<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/NCT04439006</url>
  </required_header>
  <id_info>
    <org_study_id>OSU-20135</org_study_id>
    <secondary_id>NCI-2020-03341</secondary_id>
    <nct_id>NCT04439006</nct_id>
  </id_info>
  <brief_title>Ibrutinib for the Treatment of COVID-19 in Patients Requiring Hospitalization</brief_title>
  <official_title>Randomized Double-Blind Phase 2 Trial of Ibrutinib Versus Standard Treatment for COVID-19 Illness Requiring Hospitalization With Safety Lead-In</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jennifer Woyach</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Janssen Scientific Affairs, LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Ohio State University Comprehensive Cancer Center</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase Ib/II trial studies the side effects and best dose of ibrutinib and how well it&#xD;
      works in treating patients with COVID-19 requiring hospitalization. Ibrutinib may help&#xD;
      improve COVID-19 symptoms by lessening the inflammatory response in the lungs, while&#xD;
      preserving overall immune function. This may reduce the need to be on a ventilator to help&#xD;
      with breathing.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the feasibility and tolerability of administering ibrutinib in COVID-19&#xD;
      infected patients and determining the recommended phase 2 dose (RP2D). (Phase Ib) II. To&#xD;
      determine whether ibrutinib administration (Arm A) in cancer patients can diminish the need&#xD;
      for artificial ventilation (mechanical ventilation, bilevel positive airway pressure [BiPAP]&#xD;
      or extracorporeal membrane oxygenation [ECMO]) or death due to COVID-19 as compared to&#xD;
      untreated control population receiving standard therapy (antiviral, chloroquine,&#xD;
      hydroxychloroquine, cytokine blocking peptides or small molecules) (Arm B). (Phase II)&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the time to defervescence (oral temperature &lt; 100.5 degrees Fahrenheit [F]&#xD;
      for a 48 hour time period) among patients treated with ibrutinib (Arm A) versus control&#xD;
      population receiving standard (Arm B) therapy.&#xD;
&#xD;
      II. To determine time to clinical resolution of need for supplemental oxygen (i.e.&#xD;
      maintenance of oxygen saturation of 93% or greater on room air with ambulation).&#xD;
&#xD;
      III. To determine rate of intensive care unit (ICU) admission and length of ICU admission for&#xD;
      patients treated with ibrutinib (Arm A) versus control population receiving standard therapy&#xD;
      (Arm B).&#xD;
&#xD;
      IV. To determine rate of shock requiring vasopressor support for patients treated with&#xD;
      ibrutinib (Arm A) versus control population receiving standard therapy (Arm B).&#xD;
&#xD;
      V. To determine the rate of secondary infection (bacterial, fungal, viral) for patients&#xD;
      treated with ibrutinib (Arm A) versus control population receiving standard therapy (Arm B).&#xD;
&#xD;
      VI. To determine the time to hospital discharge for patients treated with ibrutinib (Arm A)&#xD;
      versus control population receiving standard therapy (Arm B).&#xD;
&#xD;
      VII. To determine time to hospital discharge and rate of death for patients who cross over to&#xD;
      ibrutinib (Arm A) from standard therapy (Arm B).&#xD;
&#xD;
      VIII. To determine grade 3 or higher toxicity observed in patients treated with ibrutinib&#xD;
      (Arm A) versus control population receiving standard therapy (Arm B).&#xD;
&#xD;
      IX. To determine time to mechanical ventilation, the number of days of mechanical ventilation&#xD;
      per patient and total observed in patients treated with ibrutinib (Arm A) versus control&#xD;
      population receiving standard therapy (Arm B).&#xD;
&#xD;
      EXPLORATORY OBJECTIVES:&#xD;
&#xD;
      I. To examine the impact of baseline clinical features (e.g. type of cancer, active therapy),&#xD;
      duration of symptoms prior to admission and laboratory features (e.g. T cell count) on&#xD;
      outcome for patients treated on this therapeutic study.&#xD;
&#xD;
      II. To determine the proportion of patients with viral clearance at end of ibrutinib therapy,&#xD;
      time of hospital discharge and follow up thereafter among patients treated with ibrutinib&#xD;
      (Arm A) versus control (Arm B) treatment.&#xD;
&#xD;
      III. To determine the time and proportion of patients who develop immunoglobulin (Ig)M and&#xD;
