<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/NCT01685606</url>
  </required_header>
  <id_info>
    <org_study_id>BrUOG 273</org_study_id>
    <nct_id>NCT01685606</nct_id>
  </id_info>
  <brief_title>Study of Infusion of Blood Cells (Lymphocytes) to Stimulate the Immune System to Fight Leukemia/Lymphoma</brief_title>
  <acronym>273</acronym>
  <official_title>BrUOG 273:Cellular Immunotherapy For Refractory Hematological Malignancies:A Brown University Oncology Research Group Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Brown University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Brown University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study of whether an infusion of blood cells called lymphocytes from a donor can stimulate&#xD;
      the immune system to fight your leukemia/lymphoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There have been important advances in the modulation of the immune system for the treatment&#xD;
      of hematologic malignancies and solid tumors.&#xD;
&#xD;
      This protocol will build upon these previous observations as follows:&#xD;
&#xD;
        -  Haploidentical peripheral blood pheresed cells will be used at 1-2x108 CD3 cells/kg.&#xD;
&#xD;
        -  Total body radiation will not be utilized.&#xD;
&#xD;
             -  This modification may more effectively activate the recipient's immune system to&#xD;
                attack their hematological malignancy by not damaging the recipient's immune cells&#xD;
                prior to cellular infusion. Safety should be improved since the risk of graft&#xD;
                versus host disease should be greatly reduced as the host's immune system will not&#xD;
                be conditioned.&#xD;
&#xD;
        -  Granulocyte-colony stimulating factor (G-CSF) priming will not be used.&#xD;
&#xD;
             -  In our first clinical trial, G-CSF priming was not used for matched transplants.&#xD;
                Our second trial did employ G-CSF priming in the haplo-identical setting. Previous&#xD;
                data has cited a role for G-CSF in stimulation of invariant Natural Killer(NK)&#xD;
                cells with enhanced GVL effects11. However, our most recent laboratory data with&#xD;
                unprimed PBMC has shown effective cell kill activity without the addition of G-CSF.&#xD;
                As G-CSF would be administered to healthy volunteers, the unclear benefit of the&#xD;
                addition of this cytokine is offset by the potential side effects such as headache,&#xD;
                fever, and bone pain. G-CSF mobilization serves to shift the response from a TH1 to&#xD;
                TH2 through the increased production of T regulatory cells. The end result would be&#xD;
                a decrease in immune stimulation. Since the goal of this study is to NOT have&#xD;
                engraftment, the manipulation of the donor cells to dampen the host versus tumor&#xD;
                stimulation is not needed nor desired. Furthermore, since this protocol is not a&#xD;
                stem cell transplant, stem cells do not need to be mobilized with G-CSF.&#xD;
&#xD;
      It is important to note that the proposed study is not a stem cell transplant study. In the&#xD;
      situation of stem cell transplants, the goal of the procedure is to have engraftment, or&#xD;
      sustainable donor chimerism in the marrow to provide hematopoietic reconstitution as well as&#xD;
      immunologic reconstitution. In this study, we are evaluating the use of donor lymphocytes&#xD;
      (not stem cells) to stimulate an immune response of the recipients' immune system.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Lack of accrual and low efficacy&#xD;
  </why_stopped>
  <start_date>March 2013</start_date>
  <completion_date type="Actual">June 2015</completion_date>
  <primary_completion_date type="Actual">June 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall Response Rate of Cellular Immune Therapy With HLA Haploidentical Peripheral Blood Pheresed Cells in Patients With Relapsed/Refractory Hematological Malignancies.</measure>
    <time_frame>8 weeks after infusion then 6 months after and every 4 months for approximately 2 years</time_frame>
    <description>Criteria for AML and ALL (adapted from Cheson et al.20)&#xD;
Complete remission (CR) is defined as the presence of all of the following&#xD;
Peripheral blood&#xD;
o No leukemic blasts present.&#xD;
No extramedullary findings of leukemia or disappearance of such (i.e. CNS or soft tissue involvement)&#xD;
Bone marrow&#xD;
Cellularity &gt;20% with baseline maturation.&#xD;
No Auer rods&#xD;
Less than 5% blast cells.&#xD;
Complete blood counts and bone marrow normalization criteria must be met within one week of each other. Hematopoeitic recovery is an ANC &gt; 1.0 x 109/L and platelet count &gt; 100x109/L. No specific hemoglobin or hematocrit level is specified but the patient must be transfusion free.&#xD;
