<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/NCT03042585</url>
  </required_header>
  <id_info>
    <org_study_id>108993</org_study_id>
    <nct_id>NCT03042585</nct_id>
  </id_info>
  <brief_title>Autologous Transplant Using Dose-Escalated Total Body Irradiation &amp; Cyclophosphamide &amp; Palifermin for NHL</brief_title>
  <official_title>Phase I Study of Autologous Transplant Conditioned by Dose-Escalated Total Body Irradiation (TBI) and Standard Doses of Cyclophosphamide and Palifermin (Kepivance) for High Risk Non-Hodgkins Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Loyola University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Loyola University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Most participants with a relapsed or refractory non-Hodgkin's lymphoma that receive an&#xD;
      autologous transplant are likely to suffer a relapse because standard myeloablative&#xD;
      preparative regimens are unable to produce a cure. The majority of these participants do not&#xD;
      have a stem cell donor available, are too frail to undergo an allogeneic transplant, or&#xD;
      refuse an allograft. Historically these participants with high risk non-Hodgkin's lymphoma&#xD;
      have had a very poor outcome.&#xD;
&#xD;
      To take advantage of the low transplant related mortality associated with an autologous&#xD;
      transplantation, the investigators propose modifying the preparative regimen to make it more&#xD;
      effective without increasing toxicity. By increasing the dose of radiation while&#xD;
      administering the protective growth factor palifermin (Kepivance), the investigators hope to&#xD;
      decrease the risk of relapse without increasing transplant related mortality.&#xD;
&#xD;
      Three prospective randomized trials have studied different radiation schemes as a part of the&#xD;
      TBI and cytoxan preparative regimen prior to allogeneic transplantation for patients with AML&#xD;
      or CML. As a group these trials showed that higher doses of TBI in these older studies&#xD;
      decreased the risk of relapse at the expense of VOD, GVHD, and CMV. Three retrospective&#xD;
      studies have also postulated that higher dose radiation led to less risk of relapse.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a non-randomized, open-label phase I trial in participants with non-Hodgkin's&#xD;
      lymphoma. The preparative regimen will be as follows:&#xD;
&#xD;
      Day -10 (prior to transplant) Palifermin treatment to prevent mouth sores Day -9 Palifermin&#xD;
      treatment to prevent mouth sores Day -8 Palifermin treatment to prevent mouth sores Day -7&#xD;
      Total Body Irradiation twice a day Day -6 Total Body Irradiation twice a day Day -5 Total&#xD;
      Body Irradiation twice a day Day -4 Total Body Irradiation twice a day Day -3 Cytoxan&#xD;
      chemotherapy infusion Day -2 Cytoxan chemotherapy infusion Day -1 Day of rest Day 0 Stem cell&#xD;
      infusion (bone marrow transplant), Palifermin treatment to prevent mouth sores and G-CSF&#xD;
      given daily until stem cells take hold (engraftment) occurs.&#xD;
&#xD;
      Day +1 Palifermin treatment to prevent mouth sores Day +2 Palifermin treatment to prevent&#xD;
      mouth sores&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2006</start_date>
  <completion_date type="Actual">December 2018</completion_date>
  <primary_completion_date type="Actual">December 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Dose-Escalated Total Body Irradiation (TBI) of 4 levels. Palifermin (Kepivance) is being supplied by the sponsor and is FDA approved to decrease the incidence and duration of severe oral mucositis in participants with hematologic malignancies who receive high doses of chemotherapy and radiation therapy followed by stem cell rescue.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Determine the frequency and severity of adverse events by evaluating grade 3 and grade 4 adverse events.</measure>
    <time_frame>4 weeks</time_frame>
    <description>Any grade 3 or 4 dose limiting toxicities as described : • Heart failure with only minor response to medical therapy&#xD;
Hemorrhagic cystitis with frank blood requiring sclerosing agent or other surgical procedure&#xD;
Acute kidney failure requiring dialysis&#xD;
Interstitial pneumonitis requiring ventilatory support or FiO2 &gt; 50% x 24hrs&#xD;
Bilirubin &gt; 20 mg/dL&#xD;
Unexplained seizures or coma&#xD;
Severe mucositis requiring intubation for airway protection&#xD;
Ileus requiring nasogastric decompression.&#xD;
Death</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Blood work will be used to evaluate recovery of white blood cells, red blood cells and platelets.</measure>
    <time_frame>4 weeks</time_frame>
    <description>To evaluate labwork during treatment and for 28 days post treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pulmonary Function Test will be used to evaluate side effects of total body irradiation</measure>
    <time_frame>1 year</time_frame>
    <description>Pulmonary Function Test will be used to evaluate side effects of total body irradiation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CT scan or physical exam will be used to evaluate progression free survival.</measure>
    <time_frame>1 year</time_frame>