      IgG levels toward SARS-coronavirus (CoV)-2 treated with ibrutinib (Arm A) versus control&#xD;
      treatment (Arm B).&#xD;
&#xD;
      IV. To examine immune cell subsets for absolute number, activation, exhaustion markers, and&#xD;
      presence of maturation arrest (natural killer [NK] cells) at baseline and over time among&#xD;
      patients treated with ibrutinib (Arm A) versus control (Arm B) treatment.&#xD;
&#xD;
      V. To examine T-cell repertoire over time among patients treated with ibrutinib (Arm A)&#xD;
      versus control (Arm B) treatment.&#xD;
&#xD;
      VI. To determine the influence of epigenetic age, clonal hematopoiesis, and monoclonal B cell&#xD;
      lymphocytosis (MBL) on treatment outcome.&#xD;
&#xD;
      VII. To determine serial change in inflammatory markers as CRP, ferritin, D-dimer and&#xD;
      cytokines including IL6, IL1B, and TNF-alpha serum levels over time among patients treated&#xD;
      with ibrutinib (Arm A) versus control (Arm B) treatment.&#xD;
&#xD;
      OUTLINE: This is a phase Ib, dose-escalation study followed by a phase II study.&#xD;
&#xD;
      The first 12 patients will all receive ibrutinib. In the randomized part, patients are&#xD;
      randomized to 1 of 2 arms.&#xD;
&#xD;
      ARM A: Patients receive ibrutinib orally (PO) once daily (QD) on days 1-7. Treatment repeats&#xD;
      every 7 days for 2 cycles in the absence of disease progression or unacceptable toxicity.&#xD;
      Patients who remain hospitalized or are re-admitted after 2 cycles may receive an additional&#xD;
      2 cycles per physician's discretion.&#xD;
&#xD;
      ARM B: Patients receive usual care. Patients who meet the requirement of mechanical&#xD;
      ventilation may cross-over to Arm A.&#xD;
&#xD;
      After completion of study treatment, patients are followed up for up to 12 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 23, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Actual">September 20, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <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>Proportion of patients with diminished respiratory failure and death</measure>
    <time_frame>During hospitalization for COVID-19 infection or within 30 days of registration</time_frame>
    <description>Associations between baseline characteristics and the primary endpoint will be evaluated with logistic regression, adjusting for arm. These analyses will be largely descriptive, as a result of a limited sample size.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Death</measure>
    <time_frame>During hospitalization for COVID-19 infection or within 30 days of registration</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time from study initiation to 48 hours fever-free</measure>
    <time_frame>Up to 14 days</time_frame>
    <description>Fever-free will be assessed by a temperature of &lt; 100.5 degrees Fahrenheit orally. Will be estimated for each arm using the method of Kaplan-Meier. Medians estimates and/or estimates at specific time points will be provided with 95% confidence intervals.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of hospitalization</measure>
    <time_frame>Up to 14 days</time_frame>
    <description>Will be estimated for each arm using the method of Kaplan-Meier. Medians estimates and/or estimates at specific time points will be provided with 95% confidence intervals.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time in intensive care unit (ICU)</measure>
    <time_frame>Up to 14 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to ICU admission</measure>
    <time_frame>Up to 14 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of days requiring supplemental oxygen</measure>
    <time_frame>Up to 14 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total days of mechanical ventilation</measure>
    <time_frame>Up to 14 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to mechanical ventilation</measure>
    <time_frame>Up to 14 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Shock and need for pressure support</measure>
    <time_frame>Up to 14 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of any infection (viral, fungal, bacterial)</measure>
    <time_frame>Up to 14 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to clinical resolution</measure>
    <time_frame>Up to 14 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of grade 3 or higher adverse events</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Adverse events will be summarized by grade, type, and attribution (regardless of attribution and treatment-related) for each arm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>At the end of therapy (day 14)</measure>
