<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/NCT01728207</url>
  </required_header>
  <id_info>
    <org_study_id>IMMU-114-01</org_study_id>
    <nct_id>NCT01728207</nct_id>
  </id_info>
  <brief_title>Phase I Dose Escalation Study of IMMU-114 in Relapsed or Refractory NHL and CLL</brief_title>
  <official_title>A Phase I Dose Escalation Study of Immunotherapy With IMMU-114 in Patients With Non-Hodgkin's Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gilead Sciences</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Gilead Sciences</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      IMMU-114 will be studied at different dose schedules and dose levels in order to assess the&#xD;
      highest dose safely tolerated. IMMU-114 will be administered subcutaneously (under the skin).&#xD;
      IMMU-114 will be given 1-2 times weekly for 3 weeks followed by one week of rest. This is&#xD;
      considered one cycle. Treatment cycles will be repeated until toxicity or worsening of&#xD;
      disease.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Study was stopped due to insufficient efficacy and very slow accrual&#xD;
  </why_stopped>
  <start_date>March 2013</start_date>
  <completion_date type="Actual">March 2017</completion_date>
  <primary_completion_date type="Actual">March 2017</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>Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)</measure>
    <time_frame>Safety will be assessed by measuring the change from baseline during treatment and up to 30 days after treatment</time_frame>
    <description>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical Response: o Measured by International Working Group Criteria for NHL patients. o Measured by IWCLL 2008 Guidelines for CLL patients.</measure>
    <time_frame>Efficacy will be assessed every 12 weeks during treatment and 4 weeks after the end of treatment</time_frame>
    <description>Responders will be defined as those with complete response (CR) or partial response (PR). Overall response rate (ORR) will be calculated as the number of evaluable responders divided by the total number of evaluable patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>During treatment and the changes at 4, 8 and 12 weeks after treatment and then every 3 months for up to 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>During treatment and the changes at 4, 8 and 12 weeks after treatment and then every 3 months for up to 2 years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Non-hodgkin's Lymphoma</condition>
  <condition>Follicular Lymphoma</condition>
  <condition>Mantle Cell Lymphoma</condition>
  <condition>Marginal Zone Lymphoma</condition>
  <condition>Chronic Lymphocytic Leukemia</condition>
  <condition>Small Lymphocytic Lymphoma</condition>
  <arm_group>
    <arm_group_label>IMMU-114</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>IMMU-114 will be administered subcutaneously (under the skin) once or twice weekly for 3 weeks followed by one week of rest. Treatment cycles will continue until disease worsening or toxicity. Various dose levels will be studied.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IMMU-114</intervention_name>
    <description>hL243 is a humanized antibody that targets HLA-DR, which is found on various b-cell hematologic malignancies and in autoimmune diseases.</description>
    <arm_group_label>IMMU-114</arm_group_label>
    <other_name>hL243</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Each patient with CLL/SLL must meet all of the following inclusion criteria to be&#xD;
             enrolled on the study:&#xD;
&#xD;
          -  Patients must have met the diagnostic criteria for CLL/SLL according to the IWCLL 2008&#xD;
             [13] or WHO Guidelines at some point during their disease course:&#xD;
&#xD;
          -  Patients with SLL: tumor biopsy immunohistochemistry diagnostic of SLL or blood/bone&#xD;
             marrow immunophenotype similar to CLL without lymphocytosis and enlarged lymph nodes.&#xD;
&#xD;
          -  Patient must have relapsed or refractory CLL/SLL following at least one purine&#xD;
             analog-containing regimen (or after one non-purine analog containing regimen if there&#xD;
             is a relative contraindication to purine-analog containing therapy) and not have&#xD;
             traditional options available or decline these. Patients with prolymphocytic leukemia&#xD;
             (PLL)-CLL or PLL transformation of CLL are eligible.&#xD;
&#xD;
