<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/NCT01728259</url>
  </required_header>
  <id_info>
    <org_study_id>2011-155</org_study_id>
    <nct_id>NCT01728259</nct_id>
  </id_info>
  <brief_title>First-line Pomalidomide, Bortezomib, and Dexamethasone For AL Amyloidosis or LCDD</brief_title>
  <official_title>Phase I Study of Pomalidomide, Bortezomib, and Dexamethasone (PVD) as First-Line Treatment of AL Amyloidosis or Light Chain Deposition Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Barbara Ann Karmanos Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Barbara Ann Karmanos Cancer Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase I trial studies the side effects and best dose of pomalidomide and bortezomib when&#xD;
      given together with dexamethasone in treating patients with amyloid light-chain amyloidosis&#xD;
      or light chain deposition disease. Biological therapies, such as pomalidomide, may stimulate&#xD;
      the immune system in different ways and stop abnormal cells from growing. Bortezomib may stop&#xD;
      the growth of abnormal cells by blocking some of the enzymes needed for cell growth. Giving&#xD;
      pomalidomide and bortezomib together with dexamethasone may be an effective treatment for&#xD;
      amyloid light-chain amyloidosis or light chain deposition disease&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. Establish the maximum tolerated dose (MTD) of the combination of pomalidomide, bortezomib,&#xD;
      and dexamethasone (PVD) to take forward in a subsequent phase 2 study.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Obtain a preliminary assessment of efficacy of PVD regimen as initial treatment of amyloid&#xD;
      light-chain (AL) or light chain deposition disease (LCDD).&#xD;
&#xD;
      OUTLINE: This is a dose-escalation study of pomalidomide and bortezomib.&#xD;
&#xD;
      Patients receive pomalidomide orally (PO) on days 1-21; bortezomib intravenously (IV) on days&#xD;
      1, 8, and 15; and dexamethasone PO on days 1, 8, 15, and 22. Courses repeat every 28 days in&#xD;
      the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at least every 3 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    FDA placed the study on a clinical hold, due to the concerns by the FDA and Health Canada,&#xD;
    Celgene decided to permanently close the study.&#xD;
  </why_stopped>
  <start_date type="Actual">March 2013</start_date>
  <completion_date type="Actual">October 31, 2018</completion_date>
  <primary_completion_date type="Actual">October 31, 2018</primary_completion_date>
  <phase>Phase 1</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>Maximum tolerated dose defined as the dose level before 2 of 6 patients experience dose-limiting toxicity (DLT) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0</measure>
    <time_frame>28 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Complete hematologic response rate (hCR)</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Will be estimated and reported with 95% confidence intervals.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall hematologic response rate (partial response [PR] + complete response [CR])</measure>
    <time_frame>Up to 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Organ response rates (heart, liver, kidney)</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Organ responses will be tabulated and reported for all patients with cardiac, renal, hepatic, and/or neurologic involvement by amyloidosis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>From date of registration to date of death, assessed up to 28 days</time_frame>
    <description>Will be estimated and reported with 95% confidence interval.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Will be estimated and reported with 95% confidence interval.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Light Chain Deposition Disease</condition>
  <condition>Primary Systemic Amyloidosis</condition>
  <arm_group>
    <arm_group_label>Treatment (pomalidomide, bortezomib, and dexamethasone)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive pomalidomide PO on days 1-21; bortezomib IV or SC on days 1, 8, and 15; and dexamethasone PO on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>pomalidomide</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (pomalidomide, bortezomib, and dexamethasone)</arm_group_label>
    <other_name>CC-4047</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>bortezomib</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (pomalidomide, bortezomib, and dexamethasone)</arm_group_label>
    <other_name>LDP 341</other_name>
    <other_name>MLN341</other_name>
    <other_name>VELCADE</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>dexamethasone</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (pomalidomide, bortezomib, and dexamethasone)</arm_group_label>