    <description>CT scan or physical exam will be used to evaluate progression free survival as deemed necessary.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mucositis measured by investigators.</measure>
    <time_frame>At the start of treatment and daily until mucositis resolves or 28 days post transplant whichever comes first.</time_frame>
    <description>Mucositis physical examination done by investigators by accessing the mouth using the WHO (World Health Organization) oral toxicity scale.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with Grade 4 through 5 Adverse Events that are related to study treatment, grading according to NCI CTCAE Version 3.</measure>
    <time_frame>28 days post treatment</time_frame>
    <description>Dose-limiting toxicities that are probably or definitely related to the treatment regimen.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mucositis measured by oral mucositis questionnaires</measure>
    <time_frame>At the start of treatment and daily until mucositis resolves or 28 days post transplant whichever comes first.</time_frame>
    <description>The participants will complete the oral mucositis daily questionnaires prior to the physical assessment. The questionnaire includes the participants self-reported mouth and throat soreness.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">17</enrollment>
  <condition>Relapsed Non Hodgkin Lymphoma</condition>
  <condition>Refractory Non-Hodgkin Lymphoma</condition>
  <arm_group>
    <arm_group_label>Dose Level 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The participants will receive Palifermin on Day -10, -9 and -8. Total Body Irradiation 1.64 Gy per Fraction for a total of 8 Fractions. The total amount would be 13.12 Gy. The participants will receive total body irradiation twice a day for four days (Day -7, -6, -5, and Day -4). Over the following two days, the participants will receive cyclophosphamide (Day -3 and -2). The participants will receive stem cell infusion on Day 0 and G-CSF given daily until engraftment occurs. Participants will receive Palifermin on Day 0, +1 and +2.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Level 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The participants will receive Palifermin on Day -10, -9 and -8. Total Body Irradiation 1.76 Gy per Fraction for a total of 8 Fractions. The total amount would be 14.08 Gy. The participants will receive total body irradiation twice a day for four days (Day -7, -6, -5, and Day -4). Over the following two days, the participants will receive cyclophosphamide (Day -3 and -2). The participants will receive stem cell infusion on Day 0 and G-CSF given daily until engraftment occurs. Participants will receive Palifermin on Day 0, +1 and +2.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Level 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The participants will receive Palifermin on Day -10, -9 and -8. Total Body Irradiation 1.88 Gy per Fraction for a total of 8 Fractions. The total amount would be 15.04 Gy. The participants will receive total body irradiation twice a day for four days (Day -7, -6, -5, and Day -4). Over the following two days, the participants will receive cyclophosphamide (Day -3 and -2). The participants will receive stem cell infusion on Day 0 and G-CSF given daily until engraftment occurs. Participants will receive Palifermin on Day 0, +1 and +2.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Level 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The participants will receive Palifermin on Day -10, -9 and -8. Total Body Irradiation 2.00 Gy per Fraction for a total of 8 Fractions. The total amount would be 16 Gy. The participants will receive total body irradiation twice a day for four days (Day -7, -6, -5, and Day -4). Over the following two days, the participants will receive cyclophosphamide (Day -3 and -2). The participants will receive stem cell infusion on Day 0 and G-CSF given daily until engraftment occurs. Participants will receive Palifermin on Day 0, +1 and +2.</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Total body irradiation</intervention_name>
    <description>When radiation is given in a way to cover the whole body, it is called total body irradiation.</description>
    <arm_group_label>Dose Level 1</arm_group_label>
    <arm_group_label>Dose Level 2</arm_group_label>
    <arm_group_label>Dose Level 3</arm_group_label>
    <arm_group_label>Dose Level 4</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 years of age or older&#xD;
&#xD;
          -  Participants scheduled to undergo autologous stem cell transplantation with relapsed&#xD;
             or refractory non-Hodgkin's Lymphoma with less than a partial remission to salvage&#xD;
             therapy.&#xD;
&#xD;
          -  Participants scheduled to undergo autologous stem cell transplantation with relapsed&#xD;
             or refractory non-Hodgkin's Lymphoma with any site of disease 2 cm or greater on&#xD;
             pre-transplant imaging.&#xD;
&#xD;
          -  Participants must have a performance status (PS) of 0-1.&#xD;
&#xD;
          -  Participants must have acceptable kidney function.&#xD;
&#xD;
          -  Acceptable pulmonary function test of the lungs.&#xD;
&#xD;
          -  Acceptable liver function tests.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants must not have cutaneous T-cell, mantle cell, or lymphoblastic lymphoma.&#xD;
&#xD;