    <time_frame>Up to 14 days</time_frame>
    <description>The proportion of patients with viral clearance at the time of hospital discharge will be estimated with 95% confidence intervals for each arm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to viral clearance</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Will be estimated for each arm using the method of Kaplan-Meier. Medians estimates and/or estimates at specific time points will be provided with 95% confidence intervals.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival</measure>
    <time_frame>Up to12 months</time_frame>
    <description>Patients will be followed for up to 12 months or until death or withdrawal of study consent for further follow-up. Following hospitalization, study visits will be telephone or video encounters.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Aplastic Anemia</condition>
  <condition>Hematopoietic and Lymphoid Cell Neoplasm</condition>
  <condition>Malignant Solid Neoplasm</condition>
  <condition>Monoclonal B-Cell Lymphocytosis</condition>
  <condition>Monoclonal Gammopathy of Undetermined Significance</condition>
  <condition>Myelodysplastic Syndrome</condition>
  <condition>Symptomatic COVID-19 Infection Laboratory-Confirmed</condition>
  <arm_group>
    <arm_group_label>Arm A (ibrutinib)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive ibrutinib PO QD on days 1-7. Treatment repeats every 7 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients who remain hospitalized or are re-admitted after 2 cycles may receive an additional 2 cycles per physician's discretion.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B (usual care)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients receive usual care.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Best Practice</intervention_name>
    <description>Receive usual care</description>
    <arm_group_label>Arm B (usual care)</arm_group_label>
    <other_name>standard of care</other_name>
    <other_name>standard therapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ibrutinib</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm A (ibrutinib)</arm_group_label>
    <other_name>BTK Inhibitor PCI-32765</other_name>
    <other_name>CRA-032765</other_name>
    <other_name>Imbruvica</other_name>
    <other_name>PCI-32765</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  History or active diagnosis of cancer (solid or hematologic) or precursor of cancer&#xD;
             (monoclonal gammopathy of undetermined significance [MGUS]), monoclonal B&#xD;
             lymphocytosis (MBL), aplastic anemia or myelodysplastic syndrome) that is associated&#xD;
             with immune suppression&#xD;
&#xD;
          -  Hospitalization for confirmed polymerase chain reaction (PCR) positive COVID-19&#xD;
             infection&#xD;
&#xD;
          -  Patients with evidence of pulmonary involvement who meet any of the followings;&#xD;
             presence of infiltrates on chest X-ray or computed tomography (CT) scan or need for&#xD;
             supplemental oxygen &lt; 8 L nasal cannula or pulse oximetry &lt; 94% on room air&#xD;
&#xD;
          -  Creatinine clearance &gt;= 25 ml/min by Cockcroft-Gault equation&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 x upper limit of normal (ULN) unless bilirubin rise is due to&#xD;
             Gilbert's syndrome or of non-hepatic origin&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =&lt; 3 x ULN&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1000/mm^3 independent of growth factor support&#xD;
&#xD;
          -  Platelets &gt;= 50,000/mm^3&#xD;
&#xD;
          -  Ability to swallow capsules&#xD;
&#xD;
          -  Ability to provide informed consent indicating that they understand the purpose of and&#xD;
             procedures required for the study, including biomarkers, and are willing to&#xD;
             participate in the study&#xD;
&#xD;
          -  Women of childbearing potential and men who are sexually active must be practicing a&#xD;
             highly effective method of birth control during and after the study consistent with&#xD;
             local regulations regarding the use of birth control methods for subjects&#xD;
             participating in clinical trials. Men must agree to not donate sperm during and after&#xD;
             the study. For females, these restrictions apply for 1 month after the last dose of&#xD;
