<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/NCT03277729</url>
  </required_header>
  <id_info>
    <org_study_id>9738</org_study_id>
    <secondary_id>NCI-2017-01595</secondary_id>
    <secondary_id>9738</secondary_id>
    <secondary_id>RG9217017</secondary_id>
    <nct_id>NCT03277729</nct_id>
  </id_info>
  <brief_title>A Phase I/II Study to Evaluate the Safety of Cellular Immunotherapy Using Autologous T Cells Engineered to Express a CD20-Specific Chimeric Antigen Receptor for Patients With Relapsed or Refractory B Cell Non-Hodgkin Lymphomas</brief_title>
  <official_title>A Phase I/II Study to Evaluate the Safety of Cellular Immunotherapy Using Autologous T Cells Engineered to Express a CD20-Specific Chimeric Antigen Receptor for Patients With Relapsed or Refractory B Cell Non-Hodgkin Lymphomas</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fred Hutchinson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Mustang Bio</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Fred Hutchinson 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>
      The purpose of this research is to find the best dose of genetically modified T-cells, to&#xD;
      study the safety of this treatment, and to see how well it works in treating patients with B&#xD;
      cell non-Hodgkin lymphoma that has come back (relapsed) or did not respond to previous&#xD;
      treatment (refractory).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      OUTLINE:&#xD;
&#xD;
      This is a phase I/II dose-escalation study of CD20-specific CAR T cell therapy.&#xD;
&#xD;
      Patients undergo leukapheresis and may receive treatment after if needed for disease control.&#xD;
      Patients then receive cyclophosphamide intravenously (IV). Patients may also receive&#xD;
      fludarabine IV. After 36-96 hours, patients receive CD20-specific CAR T cell infusion IV over&#xD;
      20-30 minutes.&#xD;
&#xD;
      Patients will be actively participating in the study for approximately 15 months. The total&#xD;
      time includes the time for the T cells to be made, the T cell infusion, and for approximately&#xD;
      12 months after the T cell infusion is given. After completion of study treatment, patients&#xD;
      are followed up for a minimum of 15 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 5, 2017</start_date>
  <completion_date type="Anticipated">November 16, 2037</completion_date>
  <primary_completion_date type="Anticipated">November 16, 2024</primary_completion_date>
  <phase>Phase 1/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>Dose-limiting toxicity</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Will be graded by Common Terminology Criteria for Adverse Events version 4.0.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Complete remission</measure>
    <time_frame>Up to 15 years</time_frame>
    <description>Will be assessed based on the Lugano criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>Duration from study enrollment to progression or death due to any cause (whichever comes first), assessed up to 15 years</time_frame>
    <description>A Cox proportional hazards model will be used to evaluate PFS.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>Duration from study enrollment to death due to any cause, assessed up to 15 years</time_frame>
    <description>A Cox proportional hazards model will be used to evaluate OS.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events</measure>
    <time_frame>Up to 15 years</time_frame>
    <description>Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Recurrent B-Cell Non-Hodgkin Lymphoma</condition>
  <condition>Recurrent Chronic Lymphocytic Leukemia</condition>
  <condition>Recurrent Diffuse Large B-Cell Lymphoma</condition>
  <condition>Recurrent Follicular Lymphoma</condition>
  <condition>Recurrent Lymphoplasmacytic Lymphoma</condition>
  <condition>Recurrent Mantle Cell Lymphoma</condition>
  <condition>Recurrent Marginal Zone Lymphoma</condition>
  <condition>Refractory B-Cell Non-Hodgkin Lymphoma</condition>
  <condition>Refractory Diffuse Large B-Cell Lymphoma</condition>
  <condition>Refractory Follicular Lymphoma</condition>
  <condition>Refractory Lymphoplasmacytic Lymphoma</condition>
  <condition>Refractory Mantle Cell Lymphoma</condition>
  <condition>Refractory Transformed Non-Hodgkin Lymphoma</condition>
  <condition>Recurrent Transformed B-Cell Non-Hodgkin Lymphoma</condition>