          -  Participants must not have prior peripheral blood or marrow transplantation.&#xD;
&#xD;
          -  Participants must not have prior radiation.&#xD;
&#xD;
          -  Participants must not have significant history of uncontrolled cardiac disease; for&#xD;
             example, uncontrolled hypertension, unstable angina, recent myocardial infarction&#xD;
             (within prior 6 months), uncontrolled congestive heart failure, and cardiomyopathy&#xD;
             with decreased ejection fraction.&#xD;
&#xD;
          -  Participants must not have active bacterial, fungal, or viral infection.&#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>Patrick Stiff, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Loyola University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Patrick Stiff, MD</name>
      <address>
        <city>Maywood</city>
        <state>Illinois</state>
        <zip>60153</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>January 4, 2017</study_first_submitted>
  <study_first_submitted_qc>February 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 3, 2017</study_first_posted>
  <last_update_submitted>August 19, 2019</last_update_submitted>
  <last_update_submitted_qc>August 19, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 21, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Loyola University</investigator_affiliation>
    <investigator_full_name>Patrick Stiff</investigator_full_name>
    <investigator_title>MD and Director of Cardinal Bernardin Cancer Center</investigator_title>
  </responsible_party>
  <keyword>BMT</keyword>
  <keyword>NHL</keyword>
  <keyword>Non-Hodgkin Lymphoma</keyword>
  <keyword>Relapsed Non-Hodgkin Lymphoma</keyword>
  <keyword>Refractory Non-Hodgkin Lymphoma</keyword>
  <keyword>autologous stem cell transplantation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03042585
org study id: 108993
nct id: NCT03042585
lead sponsor: 
has dmc: Yes
Most participants with a relapsed or refractory non-Hodgkin's lymphoma that receive an
      autologous transplant are likely to suffer a relapse because standard myeloablative
      preparative regimens are unable to produce a cure. The majority of these participants do not
      have a stem cell donor available, are too frail to undergo an allogeneic transplant, or
      refuse an allograft. Historically these participants with high risk non-Hodgkin's lymphoma
      have had a very poor outcome.

      To take advantage of the low transplant related mortality associated with an autologous
      transplantation, the investigators propose modifying the preparative regimen to make it more
      effective without increasing toxicity. By increasing the dose of radiation while
      administering the protective growth factor palifermin (Kepivance), the investigators hope to
      decrease the risk of relapse without increasing transplant related mortality.

      Three prospective randomized trials have studied different radiation schemes as a part of the
      TBI and cytoxan preparative regimen prior to allogeneic transplantation for patients with AML
      or CML. As a group these trials showed that higher doses of TBI in these older studies
      decreased the risk of relapse at the expense of VOD, GVHD, and CMV. Three retrospective
      studies have also postulated that higher dose radiation led to less risk of relapse.
This is a non-randomized, open-label phase I trial in participants with non-Hodgkin's
      lymphoma. The preparative regimen will be as follows:

      Day -10 (prior to transplant) Palifermin treatment to prevent mouth sores Day -9 Palifermin
      treatment to prevent mouth sores Day -8 Palifermin treatment to prevent mouth sores Day -7
      Total Body Irradiation twice a day Day -6 Total Body Irradiation twice a day Day -5 Total
      Body Irradiation twice a day Day -4 Total Body Irradiation twice a day Day -3 Cytoxan
      chemotherapy infusion Day -2 Cytoxan chemotherapy infusion Day -1 Day of rest Day 0 Stem cell
      infusion (bone marrow transplant), Palifermin treatment to prevent mouth sores and G-CSF
      given daily until stem cells take hold (engraftment) occurs.

      Day +1 Palifermin treatment to prevent mouth sores Day +2 Palifermin treatment to prevent
      mouth sores
allocation: Non-Randomized
intervention model: Single Group Assignment
intervention model description: Dose-Escalated Total Body Irradiation (TBI) of 4 levels. Palifermin (Kepivance) is being supplied by the sponsor and is FDA approved to decrease the incidence and duration of severe oral mucositis in participants with hematologic malignancies who receive high doses of chemotherapy and radiation therapy followed by stem cell rescue.
primary purpose: Treatment
masking: None (Open Label)
measure: Determine the frequency and severity of adverse events by evaluating grade 3 and grade 4 adverse events.
time frame: 4 weeks
description: Any grade 3 or 4 dose limiting toxicities as described : • Heart failure with only minor response to medical therapy
Hemorrhagic cystitis with frank blood requiring sclerosing agent or other surgical procedure
Acute kidney failure requiring dialysis
Interstitial pneumonitis requiring ventilatory support or FiO2 > 50% x 24hrs
Bilirubin > 20 mg/dL
Unexplained seizures or coma
Severe mucositis requiring intubation for airway protection
Ileus requiring nasogastric decompression.