             study drug. For males, these restrictions apply for 3 months after the last dose of&#xD;
             study drug&#xD;
&#xD;
          -  Women of childbearing potential must have a negative serum (beta-human chorionic&#xD;
             gonadotropin [beta-hCG]) or urine pregnancy test at screening. Women who are pregnant&#xD;
             or breastfeeding are ineligible for this study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  New-onset malignancy requiring urgent initiation of systemic chemotherapy&#xD;
&#xD;
          -  Active uncontrolled systemic bacterial or fungal or other viral infection&#xD;
&#xD;
          -  Requires anticoagulation with warfarin or equivalent vitamin K antagonists (e.g.,&#xD;
             phenprocoumon)&#xD;
&#xD;
          -  Currently receiving BTK inhibitor therapy&#xD;
&#xD;
          -  Actively receiving anti-cancer therapy (other than hormonal therapies). All&#xD;
             anti-cancer therapy (except hormonal therapies) must be stopped at the time of&#xD;
             screening; can be resumed as soon as ibrutinib is discontinued. Significantly T cell&#xD;
             suppressive chemotherapy (defined as requiring PJP prophylaxis per standard&#xD;
             guidelines) is not allowed for 3 months prior to enrollment.&#xD;
&#xD;
          -  Clinically significant cardiovascular disease such as uncontrolled or symptomatic&#xD;
             arrhythmias, congestive heart failure, or myocardial infarction within 6 months of&#xD;
             screening, or any class 3 (moderate) or class 4 (severe) cardiac disease as defined by&#xD;
             the New York Heart Association Functional classification requirement for mechanical&#xD;
             ventilation at screening&#xD;
&#xD;
          -  Known bleeding disorders (e.g., Von Willebrand's disease, platelet storage pool&#xD;
             disorders, or hemophilia)&#xD;
&#xD;
          -  Stroke or intracranial hemorrhage within 6 months of screening&#xD;
&#xD;
          -  Major surgery or non-healing wound within 4 weeks of enrollment&#xD;
&#xD;
          -  Concomitant administration of prohibited medications&#xD;
&#xD;
          -  Known history of human immunodeficiency virus (HIV), or active hepatitis B or C&#xD;
             infection&#xD;
&#xD;
          -  Disease significantly affecting gastrointestinal function and/or inhibiting small&#xD;
             intestine absorption (malabsorption syndrome, resection of the small bowel, poorly&#xD;
             controlled inflammatory bowel disease, etc.)&#xD;
&#xD;
          -  Requires chronic treatment with strong CYP3A inhibitors&#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>Jennifer A Woyach, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ohio State University Comprehensive Cancer Center</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>
  <link>
    <url>http://cancer.osu.edu</url>
    <description>Jamesline</description>
  </link>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>June 17, 2020</study_first_submitted>
  <study_first_submitted_qc>June 18, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 19, 2020</study_first_posted>
  <last_update_submitted>March 31, 2023</last_update_submitted>
  <last_update_submitted_qc>March 31, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 5, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Ohio State University Comprehensive Cancer Center</investigator_affiliation>
    <investigator_full_name>Jennifer Woyach</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>COVID-19</mesh_term>
    <mesh_term>Laboratory Infection</mesh_term>
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Myelodysplastic Syndromes</mesh_term>
    <mesh_term>Anemia, Aplastic</mesh_term>
    <mesh_term>Paraproteinemias</mesh_term>
    <mesh_term>Monoclonal Gammopathy of Undetermined Significance</mesh_term>
    <mesh_term>Lymphocytosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>August 30, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/06/NCT04439006/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT04439006
org study id: OSU-20135
secondary id: NCI-2020-03341
nct id: NCT04439006
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase Ib/II trial studies the side effects and best dose of ibrutinib and how well it
      works in treating patients with COVID-19 requiring hospitalization. Ibrutinib may help
      improve COVID-19 symptoms by lessening the inflammatory response in the lungs, while
      preserving overall immune function. This may reduce the need to be on a ventilator to help
      with breathing.
PRIMARY OBJECTIVES:

      I. To determine the feasibility and tolerability of administering ibrutinib in COVID-19
      infected patients and determining the recommended phase 2 dose (RP2D). (Phase Ib) II. To
      determine whether ibrutinib administration (Arm A) in cancer patients can diminish the need
      for artificial ventilation (mechanical ventilation, bilevel positive airway pressure [BiPAP]
      or extracorporeal membrane oxygenation [ECMO]) or death due to COVID-19 as compared to
      untreated control population receiving standard therapy (antiviral, chloroquine,
      hydroxychloroquine, cytokine blocking peptides or small molecules) (Arm B). (Phase II)

      SECONDARY OBJECTIVES:

      I. To determine the time to defervescence (oral temperature < 100.5 degrees Fahrenheit [F]
      for a 48 hour time period) among patients treated with ibrutinib (Arm A) versus control
      population receiving standard (Arm B) therapy.

      II. To determine time to clinical resolution of need for supplemental oxygen (i.e.
      maintenance of oxygen saturation of 93% or greater on room air with ambulation).

      III. To determine rate of intensive care unit (ICU) admission and length of ICU admission for
      patients treated with ibrutinib (Arm A) versus control population receiving standard therapy
      (Arm B).

      IV. To determine rate of shock requiring vasopressor support for patients treated with
      ibrutinib (Arm A) versus control population receiving standard therapy (Arm B).

      V. To determine the rate of secondary infection (bacterial, fungal, viral) for patients
      treated with ibrutinib (Arm A) versus control population receiving standard therapy (Arm B).

      VI. To determine the time to hospital discharge for patients treated with ibrutinib (Arm A)
      versus control population receiving standard therapy (Arm B).

      VII. To determine time to hospital discharge and rate of death for patients who cross over to
      ibrutinib (Arm A) from standard therapy (Arm B).

      VIII. To determine grade 3 or higher toxicity observed in patients treated with ibrutinib
      (Arm A) versus control population receiving standard therapy (Arm B).

      IX. To determine time to mechanical ventilation, the number of days of mechanical ventilation
      per patient and total observed in patients treated with ibrutinib (Arm A) versus control
      population receiving standard therapy (Arm B).

      EXPLORATORY OBJECTIVES:

      I. To examine the impact of baseline clinical features (e.g. type of cancer, active therapy),
      duration of symptoms prior to admission and laboratory features (e.g. T cell count) on
      outcome for patients treated on this therapeutic study.

      II. To determine the proportion of patients with viral clearance at end of ibrutinib therapy,
      time of hospital discharge and follow up thereafter among patients treated with ibrutinib
      (Arm A) versus control (Arm B) treatment.

      III. To determine the time and proportion of patients who develop immunoglobulin (Ig)M and
      IgG levels toward SARS-coronavirus (CoV)-2 treated with ibrutinib (Arm A) versus control
      treatment (Arm B).

      IV. To examine immune cell subsets for absolute number, activation, exhaustion markers, and
      presence of maturation arrest (natural killer [NK] cells) at baseline and over time among
      patients treated with ibrutinib (Arm A) versus control (Arm B) treatment.

      V. To examine T-cell repertoire over time among patients treated with ibrutinib (Arm A)
      versus control (Arm B) treatment.

      VI. To determine the influence of epigenetic age, clonal hematopoiesis, and monoclonal B cell
      lymphocytosis (MBL) on treatment outcome.

      VII. To determine serial change in inflammatory markers as CRP, ferritin, D-dimer and
      cytokines including IL6, IL1B, and TNF-alpha serum levels over time among patients treated
      with ibrutinib (Arm A) versus control (Arm B) treatment.

      OUTLINE: This is a phase Ib, dose-escalation study followed by a phase II study.

      The first 12 patients will all receive ibrutinib. In the randomized part, patients are
      randomized to 1 of 2 arms.

      ARM A: Patients receive ibrutinib orally (PO) once daily (QD) on days 1-7. Treatment repeats
      every 7 days for 2 cycles in the absence of disease progression or unacceptable toxicity.
      Patients who remain hospitalized or are re-admitted after 2 cycles may receive an additional
      2 cycles per physician's discretion.

