<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/NCT01663766</url>
  </required_header>
  <id_info>
    <org_study_id>IM-T-IMMU-115-03</org_study_id>
    <nct_id>NCT01663766</nct_id>
  </id_info>
  <brief_title>Phase I Study of Milatuzumab for Graft Versus Host Disease</brief_title>
  <official_title>A Phase I Study of Milatuzumab (hLL1) for Prevention of Acute Graft Versus Host Disease Following Reduced-Intensity Conditioning Allogeneic Stem Cell Transplant in Patients With Hematologic Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gilead Sciences</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ohio State University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Gilead Sciences</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will assess the safety and tolerability of milatuzumab (IMMU-115) when added to a&#xD;
      standard regimen to prevent Graft vs. Host Disease (GVHD) in patients with hematologic&#xD;
      malignancies undergoing stem cell transplant.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    PIs agreed no safety signals were shown, drug did not appear to lessen the risk of preventing&#xD;
    GVHD no further patients would be enrolled&#xD;
  </why_stopped>
  <start_date type="Actual">December 2013</start_date>
  <completion_date type="Actual">March 2015</completion_date>
  <primary_completion_date type="Actual">March 2015</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>All patients administered any dose of study drug will be included in the evaluation of safety</measure>
    <time_frame>Safety will be assessed by measuring the change from baseline during 7 days of treatment and up to 30 days after treatment</time_frame>
    <description>Safety will be measured by physical examinations and hematology and chemistry blood tests. Cardiac safety will be done using MUGA scans or echocardiograms. These assessments will be done routinely during treatment and up to 30 days after treatment and any change from baseline will be assessed. Long term safety will be assessed every 3 months after that for up to 1 year; any change from baseline will be assessed.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Determine the therapeutic efficacy of milatuzumab in this patient population</measure>
    <time_frame>Efficacy will be assessed 30 days after treatment.</time_frame>
    <description>Acute GVHD will be assessed at days +30 and +100 by laboratory testing. Chronic GVHD assessment will be performed at days +100, +270 &amp; +365 after stem cell transplant.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>GVHD (Acute or Chronic)</condition>
  <condition>Acute Myeloid or Lymphoblastic Leukemia (AML or ALL)</condition>
  <condition>Myelodysplastic Syndrome</condition>
  <condition>Chronic Myelogenous Leukemia (CML)</condition>
  <condition>Multiple Myeloma (MM)</condition>
  <condition>Non-Hodgekin Lymphoma (NHL-both Follicular &amp; Diffuse Large Cell)</condition>
  <condition>Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia (CLL or SLL)</condition>
  <arm_group>
    <arm_group_label>Milatuzumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Milatuzumab will be added to the standard GVHD reduced intensity consitioning and prophylaxis regimen of fludarabine, busulfan, tacrolimus and low-dose methotrexate.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>milatuzumab</intervention_name>
    <description>Milatuzumab is a humanized anti-CD74 antibody that is administered intravenously.</description>
    <arm_group_label>Milatuzumab</arm_group_label>
    <other_name>IMMU-115</other_name>
    <other_name>hLL1</other_name>
    <other_name>anti-CD74</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males or non-pregnant, non-lactating females, ≥ 18 years of age&#xD;
&#xD;
          -  Able to understand and willing to sign informed consent.&#xD;
&#xD;
          -  Histologically confirmed hematologic malignancy that is deemed best treated by RIC&#xD;
             allogeneic SCT, including:&#xD;
&#xD;
          -  Acute myeloid or lymphoblastic leukemia (AML, ALL) with &lt; 5% blasts in the bone marrow&#xD;
&#xD;
          -  Myelodysplastic syndrome and intermediate-2 or high-risk IPSS score with &lt; 5% blasts&#xD;
             in the bone marrow&#xD;
&#xD;
          -  Chronic myelogenous leukemia failing to respond to at least two different tyrosine&#xD;
             kinase inhibitors&#xD;
&#xD;
          -  Multiple myeloma that has relapsed following autologous stem cell transplant&#xD;
&#xD;
          -  Follicular lymphoma (grades 1, 2, or 3a by WHO criteria) or monocytoid lymphoma that&#xD;
             has relapsed following at least two prior chemotherapy regimens and with either no&#xD;
             lymph node groups ≥ 3 cm or with a ≥ 50% reduction in estimated lymph node diameter&#xD;
             with most recent salvage therapy&#xD;
&#xD;
          -  Diffuse large B-cell NHL that has relapsed after at least 2 prior chemotherapy&#xD;
             regimens (could include high-dose chemotherapy with autologous stem cell rescue) and&#xD;
             is still sensitive to chemotherapy by virtue of a PR or CR following most recent&#xD;
             salvage chemotherapy&#xD;
&#xD;
          -  Transformed follicular lymphoma that has achieved a PR or CR following chemotherapy&#xD;
&#xD;
          -  Mantle cell lymphoma that has relapsed after at least 2 prior chemotherapy regimens&#xD;
             (could include high-dose chemotherapy with autologous stem cell rescue)&#xD;
&#xD;
          -  CLL/SLL/PLL that meets one of the following:&#xD;
&#xD;
          -  del (17p13.1) in first remission&#xD;
&#xD;
          -  Response no better than a PR with chemoimmunotherapy or relapse within 2 years of&#xD;
             chemoimmunotherapy&#xD;
&#xD;
          -  Richter's transformation&#xD;
&#xD;
          -  Complex karyotype&#xD;
&#xD;
          -  At least 4 weeks beyond prior chemotherapy (excluding steroids), antibody therapy,&#xD;
             radiation, or radioimmunoconjugate therapy, and with any kinase inhibitors&#xD;
             discontinued at least one week prior to starting the conditioning regimen.&#xD;