    <other_name>Aeroseb-Dex</other_name>
    <other_name>Decaderm</other_name>
    <other_name>Decadron</other_name>
    <other_name>DM</other_name>
    <other_name>DXM</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (pomalidomide, bortezomib, and dexamethasone)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Understand and voluntarily sign an informed consent form&#xD;
&#xD;
          -  Able to adhere to protocol requirements&#xD;
&#xD;
          -  Histologically confirmed AL or LCDD (any time prior to screening)&#xD;
&#xD;
          -  Up to 1 cycle of prior therapy allowed (maximum of 120 mg total dexamethasone (or&#xD;
             equivalent amount of prednisone), 4 days of melphalan, and/or 4 doses of velcade; at&#xD;
             least 4 wks has to have had passed since last dose of melphalan, 2 wks since last&#xD;
             velcade or glucocorticoid dose&#xD;
&#xD;
          -  Measurable light chain elevation, as defined by:&#xD;
&#xD;
               -  A difference between the involved immunoglobulin free light chain and uninvolved&#xD;
                  light chain and uninvolved light chain (dFLC) of &gt;= 5 mg/dL AND abnormal serum&#xD;
                  immunoglobulin kappa lambda free light chain ratio&#xD;
&#xD;
               -  EXCEPTION: during the DOSE ESCALATION PORTION of the study only, a measurable&#xD;
                  M-protein (&gt;= 0.5 g/dL) on serum protein electrophoresis (SPEP) or a measurable&#xD;
                  urinary light chain (&gt;= 200 mg/24 hrs) by urine protein electrophoresis (UPEP)&#xD;
                  without a dFLC meeting the above criteria is acceptable; subjects without a dFLC&#xD;
                  &gt;= 5 mg/dL treated at the MTD will not count towards the expansion cohort&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of =&lt; 2 at study entry&#xD;
&#xD;
          -  Demonstrated clonal population of plasma cells in the bone marrow or positive&#xD;
             immunohistochemical stain with anti-light chain anti-sera of amyloid fibrils&#xD;
&#xD;
          -  NTproBNP &lt; 8500 pg/mL&#xD;
&#xD;
          -  Absolute neutrophil count &gt;= 1000/mm^3&#xD;
&#xD;
          -  Platelet count &gt;= 75,000/mm^3&#xD;
&#xD;
          -  Serum creatinine =&lt; 2.5 mg/dL&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 mg/dL&#xD;
&#xD;
          -  AST(SGOT) and ALT(SGPT) =&lt; 3 x upper limit of normal (ULN)&#xD;
&#xD;
          -  All study participants must be registered into the mandatory POMALYST REMS™ program,&#xD;
             and be willing and able to comply with the requirements of the POMALYST REMS™ program&#xD;
&#xD;
          -  Disease free of prior malignancies for &gt; or = 2 years with exception of treated basal&#xD;
             cell or squamous cell carcinoma of the skin. Carcinoma &quot;in situ&quot; of the cervix or&#xD;
             breast, or low-risk localized prostate cancer does not outright exclude patients, but&#xD;
             such cases need to be discussed with Dr. Zonder prior to enrollment.&#xD;
&#xD;
          -  Females of childbearing potential (FCBP) must have negative serum or urine pregnancy&#xD;
             test with a sensitivity of at least 25 mIU/mL within 10-14 days prior to and again&#xD;
             within 24 hours of starting pomalidomide and must either commit to continued&#xD;
             abstinence from heterosexual intercourse or begin TWO acceptable methods of birth&#xD;
             control, one highly effective method and one additional effective method AT THE SAME&#xD;
             TIME, at least 28 days before she starts taking pomalidomide; FCBP must also agree to&#xD;
             ongoing pregnancy testing; men must agree to use a latex condom during sexual contact&#xD;
             with a FCBP even if they have had a vasectomy; all patients must be counseled at a&#xD;
             minimum of every 28 days about pregnancy precautions and risks of fetal exposure&#xD;
&#xD;
          -  Able to take aspirin (ASA;81 or 325 mg) daily as prophylactic anticoagulation&#xD;
             (patients intolerant to ASA may use warfarin or low molecular weight heparin), unless&#xD;
             baseline prothrombin time [PT] or partial thromboplastin time [PTT] is &gt;= 1.5 ULN, in&#xD;
             which case thromboprophylaxis not required&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any serious medical condition, laboratory abnormality, or psychiatric illness that&#xD;
             would prevent the subject from signing the informed consent form&#xD;
&#xD;
          -  Pregnant or breast feeding females; (lactating females must agree not to breast feed&#xD;
             while taking pomalidomide)&#xD;
&#xD;
