<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/NCT04438382</url>
  </required_header>
  <id_info>
    <org_study_id>EAQ172</org_study_id>
    <secondary_id>NCI-2018-02825</secondary_id>
    <secondary_id>EAQ172</secondary_id>
    <secondary_id>ECOG-ACRIN-EAQ172</secondary_id>
    <secondary_id>ECOG-ACRIN-EAQ172</secondary_id>
    <secondary_id>UG1CA189828</secondary_id>
    <nct_id>NCT04438382</nct_id>
  </id_info>
  <brief_title>Infliximab and Intravenous Immunoglobulin Therapy in Treating Patients With Steroid-Refractory Pneumonitis</brief_title>
  <official_title>Optimizing Immunosuppression for Steroid-Refractory Anti-PD-1/PD-L1 Pneumonitis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>ECOG-ACRIN Cancer Research Group</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Eastern Cooperative Oncology Group</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II trial studies how well infliximab and intravenous immunoglobulin therapy work&#xD;
      in treating patients with pneumonitis that does not respond to steroid treatment.&#xD;
      Immunotherapy with monoclonal antibodies such as, infliximab, may induce changes in body's&#xD;
      immune system and may interfere with the ability of tumor cells to grow and spread.&#xD;
      Intravenous immunoglobulin therapy may improve pneumonitis. It is not yet known whether&#xD;
      giving infliximab and intravenous immunoglobulin therapy will work better in treating&#xD;
      patients with pneumonitis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To assess pneumonitis response to additional immunosuppression (infliximab or intravenous&#xD;
      immunoglobulin therapy [IVIG]) in patients with steroid-refractory pneumonitis at 28-days.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To assess functional parameters of steroid-refractory pneumonitis at day 1, 14-days and&#xD;
      28-days after day 1 of receipt of additional immunosuppression (infliximab or IVIG).&#xD;
&#xD;
      II. To assess radiologic parameters of steroid-refractory pneumonitis at day 1, 14-days and&#xD;
      28-days after day 1 of receipt of additional immunosuppression (infliximab or IVIG).&#xD;
&#xD;
      III. To assess patient-reported outcomes of steroid-refractory pneumonitis at day 1, 14-days&#xD;
      and 28-days after day 1 of receipt of additional immunosuppression (infliximab or IVIG).&#xD;
&#xD;
      IV. To assess death after additional immunosuppression. V. To assess the rate of infections&#xD;
      in the 28-day period after additional immunosuppression.&#xD;
&#xD;
      EXPLORATORY OBJECTIVES:&#xD;
&#xD;
      I. To examine lung tissue, bronchoalveolar lavage (BAL) and serial blood samples in patients&#xD;
      who develop steroid-refractory pneumonitis.&#xD;
&#xD;
      II. To examine associations between BAL phenotypes and pneumonitis response, functional and&#xD;
      radiologic parameters of pneumonitis.&#xD;
&#xD;
      III. To evaluate associations between pneumonitis and autoantibodies, T-cell expansion, and&#xD;
      baseline cytokines in the blood.&#xD;
&#xD;
      OUTLINE: Patients are randomized to 1 of 2 arms.&#xD;
&#xD;
      ARM A: Patients receive infliximab intravenously (IV) on day 1 followed by prednisone taper&#xD;
      IV or orally (PO) for 4-6 weeks in the absence of disease progression or unacceptable&#xD;
      toxicity. Patients may receive an additional dose of infliximab IV on day 14 at the&#xD;
      discretion of the treating physician.&#xD;
&#xD;
      ARM B: Patients receive intravenous immunoglobulin therapy IV over 2-5 days per institutional&#xD;
      guidelines followed by prednisone taper IV or PO for 4-6 weeks in the absence of disease&#xD;
      progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 28, 42 and 56 days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 7, 2021</start_date>
  <completion_date type="Anticipated">July 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">July 31, 2025</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pneumonitis response rate</measure>
    <time_frame>At day 28</time_frame>
    <description>Pneumonitis response will be defined as an improvement in partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) of &gt;= 20% measured by PaO2 and recording of the FiO2 received by the patient at the time of the arterial blood gas assessment, on day 28 compared with day 1. Response rate will be reported with a proportion and its 90% confidence interval for each treatment arm. A comparison on the pneumonitis response rate between the two arms (infliximab vs. intravenous immunoglobulin [IVIG]) will be performed using Fisher's exact test.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Radiologic parameters of steroid-refractory pneumonitis</measure>
    <time_frame>At days 1, 14, and 28</time_frame>