          -  Patients must meet IWCLL 2008 Guideline [13] criteria for active disease requiring&#xD;
             treatment.&#xD;
&#xD;
        Each patient with NHL must meet all of the following inclusion criteria to be enrolled on&#xD;
        the study:&#xD;
&#xD;
          -  Patients with histologically confirmed B-cell NHL including marginal zone lymphoma,&#xD;
             follicular lymphoma, or mantle cell lymphoma by WHO criteria.&#xD;
&#xD;
          -  Patients must have relapsed or refractory disease after at least one prior therapy and&#xD;
             not have traditional options available or decline these.&#xD;
&#xD;
        All patients must meet all of the following inclusion criteria to be enrolled on the study:&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Able to understand and sign a written informed consent document.&#xD;
&#xD;
          -  Able to receive outpatient treatment and follow-up at the treating institution.&#xD;
&#xD;
          -  ECOG performance status 0-1.&#xD;
&#xD;
          -  Relapsed/refractory to at least one prior standard systemic treatment regimen, but no&#xD;
             more than 4.&#xD;
&#xD;
          -  Completed all prior therapies (immunosuppressive medications, antineoplastic therapy,&#xD;
             vaccination, immunotherapy, chemotherapy, radiotherapy, major surgery, etc) &gt;4 weeks&#xD;
             prior to the first study dose of medication (alemtuzumab ≥ 6 months).&#xD;
&#xD;
          -  If receiving corticosteroids, ≤ 20 mg/day prednisone or equivalent and unchanged&#xD;
&#xD;
          -  Patients capable of reproduction and male patients who have partners capable of&#xD;
             reproduction must agree to use an effective contraceptive method during the course of&#xD;
             the study and for 2 months following the completion of their last treatment.&#xD;
&#xD;
          -  Females of childbearing potential must have a negative serum β-Hcg pregnancy test&#xD;
             result within 7 days of first study dose. Female patients who are surgically&#xD;
             sterilized or who are &gt; 45 years old and have not experienced menses for &gt; 2 years may&#xD;
             have β- Hcg pregnancy test waived.&#xD;
&#xD;
          -  Required baseline laboratory data&#xD;
&#xD;
          -  Platelet count ≥ 75,000/mm3&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) ≥ 1500/mm3&#xD;
&#xD;
          -  AST/ALT ≤ 2.5 times upper limit of normal (ULN)&#xD;
&#xD;
          -  Creatinine and total bilirubin ≤ 1.5 times ULN&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients having received anti-CD20 therapy ≤ 4 weeks prior to the first study dose.&#xD;
&#xD;
          -  Patients having received alemtuzumab (anti-CD52) therapy ≤ 6 months prior to the first&#xD;
             study dose.&#xD;
&#xD;
          -  Patients having undergone prior allogeneic stem cell transplantation within 6 months&#xD;
             or having active graft versus host disease.&#xD;
&#xD;
          -  Patients with active Richter's syndrome (&gt;10% large B-cells in marrow).&#xD;
&#xD;
          -  Patients that have been designated Class III or IV by the New York Heart Association&#xD;
             Functional Classification.&#xD;
&#xD;
          -  Patients with a history of myocardial infarction or stroke within the last 6 months&#xD;
&#xD;
          -  Patients with transfusion-dependent anemia.&#xD;
&#xD;
          -  Patients with known hypersensitivity to any excipient contained in the drug&#xD;
             formulation.&#xD;
&#xD;
          -  Patients with a history of documented human anti-globulin antibodies.&#xD;
&#xD;
          -  Patients with active viral, bacterial or systemic fungal infection requiring&#xD;
             treatment.&#xD;
&#xD;
          -  Patients who are known to be HIV or hepatitis C positive.&#xD;
&#xD;
          -  Patients with a history of prior secondary malignancy that requires active systemic&#xD;
             therapy that will interfere with interpretation of efficacy or toxicity of IMMU-114,&#xD;
             or limit survival to 2 years. These patients should be discussed with the sponsor&#xD;
             prior to enrollment. Patients with basal or squamous skin carcinoma, cervical&#xD;
             carcinoma in situ on biopsy, localized breast cancer requiring hormonal therapy or&#xD;
             localized prostate cancer (Gleason score &lt; 5) do not require discussion.&#xD;
&#xD;
          -  Patients with active known CNS lymphoma. Patients with history of CNS leukemia now in&#xD;
             remission are eligible for the trial.&#xD;