          -  Any condition, including the presence of laboratory abnormalities, which places the&#xD;
             subject at unacceptable risk if he/she were to participate in the study or confounds&#xD;
             the ability to interpret data from the study&#xD;
&#xD;
          -  Use of any other experimental drug or therapy within 28 days of baseline&#xD;
&#xD;
          -  Known hypersensitivity reaction or history of desquamating rash related to thalidomide&#xD;
             or lenalidomide&#xD;
&#xD;
          -  Known hypersensitivity to bortezomib, boron, or any of the other agents utilized in&#xD;
             this protocol&#xD;
&#xD;
          -  Patient has &gt;= grade 3 peripheral sensory neuropathy or &gt;= grade 2 painful sensory&#xD;
             neuropathy within 14 days before enrollment; (NOTE: patient with peripheral neuropathy&#xD;
             [PN] that was previously this severe but is currently improved due to ongoing therapy&#xD;
             [e.g., gabapentin or amitriptyline] may be eligible)&#xD;
&#xD;
          -  Myocardial infarction within 6 months prior to enrollment or has New York Heart&#xD;
             Association (NYHA) class III or IV heart failure, uncontrolled angina, severe&#xD;
             uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute&#xD;
             ischemia or active conduction system abnormalities (not including 1st degree&#xD;
             atrioventricular (AV)-block, Wenckebach type 2nd degree heart block, or left bundle&#xD;
             branch block; prior to study entry, any electrocardiogram (ECG) abnormality at&#xD;
             screening has to be documented by the investigator as not medically relevant); note:&#xD;
             there is no lower limit of left ventricular ejection fraction below which patients are&#xD;
             excluded from participation&#xD;
&#xD;
          -  Concurrent use of other anti-cancer agents or treatments&#xD;
&#xD;
          -  Known positive for human immunodeficiency virus (HIV) or infectious hepatitis, type A,&#xD;
             B or C&#xD;
&#xD;
          -  Meets criteria for symptomatic multiple myeloma, defined as:&#xD;
&#xD;
               -  &gt;= 10% monoclonal plasma cells in the marrow AND ANY OF THE FOLLOWING:&#xD;
&#xD;
                    -  Biopsy-confirmed plasmacytoma&#xD;
&#xD;
                    -  Lytic bone lesion(s)&#xD;
&#xD;
                    -  Hypercalcemia without other explanation&#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>Jeffrey Zonder</last_name>
    <role>Principal Investigator</role>
    <affiliation>Barbara Ann Karmanos Cancer Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Colorado Blood Cancer Institute</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boston University School of Medicine</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02118-2393</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Barbara Ann Karmanos Cancer Institute</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Princess Margaret Cancer Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>New Zealand</country>
  </removed_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>November 13, 2012</study_first_submitted>
  <study_first_submitted_qc>November 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 19, 2012</study_first_posted>
  <last_update_submitted>May 5, 2023</last_update_submitted>
  <last_update_submitted_qc>May 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Barbara Ann Karmanos Cancer Institute</investigator_affiliation>
    <investigator_full_name>Jeffrey Zonder</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Immunoglobulin Light-chain Amyloidosis</mesh_term>
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Amyloidosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexamethasone</mesh_term>
    <mesh_term>Bortezomib</mesh_term>
    <mesh_term>Pomalidomide</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/NCT01728259
org study id: 2011-155
nct id: NCT01728259
lead sponsor: 
has dmc: Yes
This phase I trial studies the side effects and best dose of pomalidomide and bortezomib when
      given together with dexamethasone in treating patients with amyloid light-chain amyloidosis
      or light chain deposition disease. Biological therapies, such as pomalidomide, may stimulate
      the immune system in different ways and stop abnormal cells from growing. Bortezomib may stop
      the growth of abnormal cells by blocking some of the enzymes needed for cell growth. Giving
      pomalidomide and bortezomib together with dexamethasone may be an effective treatment for
      amyloid light-chain amyloidosis or light chain deposition disease
PRIMARY OBJECTIVES:

      I. Establish the maximum tolerated dose (MTD) of the combination of pomalidomide, bortezomib,
      and dexamethasone (PVD) to take forward in a subsequent phase 2 study.

