epub 2012 Apr 4.
PMID: 22493299
citation: Dispenzieri A, Lacy MQ, Zeldenrust SR, Hayman SR, Kumar SK, Geyer SM, Lust JA, Allred JB, Witzig TE, Rajkumar SV, Greipp PR, Russell SJ, Kabat B, Gertz MA. The activity of lenalidomide with or without dexamethasone in patients with primary systemic amyloidosis. Blood. 2007 Jan 15;109(2):465-70. doi: 10.1182/blood-2006-07-032987. Epub 2006 Sep 28.
PMID: 17008538
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.
PMID: 22517904
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.
PMID: 25499132
responsible party type: Principal Investigator
investigator affiliation: Seoul National University Hospital
investigator full name: Youngil Koh
investigator title: Clinical professor
mesh term: Amyloidosis
mesh term: Thalidomide
mesh term: Dexamethasone