Complete remission with incomplete recovery (CRi) is defined as the following:&#xD;
Meets criteria for CR except&#xD;
ANC &lt; 1.0 x 109/L or platelet count &lt; 100x109/L&#xD;
Partial remission (PR).&#xD;
• Must meet all criteria of a CR except that the bone marrow may contain 5-20% blasts.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To Evaluate the Rate of Dose Limiting Toxicities of HLA Haploidentical Peripheral Blood Pheresed Cellular Infusions.</measure>
    <time_frame>30 days and 16 weeks after infusion</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Mantle Cell Lymphoma</condition>
  <condition>Diffuse Large Cell Lymphoma</condition>
  <condition>Burkitts Lymphoma</condition>
  <condition>T Cell Lymphomas</condition>
  <condition>Acute Myeloid Leukemia/Acute Lymphoblastic Leukemia</condition>
  <arm_group>
    <arm_group_label>cellular immunotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A minimum of 1x108 CD3+ cells and maximum of 2x108 CD3+ cells/kg from a haploidentical donor will be infused, irrespective of the number of CD34+ cells.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>cellular immunotherapy</intervention_name>
    <description>A minimum of 1x108 CD3+ cells and maximum of 2x108 CD3+ cells/kg from a haploidentical donor irrespective of the number of CD34+ cells will be infused.</description>
    <arm_group_label>cellular immunotherapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologic confirmation of hematological malignancy consisting of the following&#xD;
             leukemias/lymphomas:&#xD;
&#xD;
          -  Mantle cell lymphoma with Ki-67&gt;30%&#xD;
&#xD;
          -  Diffuse Large Cell Lymphoma&#xD;
&#xD;
          -  Burkitts Lymphoma&#xD;
&#xD;
          -  Systemic T Cell Lymphomas&#xD;
&#xD;
          -  Acute Myeloid Leukemia&#xD;
&#xD;
          -  Acute Lymphoblastic Leukemia&#xD;
&#xD;
          -  Recurrence or progression of hematological malignancy after at least 1 prior standard&#xD;
             treatment with progression within 6 months from last treatment.&#xD;
&#xD;
          -  No curative treatment option is available.&#xD;
&#xD;
             -&gt; 4-weeks since prior chemotherapy or radiation to cellular therapy infusion.&#xD;
             (Hydroxyurea may be utilized up to 48 hours prior to initiation of treatment on this&#xD;
             protocol).&#xD;
&#xD;
          -  Age equal to or greater than 18 years.&#xD;
&#xD;
          -  Patients with a history of invasive second malignancy unless disease free for &gt; 5&#xD;
             years.&#xD;
&#xD;
          -  Patients must have an expected life expectancy of at least 2 months at the time of&#xD;
             initiation of treatment.&#xD;
&#xD;
          -  No active systemic infection.&#xD;
&#xD;
          -  Patients who have relapsed after standard autologous stem cell infusion are eligible&#xD;
             as long as they meet all inclusion criteria and no exclusion criteria. These patients&#xD;
             must be out more than 6 months from cell infusion to be eligible for enrollment.&#xD;
&#xD;
          -  DLCO &gt; 40% with no symptomatic pulmonary disease.&#xD;
&#xD;
          -  LVEF &gt; 40% by MUGA or echocardiogram.&#xD;
&#xD;
          -  Creatinine &lt; 2.0 mg/dl. Total bilirubin less than 1.5x the upper limit of normal&#xD;
             (ULN), AST &lt; 3x ULN.&#xD;
&#xD;
          -  Non-pregnant and willing to use appropriate birth control during the duration of the&#xD;
             study period.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Evidence of HIV infection.&#xD;
&#xD;
          -  Any uncontrolled severe, concurrent illness which in the opinion of the treating&#xD;
             physician would make this protocol treatment unreasonably hazardous for the patient.&#xD;
&#xD;
          -  Oxygen dependent obstructive pulmonary disease.&#xD;
&#xD;
          -  Failure to demonstrate adequate compliance with medical therapy and follow-up.&#xD;
&#xD;
          -  Significant medical or psychiatric illness that would impair the ability to&#xD;
             participate in protocol therapy.&#xD;
&#xD;
          -  For women of reproductive potential, refusal to use effective form of contraception.&#xD;
&#xD;
          -  Previous allogeneic stem cell transplant&#xD;
&#xD;
          -  Patients who have had previous purine analog (fludarabine, pentostatin, 2-CDA)&#xD;
             -Patients with chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL),&#xD;
             multiple myeloma, and indolent lymphoma (follicular lymphoma, marginal zone lymphoma)&#xD;
&#xD;
          -  Patients with HLA antibodies to donor HLA type.&#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>Peter Quesenberry, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Brown University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Rhode Island Hospital</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Miriam Hospital</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>September 12, 2012</study_first_submitted>