    <description>Radiologic features of steroid-refractory pneumonitis will be assessed by percentage lung parenchyma involved, percentage of ground-glass opacity in lung parenchyma, and lung volume on computed tomography. The pneumonitis and lung volume will be graded &quot;Definitely decreased&quot;, &quot;Probably decreased&quot;, &quot;No significant change&quot;, &quot;Probably increased&quot; and &quot;Definitely increased&quot;. Response to study therapy will be defined by combining the categories &quot;Definitely decreased&quot; and &quot;Probably decreased&quot;. The response rate will be compared between the arms using Fisher's exact test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional parameters of steroid-refractory pneumonitis by spirometry</measure>
    <time_frame>At days 1, 14, and 28</time_frame>
    <description>Functional features of pneumonitis will be assessed by spirometry (forced vital capacity, forced expiratory volume in one second). These quantitative measures will be reported descriptively (by median, mean, and range) by timepoints and treatment arms. Pneumonitis improvement (from day 1 to day 14 and from day 1 to day 28) by each measure will be evaluated using the Wilcoxon signed-rank tests, by arm, without statistical adjustments.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional parameters of steroid-refractory pneumonitis by diffusion capacity</measure>
    <time_frame>At days 1, 14, and 28</time_frame>
    <description>Functional features of pneumonitis will be assessed by diffusion capacity of the lung. These quantitative measures will be reported descriptively (by median, mean, and range) by timepoints and treatment arms. Pneumonitis improvement (from day 1 to day 14 and from day 1 to day 28) by each measure will be evaluated using the Wilcoxon signed-rank tests, by arm, without statistical adjustments.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional parameters of steroid-refractory pneumonitis by oxygen saturation</measure>
    <time_frame>At days 1, 14, and 28</time_frame>
    <description>Functional features of pneumonitis will be assessed by oxygen saturation on room air at rest, collected as part of the vital signs. These quantitative measures will be reported descriptively (by median, mean, and range) by timepoints and treatment arms. Pneumonitis improvement (from day 1 to day 14 and from day 1 to day 28) by each measure will be evaluated using the Wilcoxon signed-rank tests, by arm, without statistical adjustments.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of reported deaths</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Death reported in the 28-day period will be tabulated by treatment arm, and classified as pneumonitis-related, immunosuppression related, disease-related or other.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The number and severity of treatment-related adverse events from infections in any organ system by the CTCAE reported in the 28-day period after additional immunosuppression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient-reported outcomes of steroid-refractory pneumonitis</measure>
    <time_frame>At days 1, 14, and 28</time_frame>
    <description>Patient-reported outcomes of steroid-refractory pneumonitis will be measured by questionnaires (Functional Assessment of Cancer Therapy - Lung version 4) and the Borg scale). Functional Assessment of Cancer Therapy - Lung consists of 5 subscales and each subscale score will be computed separately. These quantitative measures will be reported descriptively (by median, mean, and range) by timepoints and treatment arms. Pneumonitis improvement (from day 1 to day 14 and from day 1 to day 28) by each measure will be evaluated using the Wilcoxon signed-rank tests, by arm, without statistical adjustments.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Assessment of features and phenotypic parameters</measure>
    <time_frame>At baseline</time_frame>
    <description>Biospecimens from lung tissue and bronchoscopy will be collected to describe individual features and phenotypes from bronchoalveolar lavage (BAL) and lung tissue, respectively, using summary statistics (median/range or frequency/proportion where appropriate).</description>
  </other_outcome>
  <other_outcome>
    <measure>Biomarker analysis</measure>
    <time_frame>On days 1, 14, and 28 post-treatment</time_frame>
    <description>Potential blood/serum biomarkers for pneumonitis will be assessed from serially collected blood/serum in accrued patients and controls, whose blood/serum will be obtained as part of a parallel tissue-collection protocol. Autoantibodies, T-cell expansions (negative/positive), and cytokine levels (e.g., IFN-gamma, IL-17, and VEG-F) will be summarized descriptively in patients with pneumonitis vs. controls, by time point and treatment arm (when appropriate). Fisher's exact test will be used to evaluate associations of pneumonitis (yes/no) with autoantibodies, T-cell expansions (negative/positive), and baseline cytokines (dichotomized by the median of each cytokine). The association of BAL phenotype with pneumonitis response (yes/no), functional and radiologic parameters of pneumonitis will be evaluated using Fisher's exact test or logistic regressions, where appropriate.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">36</enrollment>