      SECONDARY OBJECTIVES:

      I. Obtain a preliminary assessment of efficacy of PVD regimen as initial treatment of amyloid
      light-chain (AL) or light chain deposition disease (LCDD).

      OUTLINE: This is a dose-escalation study of pomalidomide and bortezomib.

      Patients receive pomalidomide orally (PO) on days 1-21; bortezomib intravenously (IV) on days
      1, 8, and 15; and dexamethasone PO on days 1, 8, 15, and 22. Courses repeat every 28 days in
      the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at least every 3 months.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerated dose defined as the dose level before 2 of 6 patients experience dose-limiting toxicity (DLT) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
time frame: 28 days
measure: Complete hematologic response rate (hCR)
time frame: Up to 28 days
description: Will be estimated and reported with 95% confidence intervals.
measure: Overall hematologic response rate (partial response [PR] + complete response [CR])
time frame: Up to 28 days
measure: Organ response rates (heart, liver, kidney)
time frame: Up to 28 days
description: Organ responses will be tabulated and reported for all patients with cardiac, renal, hepatic, and/or neurologic involvement by amyloidosis.
measure: Overall survival
time frame: From date of registration to date of death, assessed up to 28 days
description: Will be estimated and reported with 95% confidence interval.
measure: Progression free survival
time frame: Up to 28 days
description: Will be estimated and reported with 95% confidence interval.
arm group label: Treatment (pomalidomide, bortezomib, and dexamethasone)
arm group type: Experimental
description: Patients receive pomalidomide PO on days 1-21; bortezomib IV or SC on days 1, 8, and 15; and dexamethasone PO on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: pomalidomide
description: Given PO
arm group label: Treatment (pomalidomide, bortezomib, and dexamethasone)
other name: CC-4047
intervention type: Drug
intervention name: bortezomib
description: Given IV
arm group label: Treatment (pomalidomide, bortezomib, and dexamethasone)
other name: LDP 341
other name: MLN341
other name: VELCADE
intervention type: Drug
intervention name: dexamethasone
description: Given PO
arm group label: Treatment (pomalidomide, bortezomib, and dexamethasone)
other name: Aeroseb-Dex
other name: Decaderm
other name: Decadron
other name: DM
other name: DXM
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment (pomalidomide, bortezomib, and dexamethasone)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jeffrey Zonder
role: Principal Investigator
affiliation: Barbara Ann Karmanos Cancer Institute
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
country: United States
country: New Zealand
responsible party type: Principal Investigator
investigator affiliation: Barbara Ann Karmanos Cancer Institute
investigator full name: Jeffrey Zonder
investigator title: Principal Investigator
mesh term: Immunoglobulin Light-chain Amyloidosis
mesh term: Multiple Myeloma
mesh term: Amyloidosis
mesh term: Dexamethasone
mesh term: Bortezomib
mesh term: Pomalidomide