&#xD;
          -  Patients who are pregnant or breast-feeding.&#xD;
&#xD;
          -  Patients with major surgery or radiation therapy within 4 weeks prior to first study&#xD;
             dose.&#xD;
&#xD;
          -  Patients must have recovered all toxicities from prior therapy or radiation to grade 1&#xD;
             or less (excluding alopecia).&#xD;
&#xD;
          -  Patients with substance abuse or other medical or psychiatric conditions that, in the&#xD;
             opinion of the investigator, would confound study interpretation or affect the&#xD;
             patient's ability to tolerate or complete the study.&#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>William Wegener, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Gilead Sciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Helen F Graham Cancer Center</name>
      <address>
        <city>Newark</city>
        <state>Delaware</state>
        <zip>19713</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nancy N. and J.C. Lewis Cancer and Research Pavilion</name>
      <address>
        <city>Savannah</city>
        <state>Georgia</state>
        <zip>31405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University Health Goshen Hospital</name>
      <address>
        <city>Goshen</city>
        <state>Indiana</state>
        <zip>46526</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ohio State University Comprehensive Cancer Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Huntsman Cancer Institute, Univ. Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Park KH, Sawada T, Murakami T, Ishii Y, Yasuo M, Fuchinoue S, Goldenberg DM, Kubota K. Anti-class II -DR humanized monoclonal antibody, IMMU-114, blocks allogeneic immune response. Am J Surg. 2012 Oct;204(4):527-34. doi: 10.1016/j.amjsurg.2011.11.017. Epub 2012 Jun 1.</citation>
    <PMID>22658578</PMID>
  </reference>
  <reference>
    <citation>Chen X, Chang CH, Stein R, Goldenberg DM. The humanized anti-HLA-DR moAb, IMMU-114, depletes APCs and reduces alloreactive T cells: implications for preventing GVHD. Bone Marrow Transplant. 2012 Jul;47(7):967-80. doi: 10.1038/bmt.2011.203. Epub 2011 Oct 24.</citation>
    <PMID>22020022</PMID>
  </reference>
  <reference>
    <citation>Rossi EA, Rossi DL, Cardillo TM, Stein R, Goldenberg DM, Chang CH. Preclinical studies on targeted delivery of multiple IFNalpha2b to HLA-DR in diverse hematologic cancers. Blood. 2011 Aug 18;118(7):1877-84. doi: 10.1182/blood-2011-03-343145. Epub 2011 Jun 16.</citation>
    <PMID>21680794</PMID>
  </reference>
  <reference>
    <citation>Stein R, Balkman C, Chen S, Rassnick K, McEntee M, Page R, Goldenberg DM. Evaluation of anti-human leukocyte antigen-DR monoclonal antibody therapy in spontaneous canine lymphoma. Leuk Lymphoma. 2011 Feb;52(2):273-84. doi: 10.3109/10428194.2010.535182. Epub 2010 Dec 6.</citation>
    <PMID>21133722</PMID>
  </reference>
  <reference>
    <citation>Stein R, Gupta P, Chen X, Cardillo TM, Furman RR, Chen S, Chang CH, Goldenberg DM. Therapy of B-cell malignancies by anti-HLA-DR humanized monoclonal antibody, IMMU-114, is mediated through hyperactivation of ERK and JNK MAP kinase signaling pathways. Blood. 2010 Jun 24;115(25):5180-90. doi: 10.1182/blood-2009-06-228288. Epub 2010 Jan 25.</citation>
    <PMID>20101022</PMID>
  </reference>
  <verification_date>March 2020</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>August 12, 2021</last_update_submitted>
  <last_update_submitted_qc>August 12, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 19, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>NHL</keyword>
  <keyword>CLL</keyword>
  <keyword>follicular lymphoma</keyword>
  <keyword>mantle cell lymphoma</keyword>
  <keyword>marginal zone lymphoma</keyword>
  <keyword>chronic lymphocytic leukemia</keyword>
  <keyword>small lymphocytic lymphoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Lymphoma, Follicular</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
    <mesh_term>Leukemia, Lymphoid</mesh_term>
    <mesh_term>Leukemia, Lymphocytic, Chronic, B-Cell</mesh_term>
    <mesh_term>Lymphoma, Mantle-Cell</mesh_term>
    <mesh_term>Lymphoma, B-Cell, Marginal Zone</mesh_term>
  </condition_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/NCT01728207
org study id: IMMU-114-01
nct id: NCT01728207
lead sponsor: 
has dmc: No
IMMU-114 will be studied at different dose schedules and dose levels in order to assess the
      highest dose safely tolerated. IMMU-114 will be administered subcutaneously (under the skin).