  <condition>Hematopoietic and Lymphoid Cell Neoplasm</condition>
  <condition>Malignant Solid Neoplasm</condition>
  <condition>Steroid-Refractory Pneumonitis</condition>
  <arm_group>
    <arm_group_label>Arm A (infliximab)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive infliximab IV on day 1 followed by prednisone taper IV or PO for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Patients may receive an additional dose of infliximab IV on day 14 at the discretion of the treating physician.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B (intravenous immunoglobulin therapy)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive intravenous immunoglobulin therapy IV over 2-5 days per institutional guidelines followed by prednisone taper IV or PO for 4-6 weeks in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Infliximab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm A (infliximab)</arm_group_label>
    <other_name>Avakine</other_name>
    <other_name>cA2</other_name>
    <other_name>Remicade</other_name>
    <other_name>Remsima</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Intravenous Immunoglobulin Therapy</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm B (intravenous immunoglobulin therapy)</arm_group_label>
    <other_name>Gamma Globulin</other_name>
    <other_name>Gamma Globulin Therapy</other_name>
    <other_name>Immune Globulin</other_name>
    <other_name>Immune Globulin Therapy</other_name>
    <other_name>Intravenous Immunoglobulin</other_name>
    <other_name>IVIG</other_name>
    <other_name>IVIG Therapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prednisone</intervention_name>
    <description>Given IV or PO</description>
    <arm_group_label>Arm A (infliximab)</arm_group_label>
    <arm_group_label>Arm B (intravenous immunoglobulin therapy)</arm_group_label>
    <other_name>.delta.1-Cortisone</other_name>
    <other_name>1, 2-Dehydrocortisone</other_name>
    <other_name>Adasone</other_name>
    <other_name>Cortancyl</other_name>
    <other_name>Dacortin</other_name>
    <other_name>DeCortin</other_name>
    <other_name>Decortisyl</other_name>
    <other_name>Decorton</other_name>
    <other_name>Delta 1-Cortisone</other_name>
    <other_name>Delta-Dome</other_name>
    <other_name>Deltacortene</other_name>
    <other_name>Deltacortisone</other_name>
    <other_name>Deltadehydrocortisone</other_name>
    <other_name>Deltasone</other_name>
    <other_name>Deltison</other_name>
    <other_name>Deltra</other_name>
    <other_name>Econosone</other_name>
    <other_name>Lisacort</other_name>
    <other_name>Meprosona-F</other_name>
    <other_name>Metacortandracin</other_name>
    <other_name>Meticorten</other_name>
    <other_name>Ofisolona</other_name>
    <other_name>Orasone</other_name>
    <other_name>Panafcort</other_name>
    <other_name>Panasol-S</other_name>
    <other_name>Paracort</other_name>
    <other_name>Perrigo Prednisone</other_name>
    <other_name>PRED</other_name>
    <other_name>Predicor</other_name>
    <other_name>Predicorten</other_name>
    <other_name>Prednicen-M</other_name>
    <other_name>Prednicort</other_name>
    <other_name>Prednidib</other_name>
    <other_name>Prednilonga</other_name>
    <other_name>Predniment</other_name>
    <other_name>Prednisone Intensol</other_name>
    <other_name>Prednisonum</other_name>
    <other_name>Prednitone</other_name>
    <other_name>Promifen</other_name>
    <other_name>Rayos</other_name>
    <other_name>Servisone</other_name>
    <other_name>SK-Prednisone</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Quality-of-Life Assessment</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Arm A (infliximab)</arm_group_label>
    <arm_group_label>Arm B (intravenous immunoglobulin therapy)</arm_group_label>
    <other_name>Quality of Life Assessment</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Questionnaire Administration</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Arm A (infliximab)</arm_group_label>
    <arm_group_label>Arm B (intravenous immunoglobulin therapy)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must be English-speaking and be able to provide informed consent&#xD;
&#xD;
          -  Patient must be willing and able to undergo arterial blood gas assessment as per the&#xD;
             treating investigator. Patient must not have contraindication for arterial blood gas&#xD;
             assessment&#xD;
&#xD;
          -  Women must not be pregnant or breast-feeding due to the potential risk to the fetus of&#xD;