  <condition>Recurrent Transformed Chronic Lymphocytic Leukemia</condition>
  <condition>Refractory Marginal Zone Lymphoma</condition>
  <condition>Refractory Transformed B-Cell Non-Hodgkin Lymphoma</condition>
  <condition>Refractory Transformed Chronic Lymphocytic Leukemia</condition>
  <condition>Recurrent Small Lymphocytic Lymphoma</condition>
  <condition>Refractory Chronic Lymphocytic Leukemia</condition>
  <condition>Refractory Small Lymphocytic Lymphoma</condition>
  <condition>Recurrent Central Nervous System Lymphoma</condition>
  <condition>Refractory Central Nervous System Lymphoma</condition>
  <arm_group>
    <arm_group_label>Treatment (CD20-specific CAR T cell, chemotherapy)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients undergo leukapheresis and may receive treatment after if needed for disease control. Patients then receive cyclophosphamide IV. Patients may also receive fludarabine IV. After 36-96 hours, patients receive CD20-specific CAR T cell infusion IV over 20-30 minutes.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Chimeric Antigen Receptor T-Cell Therapy</intervention_name>
    <description>Given CD20 CAR T cell IV</description>
    <arm_group_label>Treatment (CD20-specific CAR T cell, chemotherapy)</arm_group_label>
    <other_name>CAR T-cell therapy</other_name>
    <other_name>CAR T Infusion</other_name>
    <other_name>CAR T Therapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (CD20-specific CAR T cell, chemotherapy)</arm_group_label>
    <other_name>(-)-Cyclophosphamide</other_name>
    <other_name>2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate</other_name>
    <other_name>Carloxan</other_name>
    <other_name>Ciclofosfamida</other_name>
    <other_name>Ciclofosfamide</other_name>
    <other_name>Cicloxal</other_name>
    <other_name>Clafen</other_name>
    <other_name>Claphene</other_name>
    <other_name>CP monohydrate</other_name>
    <other_name>CTX</other_name>
    <other_name>CYCLO-cell</other_name>
    <other_name>Cycloblastin</other_name>
    <other_name>Cycloblastine</other_name>
    <other_name>Cyclophospham</other_name>
    <other_name>Cyclophosphamid monohydrate</other_name>
    <other_name>Cyclophosphamidum</other_name>
    <other_name>Cyclophosphan</other_name>
    <other_name>Cyclophosphane</other_name>
    <other_name>Cyclophosphanum</other_name>
    <other_name>Cyclostin</other_name>
    <other_name>Cyclostine</other_name>
    <other_name>Cytophosphan</other_name>
    <other_name>Cytophosphane</other_name>
    <other_name>Cytoxan</other_name>
    <other_name>Fosfaseron</other_name>
    <other_name>Genoxal</other_name>
    <other_name>Genuxal</other_name>
    <other_name>Ledoxina</other_name>
    <other_name>Mitoxan</other_name>
    <other_name>Neosar</other_name>
    <other_name>Revimmune</other_name>
    <other_name>Syklofosfamid</other_name>
    <other_name>WR- 138719</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (CD20-specific CAR T cell, chemotherapy)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Leukapheresis</intervention_name>
    <description>Undergo leukapheresis</description>
    <arm_group_label>Treatment (CD20-specific CAR T cell, chemotherapy)</arm_group_label>
    <other_name>Leukocytopheresis</other_name>
    <other_name>Therapeutic Leukopheresis</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fludarabine Phosphate</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (CD20-specific CAR T cell, chemotherapy)</arm_group_label>
    <other_name>2-F-ara-AMP</other_name>
    <other_name>Beneflur</other_name>
    <other_name>Fludara</other_name>
    <other_name>Fludarabine-5''-Monophosphate</other_name>
    <other_name>SH T 586</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have B-cell non-Hodgkin lymphoma or chronic lymphocytic leukemia/small&#xD;
             lymphocytic lymphoma. Eligible lymphoma subtypes include (but not limited to): mantle&#xD;
             cell, follicular, lymphoplasmacytic, marginal zone, transformed indolent B cell&#xD;
             lymphoma (including transformed chronic lymphoid leukemia [CLL]), or diffuse large B&#xD;
             cell lymphoma that has relapsed after a response to at least one prior therapy regimen&#xD;
             or is refractory to prior therapy; patients with mantle cell lymphoma must have&#xD;
             previously been treated with a Bruton tyrosine kinase (BTK) inhibitor and have either&#xD;
             had disease progression, intolerance, or exposure to the drug for at least 3 months;&#xD;