  <study_first_submitted_qc>September 12, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 14, 2012</study_first_posted>
  <results_first_submitted>June 4, 2015</results_first_submitted>
  <results_first_submitted_qc>June 4, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">June 26, 2015</results_first_posted>
  <last_update_submitted>February 23, 2022</last_update_submitted>
  <last_update_submitted_qc>February 23, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 4, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Leukemia</keyword>
  <keyword>Lymphoma</keyword>
  <keyword>Mantle cell</keyword>
  <keyword>DLBCL</keyword>
  <keyword>DLBC</keyword>
  <keyword>Diffuse large B cell</keyword>
  <keyword>T cell</keyword>
  <keyword>AML</keyword>
  <keyword>ALL</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Burkitt Lymphoma</mesh_term>
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Lymphoma, Mantle-Cell</mesh_term>
    <mesh_term>Lymphoma, Large B-Cell, Diffuse</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Immunomodulating Agents</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Cellular Immunotherapy</title>
          <description>A minimum of 1x108 CD3+ cells and maximum of 2x108 CD3+ cells/kg from a haploidentical donor will be infused, irrespective of the number of CD34+ cells.&#xD;
cellular immunotherapy: A minimum of 1x108 CD3+ cells and maximum of 2x108 CD3+ cells/kg from a haploidentical donor irrespective of the number of CD34+ cells will be infused.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Cellular Immunotherapy</title>
          <description>A minimum of 1x108 CD3+ cells and maximum of 2x108 CD3+ cells/kg from a haploidentical donor will be infused, irrespective of the number of CD34+ cells.&#xD;
cellular immunotherapy: A minimum of 1x108 CD3+ cells and maximum of 2x108 CD3+ cells/kg from a haploidentical donor irrespective of the number of CD34+ cells will be infused.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="5"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="66.2" lower_limit="52" upper_limit="77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Overall Response Rate of Cellular Immune Therapy With HLA Haploidentical Peripheral Blood Pheresed Cells in Patients With Relapsed/Refractory Hematological Malignancies.</title>
        <description>Criteria for AML and ALL (adapted from Cheson et al.20)&#xD;
Complete remission (CR) is defined as the presence of all of the following&#xD;
Peripheral blood&#xD;
o No leukemic blasts present.&#xD;
No extramedullary findings of leukemia or disappearance of such (i.e. CNS or soft tissue involvement)&#xD;
Bone marrow&#xD;
Cellularity &gt;20% with baseline maturation.&#xD;
No Auer rods&#xD;
Less than 5% blast cells.&#xD;
Complete blood counts and bone marrow normalization criteria must be met within one week of each other. Hematopoeitic recovery is an ANC &gt; 1.0 x 109/L and platelet count &gt; 100x109/L. No specific hemoglobin or hematocrit level is specified but the patient must be transfusion free.&#xD;
Complete remission with incomplete recovery (CRi) is defined as the following:&#xD;
Meets criteria for CR except&#xD;
ANC &lt; 1.0 x 109/L or platelet count &lt; 100x109/L&#xD;
Partial remission (PR).&#xD;
• Must meet all criteria of a CR except that the bone marrow may contain 5-20% blasts.</description>
        <time_frame>8 weeks after infusion then 6 months after and every 4 months for approximately 2 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cellular Immunotherapy</title>
            <description>A minimum of 1x108 CD3+ cells and maximum of 2x108 CD3+ cells/kg from a haploidentical donor will be infused, irrespective of the number of CD34+ cells.&#xD;
cellular immunotherapy: A minimum of 1x108 CD3+ cells and maximum of 2x108 CD3+ cells/kg from a haploidentical donor irrespective of the number of CD34+ cells will be infused.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response Rate of Cellular Immune Therapy With HLA Haploidentical Peripheral Blood Pheresed Cells in Patients With Relapsed/Refractory Hematological Malignancies.</title>
          <description>Criteria for AML and ALL (adapted from Cheson et al.20)&#xD;
Complete remission (CR) is defined as the presence of all of the following&#xD;
Peripheral blood&#xD;
o No leukemic blasts present.&#xD;
No extramedullary findings of leukemia or disappearance of such (i.e. CNS or soft tissue involvement)&#xD;
Bone marrow&#xD;
Cellularity &gt;20% with baseline maturation.&#xD;
No Auer rods&#xD;
Less than 5% blast cells.&#xD;
Complete blood counts and bone marrow normalization criteria must be met within one week of each other. Hematopoeitic recovery is an ANC &gt; 1.0 x 109/L and platelet count &gt; 100x109/L. No specific hemoglobin or hematocrit level is specified but the patient must be transfusion free.&#xD;
Complete remission with incomplete recovery (CRi) is defined as the following:&#xD;