             infliximab or IVIG. All females of childbearing potential must have a blood test or&#xD;
             urine test within 14 days prior to randomization to rule out pregnancy. A female of&#xD;
             childbearing potential is any woman, regardless of sexual orientation or whether they&#xD;
             have undergone tubal ligation, who meets the following criteria: 1) has achieved&#xD;
             menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy;&#xD;
             or 3) has not been naturally postmenopausal for at least 24 consecutive months (i.e.,&#xD;
             has had menses at any time in the preceding 24 consecutive months).&#xD;
&#xD;
          -  Women of childbearing potential and sexually active males must be strongly advised to&#xD;
             use an accepted and effective method(s) of contraception or to abstain from sexual&#xD;
             intercourse for a minimum of 56 days (the duration of their participation in the&#xD;
             study)&#xD;
&#xD;
          -  Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of&#xD;
             0-3&#xD;
&#xD;
          -  Patient may have received any number of lines of prior systemic therapy&#xD;
&#xD;
          -  Patient may have any solid tumor or hematologic malignancy is eligible&#xD;
&#xD;
          -  Patient must have received treatment with an anti-PD-1/PD-L1 agent either alone or in&#xD;
             combination with another anti-cancer agent, as their most recent therapy prior to&#xD;
             development of pneumonitis&#xD;
&#xD;
          -  Patient must have steroid-refractory pneumonitis defined as:&#xD;
&#xD;
               -  Grade 2 pneumonitis that has not clinically improved by a Common Terminology&#xD;
                  Criteria for Adverse Events (CTCAE) grade in greater than 72 hours or maximum of&#xD;
                  14 days or&#xD;
&#xD;
               -  Grade 3 or higher pneumonitis that has not clinically improved by a CTCAE grade&#xD;
                  in greater than 48 hours or maximum of 14 days with high dose corticosteroids&#xD;
                  (methylprednisolone or prednisone 1-4 mg/kg/equivalent) as their most recent&#xD;
                  treatment for pneumonitis, as determined by the treating investigator&#xD;
&#xD;
          -  Patient may have received anti-PD-1/PD-L1 therapy as standard-of-care or part of a&#xD;
             clinical trial&#xD;
&#xD;
          -  Patient must have had pathogen-negative infectious diagnostic evaluation within 14&#xD;
             days prior to randomization, and at a minimum these should include: blood culture,&#xD;
             urine culture, sputum culture, and viral panel: rapid flu, respiratory syncytial virus&#xD;
             (RSV), herpes simplex virus (HSV). Empiric antibiotics for culture negative infections&#xD;
             are not an exclusion for study entry&#xD;
&#xD;
          -  Patient must have had a pathogen-negative bronchoscopic assessment of BAL fluid within&#xD;
             14 days prior to randomization. A minimum assessment for pathogens on BAL must&#xD;
             include: gram stain, fungal panel, viral panel&#xD;
&#xD;
          -  Patient must have a negative tuberculosis assessment (TB spot test, quantiferon gold&#xD;
             or tuberculin skin test) within 14 days prior to randomization&#xD;
&#xD;
          -  Patient must have chest computed tomography (CT) scan without contrast performed =&lt; 14&#xD;
             days before randomization. Patient must not have a contraindication for CT&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient must not have clinical evidence of cardiac dysfunction (as determined by the&#xD;
             treating investigator) as an alternative diagnosis to steroid-refractory pneumonitis&#xD;
&#xD;
          -  Patient must not be receiving anti-PD-1/-PD-L1 agent in combination with any of the&#xD;
             following anti-cancer agents: docetaxel, cyclophosphamide, gefitinib, erlotinib,&#xD;
             osimertinib, crizotinib, bleomycin, afatinib&#xD;
&#xD;
          -  Patient must not be receiving concurrent radiation therapy to the chest&#xD;
&#xD;
          -  Patient must not be deemed to have radiation pneumonitis. Patients with a history of&#xD;
             stable radiation pneumonitis not requiring corticosteroid therapy within the last 3&#xD;
             months prior to randomization will be allowed on study&#xD;
&#xD;
          -  Patient must not have pre-existing interstitial lung disease or pneumonitis requiring&#xD;
             corticosteroid therapy from any other cause, as determined by the treating&#xD;
             investigator&#xD;
&#xD;
          -  Patient must not have an absolute contraindication to IVIG or infliximab, including:&#xD;
             clinical history of severe hypersensitivity reaction, selective IgA deficiency, active&#xD;