             patients with CLL/SLL are eligible if they had disease progression or intolerance to&#xD;
             BTKis and/or a BCL-2 inhibitors; they are also required to have been treated with the&#xD;
             other agent for at least 3 months (i.e. patients with progression/intolerance to BTKi&#xD;
             need to be treated with a BCL-2 inhibitor for at least 3 months, and patients with&#xD;
             progression/intolerance to BCL-2 inhibitor need at least 3 months of exposure to a&#xD;
             BTKi); patients with de novo diffuse large B-cell lymphoma (DLBCL) must meet one of&#xD;
             the following criteria:&#xD;
&#xD;
               -  Biopsy-proven refractory disease after a frontline regimen containing both an&#xD;
                  anthracycline and rituximab or other anti-CD20 antibody (i.e. &quot;primary&#xD;
                  refractory&quot;), where any disease recurring within 6 months of completion of the&#xD;
                  regimen is considered refractory&#xD;
&#xD;
               -  Relapsed or refractory disease after at least one of the following:&#xD;
&#xD;
                    -  At least 2 lines of therapy (including at least one with an anthracycline&#xD;
                       and anti-CD20 antibody)&#xD;
&#xD;
                    -  Autologous stem cell transplant&#xD;
&#xD;
                    -  Allogeneic stem cell transplant&#xD;
&#xD;
          -  Patients with large cell lymphoma transformed from indolent lymphomas are eligible if&#xD;
             previously treated with anthracycline containing regimen for either the indolent or&#xD;
             large cell histology&#xD;
&#xD;
          -  Patients with central nervous system (CNS) lymphoma need to meet one of the following&#xD;
             criteria:&#xD;
&#xD;
               -  Primary CNS lymphoma:&#xD;
&#xD;
                    -  Progressive disease after 3 cycles or an inadequate response after at least&#xD;
                       4 cycles of a high-dose methotrexate (MTX) containing regimen in the opinion&#xD;
                       of the treating physician, OR&#xD;
&#xD;
                    -  Not eligible for MTX therapy due to commodities or tolerance issues per&#xD;
                       treating physician OR&#xD;
&#xD;
                    -  Recurrent disease after an initial response to MTX-based treatment&#xD;
&#xD;
               -  Secondary CNS lymphoma:&#xD;
&#xD;
                    -  An inadequate rtesponse to at least 2 cycles of a MTX containing regimen, OR&#xD;
&#xD;
                    -  Recurrent disease after an initial response to MTX-based treatment&#xD;
&#xD;
          -  Patients must be 18 years of age or older, of any gender, race or ethnicity&#xD;
&#xD;
          -  Patients must be capable of understanding and providing a written informed consent&#xD;
&#xD;
          -  Negative serum pregnancy test within 2 weeks before enrollment for women of&#xD;
             childbearing potential, defined as those who have not been surgically sterilized or&#xD;
             who have not been free of menses for at least 1 year&#xD;
&#xD;
          -  Fertile male and female patients must be willing to use an effective contraceptive&#xD;
             method before, during, and for at least 4 months after the CAR T cell infusion&#xD;
&#xD;
          -  Patients must have a Karnofsky performance status of &gt;= 60%&#xD;
&#xD;
          -  Confirmation of diagnosis by internal pathology review of initial or subsequent biopsy&#xD;
             or other pathologic material at Fred Hutchinson Cancer Research Center (FHCRC)/Seattle&#xD;
             Cancer Care Alliance (SCCA)/University of Washington (UW)/Harborview Medical Center&#xD;
             (HMC)&#xD;
&#xD;
          -  Evidence of CD20 expression by immunohistochemistry or flow cytometry on the tumor&#xD;
             specimen obtained with the biopsy performed with screening; if the CD20 expression on&#xD;
             the screening tumor biopsy is unclear or could not be assessed due to technical&#xD;
             reasons, CD20 expression on a concomitant tumor specimen (such as marrow biopsy or&#xD;
             circulating tumor cells) may be used to satisfy this requirement. For CLL and&#xD;
             lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (WM) patients, the screening&#xD;
             tumor biopsy can we waived for clinical reasons after discussion with the study&#xD;