      IMMU-114 will be given 1-2 times weekly for 3 weeks followed by one week of rest. This is
      considered one cycle. Treatment cycles will be repeated until toxicity or worsening of
      disease.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
time frame: Safety will be assessed by measuring the change from baseline during treatment and up to 30 days after treatment
description: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
measure: Clinical Response: o Measured by International Working Group Criteria for NHL patients. o Measured by IWCLL 2008 Guidelines for CLL patients.
time frame: Efficacy will be assessed every 12 weeks during treatment and 4 weeks after the end of treatment
description: Responders will be defined as those with complete response (CR) or partial response (PR). Overall response rate (ORR) will be calculated as the number of evaluable responders divided by the total number of evaluable patients.
measure: Progression Free Survival
time frame: During treatment and the changes at 4, 8 and 12 weeks after treatment and then every 3 months for up to 2 years
measure: Overall Survival
time frame: During treatment and the changes at 4, 8 and 12 weeks after treatment and then every 3 months for up to 2 years
arm group label: IMMU-114
arm group type: Experimental
description: IMMU-114 will be administered subcutaneously (under the skin) once or twice weekly for 3 weeks followed by one week of rest. Treatment cycles will continue until disease worsening or toxicity. Various dose levels will be studied.
intervention type: Drug
intervention name: IMMU-114
description: hL243 is a humanized antibody that targets HLA-DR, which is found on various b-cell hematologic malignancies and in autoimmune diseases.
arm group label: IMMU-114
other name: hL243
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: William Wegener, MD, PhD
role: Study Chair
affiliation: Gilead Sciences
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
citation: Park KH, Sawada T, Murakami T, Ishii Y, Yasuo M, Fuchinoue S, Goldenberg DM, Kubota K. Anti-class II -DR humanized monoclonal antibody, IMMU-114, blocks allogeneic immune response. Am J Surg. 2012 Oct;204(4):527-34. doi: 10.1016/j.amjsurg.2011.11.017. Epub 2012 Jun 1.
PMID: 22658578
citation: Chen X, Chang CH, Stein R, Goldenberg DM. The humanized anti-HLA-DR moAb, IMMU-114, depletes APCs and reduces alloreactive T cells: implications for preventing GVHD. Bone Marrow Transplant. 2012 Jul;47(7):967-80. doi: 10.1038/bmt.2011.203. Epub 2011 Oct 24.
PMID: 22020022
citation: Rossi EA, Rossi DL, Cardillo TM, Stein R, Goldenberg DM, Chang CH. Preclinical studies on targeted delivery of multiple IFNalpha2b to HLA-DR in diverse hematologic cancers. Blood. 2011 Aug 18;118(7):1877-84. doi: 10.1182/blood-2011-03-343145. Epub 2011 Jun 16.
PMID: 21680794
citation: Stein R, Balkman C, Chen S, Rassnick K, McEntee M, Page R, Goldenberg DM. Evaluation of anti-human leukocyte antigen-DR monoclonal antibody therapy in spontaneous canine lymphoma. Leuk Lymphoma. 2011 Feb;52(2):273-84. doi: 10.3109/10428194.2010.535182. Epub 2010 Dec 6.
PMID: 21133722
citation: Stein R, Gupta P, Chen X, Cardillo TM, Furman RR, Chen S, Chang CH, Goldenberg DM. Therapy of B-cell malignancies by anti-HLA-DR humanized monoclonal antibody, IMMU-114, is mediated through hyperactivation of ERK and JNK MAP kinase signaling pathways. Blood. 2010 Jun 24;115(25):5180-90. doi: 10.1182/blood-2009-06-228288. Epub 2010 Jan 25.
PMID: 20101022
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Leukemia
mesh term: Lymphoma, Follicular
mesh term: Lymphoma, Non-Hodgkin
mesh term: Leukemia, Lymphoid
mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
mesh term: Lymphoma, Mantle-Cell
mesh term: Lymphoma, B-Cell, Marginal Zone