             hepatitis B, active tuberculosis, active human immunodeficiency virus/acquired&#xD;
             immunodeficiency syndrome (HIV/AIDS) where a study subject has a CD4 count of =&lt; 200&#xD;
             at screening, or drug interaction&#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>Jarushka Naidoo</last_name>
    <role>Principal Investigator</role>
    <affiliation>ECOG-ACRIN Cancer Research Group</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>312-695-1301</phone>
      <email>cancer@northwestern.edu</email>
    </contact>
    <investigator>
      <last_name>Sheetal M. Kircher</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins University/Sidney Kimmel Cancer Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>410-955-8804</phone>
      <email>jhcccro@jhmi.edu</email>
    </contact>
    <investigator>
      <last_name>Julie R. Brahmer</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Bronson Battle Creek</name>
      <address>
        <city>Battle Creek</city>
        <state>Michigan</state>
        <zip>49017</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>616-391-1230</phone>
      <email>crcwm-regulatory@crcwm.org</email>
    </contact>
    <investigator>
      <last_name>Kathleen J. Yost</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Mercy Health Saint Mary's</name>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49503</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>616-391-1230</phone>
      <email>crcwm-regulatory@crcwm.org</email>
    </contact>
    <investigator>
      <last_name>Kathleen J. Yost</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Spectrum Health at Butterworth Campus</name>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49503</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>616-391-1230</phone>
      <email>crcwm-regulatory@crcwm.org</email>
    </contact>
    <investigator>
      <last_name>Kathleen J. Yost</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>West Michigan Cancer Center</name>
      <address>
        <city>Kalamazoo</city>
        <state>Michigan</state>
        <zip>49007</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>616-391-1230</phone>
      <email>crcwm-regulatory@crcwm.org</email>
    </contact>
    <investigator>
      <last_name>Kathleen J. Yost</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Mercy Health Mercy Campus</name>
      <address>
        <city>Muskegon</city>
        <state>Michigan</state>
        <zip>49444</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>616-391-1230</phone>
      <email>crcwm-regulatory@crcwm.org</email>
    </contact>
    <investigator>
      <last_name>Kathleen J. Yost</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Lakeland Hospital Niles</name>
      <address>
        <city>Niles</city>
        <state>Michigan</state>
        <zip>49120</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>616-391-1230</phone>
    </contact>
    <investigator>
      <last_name>Kathleen J. Yost</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Cancer and Hematology Centers of Western Michigan - Norton Shores</name>
      <address>
        <city>Norton Shores</city>
        <state>Michigan</state>
        <zip>49444</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>616-391-1230</phone>
      <email>connie.szczepanek@crcwm.org</email>
    </contact>
    <investigator>
      <last_name>Kathleen J. Yost</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Spectrum Health Reed City Hospital</name>
      <address>
        <city>Reed City</city>
        <state>Michigan</state>
        <zip>49677</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>616-391-1230</phone>
      <email>crcwm-regulatory@crcwm.org</email>
    </contact>
    <investigator>
      <last_name>Kathleen J. Yost</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Lakeland Medical Center Saint Joseph</name>
      <address>
        <city>Saint Joseph</city>
        <state>Michigan</state>
        <zip>49085</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>616-391-1230</phone>
      <email>crcwm-regulatory@crcwm.org</email>
    </contact>
    <investigator>
      <last_name>Kathleen J. Yost</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Marie Yeager Cancer Center</name>
      <address>
        <city>Saint Joseph</city>
        <state>Michigan</state>
        <zip>49085</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>616-391-1230</phone>
      <email>crcwm-regulatory@crcwm.org</email>
    </contact>
    <investigator>
      <last_name>Kathleen J. Yost</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Munson Medical Center</name>
      <address>
        <city>Traverse City</city>
        <state>Michigan</state>
        <zip>49684</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>616-391-1230</phone>
      <email>crcwm-regulatory@crcwm.org</email>
    </contact>
    <investigator>