             principal investigator (PI). For patients with CNS lymphoma, a screening tumor biopsy&#xD;
             is not required and evidence of CD20 expression can be documented from the original or&#xD;
             prior biopsies&#xD;
&#xD;
          -  Serum creatinine =&lt; 2.5&#xD;
&#xD;
          -  Total bilirubin =&lt; 3.0 mg/dL&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =&lt; 5 x the upper&#xD;
             limit of normal&#xD;
&#xD;
          -  Adequate pulmonary function, defined as =&lt; grade 1 dyspnea and saturated oxygen (SaO2)&#xD;
             &gt;= 92% on room air; if pulmonary function test (PFT)s are performed based on the&#xD;
             clinical judgment of the treating physician, patients with forced expiratory volume in&#xD;
             1 second (FEV1) &gt;= 50% of predicted and carbon monoxide diffusing capability (DLCO)&#xD;
             (corrected) of &gt;= 40% of predicted will be eligible&#xD;
&#xD;
          -  Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) of &gt;=&#xD;
             50% as assessed by echocardiogram or multigated acquisition (MUGA) scan, or LVEF of&#xD;
             45-49% and clearance by a cardiologist&#xD;
&#xD;
          -  Measurable disease that can be accurately measured in at least one dimension as &gt;= 1.5&#xD;
             cm with computed tomography (CT), ultrasound, or magnetic resonance imaging (MRI)&#xD;
             techniques. Extranodal disease that is measurable by fludeoxyglucose F-18&#xD;
             (FDG)-positron emission tomography (PET) imaging only will also be allowed. Note that&#xD;
             if an excisional biopsy was performed that removed the sole site of measurable&#xD;
             disease, the patient will not be eligible for leukapheresis and generation of CAR T&#xD;
             cell product&#xD;
&#xD;
          -  For patients with CNS lymphoma, a lesion &gt;= 1cm on brain or spine MRI is required&#xD;
&#xD;
          -  Patients with waldenstrom macroglobulinemia (WM) without radiologic evidence of&#xD;
             disease are eligible if they have measurable disease, as defined by serum monoclonal&#xD;
             M-spike of &gt;= 0.5 g/dL&#xD;
&#xD;
          -  ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: Absence of uncontrolled active infection&#xD;
             (bacterial, fungal, viral, mycobacterial) not responding to treatment with&#xD;
             antibiotics, antiviral agents, or antifungal agents&#xD;
&#xD;
          -  ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: Absence of active autoimmune disease&#xD;
             requiring ongoing systemic immunosuppressive therapy&#xD;
&#xD;
          -  ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: Negative serum pregnancy test within 2&#xD;
             weeks before lymphodepletion chemotherapy for women of childbearing potential, defined&#xD;
             as those who have not been surgically sterilized or who have not been free of menses&#xD;
             for at least 1 year&#xD;
&#xD;
          -  ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: No treatment with any investigational&#xD;
             agent on a different clinical trial between enrollment and lymphodepleting&#xD;
             chemotherapy&#xD;
&#xD;
          -  ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: Serum creatinine =&lt; 2.5&#xD;
&#xD;
          -  ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: Total bilirubin =&lt; 3.0 mg/dL&#xD;
&#xD;
          -  ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: AST and ALT =&lt; 5 x the upper limit of&#xD;
             normal&#xD;
&#xD;
          -  ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: Adequate pulmonary function, defined as&#xD;
             =&lt; grade 1 dyspnea and SaO2 &gt;= 92% on room air; if PFTs are performed based on the&#xD;
             clinical judgment of the treating physician, patients with FEV1 &gt;= 50% of predicted&#xD;
             and DLCO (corrected) of &gt;= 40% of predicted will be eligible&#xD;
&#xD;
          -  ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: Adequate cardiac function, defined as&#xD;
             left ventricular ejection fraction (LVEF) of &gt;= 50% as assessed by echocardiogram or&#xD;
             MUGA scan, or LVEF of 45-49% and clearance by a cardiologist; if subject receives&#xD;
             cardiotoxic chemotherapy after enrollment, repeat echocardiogram or MUGA is required&#xD;