Death
measure: Blood work will be used to evaluate recovery of white blood cells, red blood cells and platelets.
time frame: 4 weeks
description: To evaluate labwork during treatment and for 28 days post treatment
measure: Pulmonary Function Test will be used to evaluate side effects of total body irradiation
time frame: 1 year
description: Pulmonary Function Test will be used to evaluate side effects of total body irradiation.
measure: CT scan or physical exam will be used to evaluate progression free survival.
time frame: 1 year
description: CT scan or physical exam will be used to evaluate progression free survival as deemed necessary.
measure: Mucositis measured by investigators.
time frame: At the start of treatment and daily until mucositis resolves or 28 days post transplant whichever comes first.
description: Mucositis physical examination done by investigators by accessing the mouth using the WHO (World Health Organization) oral toxicity scale.
measure: Number of participants with Grade 4 through 5 Adverse Events that are related to study treatment, grading according to NCI CTCAE Version 3.
time frame: 28 days post treatment
description: Dose-limiting toxicities that are probably or definitely related to the treatment regimen.
measure: Mucositis measured by oral mucositis questionnaires
time frame: At the start of treatment and daily until mucositis resolves or 28 days post transplant whichever comes first.
description: The participants will complete the oral mucositis daily questionnaires prior to the physical assessment. The questionnaire includes the participants self-reported mouth and throat soreness.
arm group label: Dose Level 1
arm group type: Experimental
description: The participants will receive Palifermin on Day -10, -9 and -8. Total Body Irradiation 1.64 Gy per Fraction for a total of 8 Fractions. The total amount would be 13.12 Gy. The participants will receive total body irradiation twice a day for four days (Day -7, -6, -5, and Day -4). Over the following two days, the participants will receive cyclophosphamide (Day -3 and -2). The participants will receive stem cell infusion on Day 0 and G-CSF given daily until engraftment occurs. Participants will receive Palifermin on Day 0, +1 and +2.
arm group label: Dose Level 2
arm group type: Experimental
description: The participants will receive Palifermin on Day -10, -9 and -8. Total Body Irradiation 1.76 Gy per Fraction for a total of 8 Fractions. The total amount would be 14.08 Gy. The participants will receive total body irradiation twice a day for four days (Day -7, -6, -5, and Day -4). Over the following two days, the participants will receive cyclophosphamide (Day -3 and -2). The participants will receive stem cell infusion on Day 0 and G-CSF given daily until engraftment occurs. Participants will receive Palifermin on Day 0, +1 and +2.
arm group label: Dose Level 3
arm group type: Experimental
description: The participants will receive Palifermin on Day -10, -9 and -8. Total Body Irradiation 1.88 Gy per Fraction for a total of 8 Fractions. The total amount would be 15.04 Gy. The participants will receive total body irradiation twice a day for four days (Day -7, -6, -5, and Day -4). Over the following two days, the participants will receive cyclophosphamide (Day -3 and -2). The participants will receive stem cell infusion on Day 0 and G-CSF given daily until engraftment occurs. Participants will receive Palifermin on Day 0, +1 and +2.
arm group label: Dose Level 4
arm group type: Experimental
description: The participants will receive Palifermin on Day -10, -9 and -8. Total Body Irradiation 2.00 Gy per Fraction for a total of 8 Fractions. The total amount would be 16 Gy. The participants will receive total body irradiation twice a day for four days (Day -7, -6, -5, and Day -4). Over the following two days, the participants will receive cyclophosphamide (Day -3 and -2). The participants will receive stem cell infusion on Day 0 and G-CSF given daily until engraftment occurs. Participants will receive Palifermin on Day 0, +1 and +2.
intervention type: Radiation
intervention name: Total body irradiation
description: When radiation is given in a way to cover the whole body, it is called total body irradiation.
arm group label: Dose Level 1
arm group label: Dose Level 2
arm group label: Dose Level 3
arm group label: Dose Level 4
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Patrick Stiff, MD
role: Principal Investigator
affiliation: Loyola University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Loyola University
investigator full name: Patrick Stiff
investigator title: MD and Director of Cardinal Bernardin Cancer Center
mesh term: Lymphoma
mesh term: Lymphoma, Non-Hodgkin
sharing ipd: No