      <last_name>Kathleen J. Yost</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Metro Health Hospital</name>
      <address>
        <city>Wyoming</city>
        <state>Michigan</state>
        <zip>49519</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>616-391-1230</phone>
      <email>crcwm-regulatory@crcwm.org</email>
    </contact>
    <investigator>
      <last_name>Kathleen J. Yost</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>212-639-7592</phone>
    </contact>
    <investigator>
      <last_name>Jason Beattie</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Fox Chase Cancer Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19111</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>215-728-4790</phone>
    </contact>
    <investigator>
      <last_name>Christopher Manley</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>VCU Massey Cancer Center at Stony Point</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23235</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <email>ctoclinops@vcu.edu</email>
    </contact>
    <investigator>
      <last_name>Andrew Poklepovic</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Virginia Commonwealth University/Massey Cancer Center</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23298</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <email>CTOclinops@vcu.edu</email>
    </contact>
    <investigator>
      <last_name>Andrew Poklepovic</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>June 9, 2020</study_first_submitted>
  <study_first_submitted_qc>June 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 18, 2020</study_first_posted>
  <last_update_submitted>June 21, 2023</last_update_submitted>
  <last_update_submitted_qc>June 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pneumonia</mesh_term>
    <mesh_term>Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prednisone</mesh_term>
    <mesh_term>Infliximab</mesh_term>
    <mesh_term>Cortisone</mesh_term>
    <mesh_term>Immunoglobulins</mesh_term>
    <mesh_term>Immunoglobulins, Intravenous</mesh_term>
    <mesh_term>Antibodies</mesh_term>
    <mesh_term>gamma-Globulins</mesh_term>
    <mesh_term>Rho(D) Immune Globulin</mesh_term>
    <mesh_term>Immunoglobulin G</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/NCT04438382
org study id: EAQ172
secondary id: NCI-2018-02825
secondary id: EAQ172
secondary id: ECOG-ACRIN-EAQ172
secondary id: ECOG-ACRIN-EAQ172
secondary id: UG1CA189828
nct id: NCT04438382
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This phase II trial studies how well infliximab and intravenous immunoglobulin therapy work
      in treating patients with pneumonitis that does not respond to steroid treatment.
      Immunotherapy with monoclonal antibodies such as, infliximab, may induce changes in body's
      immune system and may interfere with the ability of tumor cells to grow and spread.
      Intravenous immunoglobulin therapy may improve pneumonitis. It is not yet known whether
      giving infliximab and intravenous immunoglobulin therapy will work better in treating
      patients with pneumonitis.
PRIMARY OBJECTIVE:

      I. To assess pneumonitis response to additional immunosuppression (infliximab or intravenous
      immunoglobulin therapy [IVIG]) in patients with steroid-refractory pneumonitis at 28-days.

      SECONDARY OBJECTIVES:

      I. To assess functional parameters of steroid-refractory pneumonitis at day 1, 14-days and
      28-days after day 1 of receipt of additional immunosuppression (infliximab or IVIG).

      II. To assess radiologic parameters of steroid-refractory pneumonitis at day 1, 14-days and
      28-days after day 1 of receipt of additional immunosuppression (infliximab or IVIG).

      III. To assess patient-reported outcomes of steroid-refractory pneumonitis at day 1, 14-days
      and 28-days after day 1 of receipt of additional immunosuppression (infliximab or IVIG).

      IV. To assess death after additional immunosuppression. V. To assess the rate of infections
      in the 28-day period after additional immunosuppression.

      EXPLORATORY OBJECTIVES:

      I. To examine lung tissue, bronchoalveolar lavage (BAL) and serial blood samples in patients
      who develop steroid-refractory pneumonitis.

      II. To examine associations between BAL phenotypes and pneumonitis response, functional and
      radiologic parameters of pneumonitis.

      III. To evaluate associations between pneumonitis and autoantibodies, T-cell expansion, and
      baseline cytokines in the blood.

      OUTLINE: Patients are randomized to 1 of 2 arms.

      ARM A: Patients receive infliximab intravenously (IV) on day 1 followed by prednisone taper
      IV or orally (PO) for 4-6 weeks in the absence of disease progression or unacceptable
      toxicity. Patients may receive an additional dose of infliximab IV on day 14 at the
      discretion of the treating physician.