      ARM B: Patients receive usual care. Patients who meet the requirement of mechanical
      ventilation may cross-over to Arm A.

      After completion of study treatment, patients are followed up for up to 12 months.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of patients with diminished respiratory failure and death
time frame: During hospitalization for COVID-19 infection or within 30 days of registration
description: Associations between baseline characteristics and the primary endpoint will be evaluated with logistic regression, adjusting for arm. These analyses will be largely descriptive, as a result of a limited sample size.
measure: Death
time frame: During hospitalization for COVID-19 infection or within 30 days of registration
measure: Time from study initiation to 48 hours fever-free
time frame: Up to 14 days
description: Fever-free will be assessed by a temperature of < 100.5 degrees Fahrenheit orally. Will be estimated for each arm using the method of Kaplan-Meier. Medians estimates and/or estimates at specific time points will be provided with 95% confidence intervals.
measure: Duration of hospitalization
time frame: Up to 14 days
description: Will be estimated for each arm using the method of Kaplan-Meier. Medians estimates and/or estimates at specific time points will be provided with 95% confidence intervals.
measure: Time in intensive care unit (ICU)
time frame: Up to 14 days
measure: Time to ICU admission
time frame: Up to 14 days
measure: Number of days requiring supplemental oxygen
time frame: Up to 14 days
measure: Total days of mechanical ventilation
time frame: Up to 14 days
measure: Time to mechanical ventilation
time frame: Up to 14 days
measure: Shock and need for pressure support
time frame: Up to 14 days
measure: Incidence of any infection (viral, fungal, bacterial)
time frame: Up to 14 days
measure: Time to clinical resolution
time frame: Up to 14 days
measure: Incidence of grade 3 or higher adverse events
time frame: Up to 12 months
description: Adverse events will be summarized by grade, type, and attribution (regardless of attribution and treatment-related) for each arm.
measure: At the end of therapy (day 14)
time frame: Up to 14 days
description: The proportion of patients with viral clearance at the time of hospital discharge will be estimated with 95% confidence intervals for each arm.
measure: Time to viral clearance
time frame: Up to 12 months
description: Will be estimated for each arm using the method of Kaplan-Meier. Medians estimates and/or estimates at specific time points will be provided with 95% confidence intervals.
measure: Survival
time frame: Up to12 months
description: Patients will be followed for up to 12 months or until death or withdrawal of study consent for further follow-up. Following hospitalization, study visits will be telephone or video encounters.
arm group label: Arm A (ibrutinib)
arm group type: Experimental
description: Patients receive ibrutinib PO QD on days 1-7. Treatment repeats every 7 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients who remain hospitalized or are re-admitted after 2 cycles may receive an additional 2 cycles per physician's discretion.
arm group label: Arm B (usual care)
arm group type: Active Comparator
description: Patients receive usual care.
intervention type: Other
intervention name: Best Practice
description: Receive usual care
arm group label: Arm B (usual care)
other name: standard of care
other name: standard therapy
intervention type: Drug
intervention name: Ibrutinib
description: Given PO
arm group label: Arm A (ibrutinib)
other name: BTK Inhibitor PCI-32765
other name: CRA-032765
other name: Imbruvica
other name: PCI-32765
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jennifer A Woyach, MD
role: Principal Investigator
affiliation: Ohio State University Comprehensive Cancer Center
facility: 
country: United States
url: http://cancer.osu.edu
description: Jamesline
responsible party type: Sponsor-Investigator
investigator affiliation: Ohio State University Comprehensive Cancer Center
investigator full name: Jennifer Woyach
investigator title: Principal Investigator
mesh term: COVID-19
mesh term: Laboratory Infection
mesh term: Neoplasms
mesh term: Myelodysplastic Syndromes
mesh term: Anemia, Aplastic
mesh term: Paraproteinemias
mesh term: Monoclonal Gammopathy of Undetermined Significance
mesh term: Lymphocytosis
sharing ipd: No
provided document: 