Meets criteria for CR except&#xD;
ANC &lt; 1.0 x 109/L or platelet count &lt; 100x109/L&#xD;
Partial remission (PR).&#xD;
• Must meet all criteria of a CR except that the bone marrow may contain 5-20% blasts.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>To Evaluate the Rate of Dose Limiting Toxicities of HLA Haploidentical Peripheral Blood Pheresed Cellular Infusions.</title>
        <time_frame>30 days and 16 weeks after infusion</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cellular Immunotherapy</title>
            <description>A minimum of 1x108 CD3+ cells and maximum of 2x108 CD3+ cells/kg from a haploidentical donor will be infused, irrespective of the number of CD34+ cells.&#xD;
cellular immunotherapy: A minimum of 1x108 CD3+ cells and maximum of 2x108 CD3+ cells/kg from a haploidentical donor irrespective of the number of CD34+ cells will be infused.</description>
          </group>
        </group_list>
        <measure>
          <title>To Evaluate the Rate of Dose Limiting Toxicities of HLA Haploidentical Peripheral Blood Pheresed Cellular Infusions.</title>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Cellular Immunotherapy</title>
          <description>A minimum of 1x108 CD3+ cells and maximum of 2x108 CD3+ cells/kg from a haploidentical donor will be infused, irrespective of the number of CD34+ cells.&#xD;
cellular immunotherapy: A minimum of 1x108 CD3+ cells and maximum of 2x108 CD3+ cells/kg from a haploidentical donor irrespective of the number of CD34+ cells will be infused.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Albumin</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>ALT</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>anemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>AST</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>bone pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>ca</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>CRS (pt 3 included n, ha, r)</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>diarrhea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>dizziness</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Febrile Neutropenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>fever</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>pain-neck</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>PLT</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>creatinine</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>infection: wound</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>GI bleed</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>alk phos</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>anemia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>anxiety</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>arthralgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>bleeding scrotum</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>bone pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>ca</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>diarrhea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>cough</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>edema</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>epistaxis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>erythema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>eye stye Not graded pt 3</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>fever</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>K</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Leukocytosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Lymph</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>minor bleeding superficila leg lesions &quot;minor&quot; NG pt #3</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>oral thrush</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Phos</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>PLT</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>post nasal</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>segs/neuts</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>sinus pain Not graded pt 3</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>sinus tach</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>WBC</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>cellulitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>fatigue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>LE pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Peter Quesenberry</name_or_title>
      <organization>Brown University Oncology Research Group (BrUOG)</organization>
      <phone>4018633000</phone>
      <email>kayla_rosati@brown.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01685606
org study id: BrUOG 273
nct id: NCT01685606
lead sponsor: 
has dmc: Yes
The study of whether an infusion of blood cells called lymphocytes from a donor can stimulate
      the immune system to fight your leukemia/lymphoma.