      ARM B: Patients receive intravenous immunoglobulin therapy IV over 2-5 days per institutional
      guidelines followed by prednisone taper IV or PO for 4-6 weeks in the absence of disease
      progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 28, 42 and 56 days.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Pneumonitis response rate
time frame: At day 28
description: Pneumonitis response will be defined as an improvement in partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) of >= 20% measured by PaO2 and recording of the FiO2 received by the patient at the time of the arterial blood gas assessment, on day 28 compared with day 1. Response rate will be reported with a proportion and its 90% confidence interval for each treatment arm. A comparison on the pneumonitis response rate between the two arms (infliximab vs. intravenous immunoglobulin [IVIG]) will be performed using Fisher's exact test.
measure: Radiologic parameters of steroid-refractory pneumonitis
time frame: At days 1, 14, and 28
description: Radiologic features of steroid-refractory pneumonitis will be assessed by percentage lung parenchyma involved, percentage of ground-glass opacity in lung parenchyma, and lung volume on computed tomography. The pneumonitis and lung volume will be graded "Definitely decreased", "Probably decreased", "No significant change", "Probably increased" and "Definitely increased". Response to study therapy will be defined by combining the categories "Definitely decreased" and "Probably decreased". The response rate will be compared between the arms using Fisher's exact test.
measure: Functional parameters of steroid-refractory pneumonitis by spirometry
time frame: At days 1, 14, and 28
description: Functional features of pneumonitis will be assessed by spirometry (forced vital capacity, forced expiratory volume in one second). These quantitative measures will be reported descriptively (by median, mean, and range) by timepoints and treatment arms. Pneumonitis improvement (from day 1 to day 14 and from day 1 to day 28) by each measure will be evaluated using the Wilcoxon signed-rank tests, by arm, without statistical adjustments.
measure: Functional parameters of steroid-refractory pneumonitis by diffusion capacity
time frame: At days 1, 14, and 28
description: Functional features of pneumonitis will be assessed by diffusion capacity of the lung. These quantitative measures will be reported descriptively (by median, mean, and range) by timepoints and treatment arms. Pneumonitis improvement (from day 1 to day 14 and from day 1 to day 28) by each measure will be evaluated using the Wilcoxon signed-rank tests, by arm, without statistical adjustments.
measure: Functional parameters of steroid-refractory pneumonitis by oxygen saturation
time frame: At days 1, 14, and 28
description: Functional features of pneumonitis will be assessed by oxygen saturation on room air at rest, collected as part of the vital signs. These quantitative measures will be reported descriptively (by median, mean, and range) by timepoints and treatment arms. Pneumonitis improvement (from day 1 to day 14 and from day 1 to day 28) by each measure will be evaluated using the Wilcoxon signed-rank tests, by arm, without statistical adjustments.
measure: Number of reported deaths
time frame: Up to 28 days
description: Death reported in the 28-day period will be tabulated by treatment arm, and classified as pneumonitis-related, immunosuppression related, disease-related or other.
measure: Incidence of adverse events
time frame: Up to 28 days
description: Will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The number and severity of treatment-related adverse events from infections in any organ system by the CTCAE reported in the 28-day period after additional immunosuppression.
measure: Patient-reported outcomes of steroid-refractory pneumonitis
time frame: At days 1, 14, and 28
description: Patient-reported outcomes of steroid-refractory pneumonitis will be measured by questionnaires (Functional Assessment of Cancer Therapy - Lung version 4) and the Borg scale). Functional Assessment of Cancer Therapy - Lung consists of 5 subscales and each subscale score will be computed separately. These quantitative measures will be reported descriptively (by median, mean, and range) by timepoints and treatment arms. Pneumonitis improvement (from day 1 to day 14 and from day 1 to day 28) by each measure will be evaluated using the Wilcoxon signed-rank tests, by arm, without statistical adjustments.
measure: Assessment of features and phenotypic parameters
time frame: At baseline
description: Biospecimens from lung tissue and bronchoscopy will be collected to describe individual features and phenotypes from bronchoalveolar lavage (BAL) and lung tissue, respectively, using summary statistics (median/range or frequency/proportion where appropriate).
measure: Biomarker analysis
time frame: On days 1, 14, and 28 post-treatment
description: Potential blood/serum biomarkers for pneumonitis will be assessed from serially collected blood/serum in accrued patients and controls, whose blood/serum will be obtained as part of a parallel tissue-collection protocol. Autoantibodies, T-cell expansions (negative/positive), and cytokine levels (e.g., IFN-gamma, IL-17, and VEG-F) will be summarized descriptively in patients with pneumonitis vs. controls, by time point and treatment arm (when appropriate). Fisher's exact test will be used to evaluate associations of pneumonitis (yes/no) with autoantibodies, T-cell expansions (negative/positive), and baseline cytokines (dichotomized by the median of each cytokine). The association of BAL phenotype with pneumonitis response (yes/no), functional and radiologic parameters of pneumonitis will be evaluated using Fisher's exact test or logistic regressions, where appropriate.