&#xD;
          -  ECOG performance status ≤ 2&#xD;
&#xD;
          -  Life expectancy of greater than 3 months&#xD;
&#xD;
          -  Adequate organ function measured by the following within seven days of beginning&#xD;
             conditioning:&#xD;
&#xD;
          -  AST (SGOT) ≤ 3.0 x institutional upper limit of normal (IULN)&#xD;
&#xD;
          -  Total bilirubin ≤ 1.5 xIULN unless due to Gilbert's disease&#xD;
&#xD;
          -  Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 50 mL/min&#xD;
&#xD;
          -  DLCO &gt; 40% with no symptomatic pulmonary disease&#xD;
&#xD;
          -  LVEF by echocardiogram or MUGA of at least 30%&#xD;
&#xD;
          -  Women of child bearing potential and men must agree to use contraception prior to&#xD;
             study entry and for the duration of study participation.&#xD;
&#xD;
          -  Matched (8/8) related or matched unrelated donor identified. Haploidentical or&#xD;
             umbilical cord grafts are not allowed.&#xD;
&#xD;
          -  Donor willing to donate peripheral blood stem cells and meets institutional criteria&#xD;
             for stem cell donation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior allogeneic stem cell transplant&#xD;
&#xD;
          -  Patients requiring a myeloablative conditioning regimen&#xD;
&#xD;
          -  Patients best served by a bone marrow transplant are not eligible as this study will&#xD;
             be restricted only to peripheral stem cells.&#xD;
&#xD;
          -  No suitable donor identified&#xD;
&#xD;
          -  Prior anaphylactic response or Grade 4 infusion reaction to milatuzumab&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including but not limited to ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements.&#xD;
&#xD;
          -  Patients with active hepatitis B infection are not eligible. Patients with a history&#xD;
             of hepatitis B (surface antigen or core antibody positive) must take lamivudine or&#xD;
             equivalent during study therapy and for one year after completion of milatuzumab.&#xD;
&#xD;
          -  LVEF &lt; 30%&#xD;
&#xD;
          -  Seropositivity for HIV or Hepatitis C&#xD;
&#xD;
          -  Patients with known CNS lymphoma are excluded because of their poor prognosis and&#xD;
             because they often develop progressive neurologic dysfunction that would confound the&#xD;
             evaluation of neurologic and other adverse events.&#xD;
&#xD;
          -  Active secondary malignancies with the exception of non-melanomatous skin cancers or&#xD;
             low risk prostate cancer under observation.&#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>Ohio State University Comprehensive Cancer Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>August 7, 2012</study_first_submitted>
  <study_first_submitted_qc>August 9, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 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>GVHD (acute or chronic)</keyword>
  <keyword>acute myeloid or lymphoblastic leukemia (AML or ALL)</keyword>
  <keyword>myelodysplastic syndrome</keyword>
  <keyword>Chronic myelogenous leukemia (CML)</keyword>
  <keyword>Multiple Myeloma (MM)</keyword>
  <keyword>Non-Hodgekin lymphoma (NHL-both follicular &amp; diffuse large cell)</keyword>
  <keyword>Chronic lymphocytic leukemia or small lymphocytic leukemia (CLL or SLL)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
    <mesh_term>Preleukemia</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Leukemia, Lymphoid</mesh_term>
    <mesh_term>Leukemia, Lymphocytic, Chronic, B-Cell</mesh_term>
    <mesh_term>Leukemia, Myeloid</mesh_term>
    <mesh_term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive</mesh_term>
    <mesh_term>Myelodysplastic Syndromes</mesh_term>
    <mesh_term>Graft vs Host Disease</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/NCT01663766
org study id: IM-T-IMMU-115-03
nct id: NCT01663766
lead sponsor: 
collaborator: 
has dmc: No
This study will assess the safety and tolerability of milatuzumab (IMMU-115) when added to a
      standard regimen to prevent Graft vs. Host Disease (GVHD) in patients with hematologic
      malignancies undergoing stem cell transplant.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: All patients administered any dose of study drug will be included in the evaluation of safety
time frame: Safety will be assessed by measuring the change from baseline during 7 days of treatment and up to 30 days after treatment
description: Safety will be measured by physical examinations and hematology and chemistry blood tests. Cardiac safety will be done using MUGA scans or echocardiograms. These assessments will be done routinely during treatment and up to 30 days after treatment and any change from baseline will be assessed. Long term safety will be assessed every 3 months after that for up to 1 year; any change from baseline will be assessed.
measure: Determine the therapeutic efficacy of milatuzumab in this patient population
time frame: Efficacy will be assessed 30 days after treatment.
description: Acute GVHD will be assessed at days +30 and +100 by laboratory testing. Chronic GVHD assessment will be performed at days +100, +270 & +365 after stem cell transplant.
arm group label: Milatuzumab
arm group type: Experimental
description: Milatuzumab will be added to the standard GVHD reduced intensity consitioning and prophylaxis regimen of fludarabine, busulfan, tacrolimus and low-dose methotrexate.
intervention type: Drug
intervention name: milatuzumab
description: Milatuzumab is a humanized anti-CD74 antibody that is administered intravenously.
arm group label: Milatuzumab
other name: IMMU-115
other name: hLL1
other name: anti-CD74
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: 
country: United States
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Preleukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Lymphoid
mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myelogenous, Chronic, BCR-ABL Positive
mesh term: Myelodysplastic Syndromes
mesh term: Graft vs Host Disease