There have been important advances in the modulation of the immune system for the treatment
      of hematologic malignancies and solid tumors.

      This protocol will build upon these previous observations as follows:

        -  Haploidentical peripheral blood pheresed cells will be used at 1-2x108 CD3 cells/kg.

        -  Total body radiation will not be utilized.

             -  This modification may more effectively activate the recipient's immune system to
                attack their hematological malignancy by not damaging the recipient's immune cells
                prior to cellular infusion. Safety should be improved since the risk of graft
                versus host disease should be greatly reduced as the host's immune system will not
                be conditioned.

        -  Granulocyte-colony stimulating factor (G-CSF) priming will not be used.

             -  In our first clinical trial, G-CSF priming was not used for matched transplants.
                Our second trial did employ G-CSF priming in the haplo-identical setting. Previous
                data has cited a role for G-CSF in stimulation of invariant Natural Killer(NK)
                cells with enhanced GVL effects11. However, our most recent laboratory data with
                unprimed PBMC has shown effective cell kill activity without the addition of G-CSF.
                As G-CSF would be administered to healthy volunteers, the unclear benefit of the
                addition of this cytokine is offset by the potential side effects such as headache,
                fever, and bone pain. G-CSF mobilization serves to shift the response from a TH1 to
                TH2 through the increased production of T regulatory cells. The end result would be
                a decrease in immune stimulation. Since the goal of this study is to NOT have
                engraftment, the manipulation of the donor cells to dampen the host versus tumor
                stimulation is not needed nor desired. Furthermore, since this protocol is not a
                stem cell transplant, stem cells do not need to be mobilized with G-CSF.

      It is important to note that the proposed study is not a stem cell transplant study. In the
      situation of stem cell transplants, the goal of the procedure is to have engraftment, or
      sustainable donor chimerism in the marrow to provide hematopoietic reconstitution as well as
      immunologic reconstitution. In this study, we are evaluating the use of donor lymphocytes
      (not stem cells) to stimulate an immune response of the recipients' immune system.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Response Rate of Cellular Immune Therapy With HLA Haploidentical Peripheral Blood Pheresed Cells in Patients With Relapsed/Refractory Hematological Malignancies.
time frame: 8 weeks after infusion then 6 months after and every 4 months for approximately 2 years
description: Criteria for AML and ALL (adapted from Cheson et al.20)
Complete remission (CR) is defined as the presence of all of the following
Peripheral blood
o No leukemic blasts present.
No extramedullary findings of leukemia or disappearance of such (i.e. CNS or soft tissue involvement)
Bone marrow
Cellularity >20% with baseline maturation.
No Auer rods
Less than 5% blast cells.
Complete blood counts and bone marrow normalization criteria must be met within one week of each other. Hematopoeitic recovery is an ANC > 1.0 x 109/L and platelet count > 100x109/L. No specific hemoglobin or hematocrit level is specified but the patient must be transfusion free.
Complete remission with incomplete recovery (CRi) is defined as the following:
Meets criteria for CR except
ANC < 1.0 x 109/L or platelet count < 100x109/L
Partial remission (PR).
• Must meet all criteria of a CR except that the bone marrow may contain 5-20% blasts.
measure: To Evaluate the Rate of Dose Limiting Toxicities of HLA Haploidentical Peripheral Blood Pheresed Cellular Infusions.
time frame: 30 days and 16 weeks after infusion
arm group label: cellular immunotherapy
arm group type: Experimental
description: A minimum of 1x108 CD3+ cells and maximum of 2x108 CD3+ cells/kg from a haploidentical donor will be infused, irrespective of the number of CD34+ cells.
intervention type: Biological
intervention name: cellular immunotherapy
description: A minimum of 1x108 CD3+ cells and maximum of 2x108 CD3+ cells/kg from a haploidentical donor irrespective of the number of CD34+ cells will be infused.
arm group label: cellular immunotherapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Peter Quesenberry, MD
role: Principal Investigator
affiliation: Brown University
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Burkitt Lymphoma
mesh term: Lymphoma
mesh term: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Lymphoma, Mantle-Cell
mesh term: Lymphoma, Large B-Cell, Diffuse
mesh term: Immunomodulating Agents
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 