arm group label: Arm A (infliximab)
arm group type: Experimental
description: Patients receive infliximab IV on day 1 followed by prednisone taper IV or PO for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Patients may receive an additional dose of infliximab IV on day 14 at the discretion of the treating physician.
arm group label: Arm B (intravenous immunoglobulin therapy)
arm group type: Experimental
description: Patients receive intravenous immunoglobulin therapy IV over 2-5 days per institutional guidelines followed by prednisone taper IV or PO for 4-6 weeks in the absence of disease progression or unacceptable toxicity.
intervention type: Biological
intervention name: Infliximab
description: Given IV
arm group label: Arm A (infliximab)
other name: Avakine
other name: cA2
other name: Remicade
other name: Remsima
intervention type: Biological
intervention name: Intravenous Immunoglobulin Therapy
description: Given IV
arm group label: Arm B (intravenous immunoglobulin therapy)
other name: Gamma Globulin
other name: Gamma Globulin Therapy
other name: Immune Globulin
other name: Immune Globulin Therapy
other name: Intravenous Immunoglobulin
other name: IVIG
other name: IVIG Therapy
intervention type: Drug
intervention name: Prednisone
description: Given IV or PO
arm group label: Arm A (infliximab)
arm group label: Arm B (intravenous immunoglobulin therapy)
other name: .delta.1-Cortisone
other name: 1, 2-Dehydrocortisone
other name: Adasone
other name: Cortancyl
other name: Dacortin
other name: DeCortin
other name: Decortisyl
other name: Decorton
other name: Delta 1-Cortisone
other name: Delta-Dome
other name: Deltacortene
other name: Deltacortisone
other name: Deltadehydrocortisone
other name: Deltasone
other name: Deltison
other name: Deltra
other name: Econosone
other name: Lisacort
other name: Meprosona-F
other name: Metacortandracin
other name: Meticorten
other name: Ofisolona
other name: Orasone
other name: Panafcort
other name: Panasol-S
other name: Paracort
other name: Perrigo Prednisone
other name: PRED
other name: Predicor
other name: Predicorten
other name: Prednicen-M
other name: Prednicort
other name: Prednidib
other name: Prednilonga
other name: Predniment
other name: Prednisone Intensol
other name: Prednisonum
other name: Prednitone
other name: Promifen
other name: Rayos
other name: Servisone
other name: SK-Prednisone
intervention type: Other
intervention name: Quality-of-Life Assessment
description: Ancillary studies
arm group label: Arm A (infliximab)
arm group label: Arm B (intravenous immunoglobulin therapy)
other name: Quality of Life Assessment
intervention type: Other
intervention name: Questionnaire Administration
description: Ancillary studies
arm group label: Arm A (infliximab)
arm group label: Arm B (intravenous immunoglobulin therapy)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jarushka Naidoo
role: Principal Investigator
affiliation: ECOG-ACRIN Cancer Research Group
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
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facility: 
status: Recruiting
contact: 
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facility: 
status: Recruiting
contact: 
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status: Recruiting
contact: 
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status: Recruiting
contact: 
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facility: 
status: Recruiting
contact: 
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status: Recruiting
contact: 
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status: Recruiting
contact: 
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status: Recruiting
contact: 
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facility: 
status: Recruiting
contact: 
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facility: 
status: Recruiting
contact: 
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facility: 
status: Recruiting
contact: 
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facility: 
status: Recruiting
contact: 
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status: Recruiting
contact: 
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facility: 
status: Recruiting
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facility: 
status: Recruiting
contact: 
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country: United States
responsible party type: Sponsor
mesh term: Pneumonia
mesh term: Neoplasms
mesh term: Prednisone
mesh term: Infliximab
mesh term: Cortisone
mesh term: Immunoglobulins
mesh term: Immunoglobulins, Intravenous
mesh term: Antibodies
mesh term: gamma-Globulins
mesh term: Rho(D) Immune Globulin
mesh term: Immunoglobulin G