             to reestablish eligible LVEF&#xD;
&#xD;
          -  ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: Patients must have a Karnofsky&#xD;
             performance status of &gt;= 60%. Patients with CNS lymphoma with KPS of &gt;= 50% are&#xD;
             eligible if performance status is low because of the active lymphoma&#xD;
&#xD;
          -  ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: Measurable disease that can be&#xD;
             accurately measured in at least one dimension as &gt;= 1.5 cm with CT, ultrasound, or MRI&#xD;
             techniques; extranodal disease that is measurable by FDG-PET imaging only will also be&#xD;
             allowed; note that if an excisional biopsy was performed that removed the sole site of&#xD;
             measurable disease, the patient is not be eligible for lymphodepletion and CAR T cell&#xD;
             infusion; measurable disease can be based on the imaging study done during the&#xD;
             screening unless the patient received treatment in the interim, in which case imaging&#xD;
             should be repeated. For patients with CNS lymphoma, a lesion &gt;= 1 cm on the brain or&#xD;
             spine MRI is required. Patients with WM without radiologic evidence of disease are&#xD;
             eligible if they have measurable disease, as defined by serum IgM level &gt;= 0.5g/dL&#xD;
&#xD;
          -  ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: Patients must require no corticosteroid&#xD;
             therapy or dose of less than 15 mg per day of prednisone or the equivalent; pulsed&#xD;
             corticosteroid dose for disease control is acceptable until the day before the start&#xD;
             of lymphodepletion&#xD;
&#xD;
          -  ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: Patients must have no active acute or&#xD;
             chronic GVHD&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Active autoimmune disease requiring systemic immunosuppressive therapy&#xD;
&#xD;
          -  Patients requiring corticosteroid therapy at a dose of 15 mg or more per day of&#xD;
             prednisone or the equivalent; pulsed corticosteroid dose for disease control is&#xD;
             acceptable&#xD;
&#xD;
          -  Patients who are human immunodeficiency virus (HIV) seropositive&#xD;
&#xD;
          -  Women who are pregnant or breastfeeding&#xD;
&#xD;
          -  Significant cardiovascular diseases within the past 6 months including uncontrolled&#xD;
             congestive heart failure (&gt; New York Heart Association [NYHA] class II), myocardial&#xD;
             infarction, unstable angina, or uncontrolled arrhythmia&#xD;
&#xD;
          -  History of severe immediate hypersensitivity reaction to cyclophosphamide or&#xD;
             fludarabine&#xD;
&#xD;
          -  History or presence of clinically relevant non-lymphoma central nervous system&#xD;
             pathology, including seizures that are uncontrolled on anticonvulsant therapy (&gt;= 1&#xD;
             seizure in the last year), paresis, aphasia, stroke, severe brain injuries, dementia,&#xD;
             Parkinson disease, cerebellar disease, or psychosis&#xD;
&#xD;
          -  Treatment with any investigational agent on a different clinical trial within 4 weeks&#xD;
             prior to enrollment, unless the patient is documented to be unresponsive to the&#xD;
             therapy and at least 3 half-lives have elapsed prior to enrollment&#xD;
&#xD;
          -  Treatment with any anti-CD19 or anti-CD20 antibody or antibody-drug conjugate therapy&#xD;
             within 4 weeks before enrollment&#xD;
&#xD;
          -  Previous treatment with CD19-targeted CAR T cells that has resulted in ongoing B cell&#xD;
             aplasia at the time of enrollment; patients that demonstrate recovery of normal B&#xD;
             cells (&gt;= 20 B cells/ul) by flow cytometry at any point 28 days or later after CD19&#xD;
             CAR T cell infusion will be considered to have functional loss of CD19 CAR T cells and&#xD;
             are potentially eligible&#xD;
&#xD;
          -  Patients with systemic disease without radiologic evidence of CNS involvement and with&#xD;
             isolated CSF involvement detectable by flow cytometry are eligible for enrollment in&#xD;
             systemic disease cohorts if neurologically asymptomatic. CSF involvement is not an&#xD;
             exclusion for patients enrolled as a primary or secondary CNS lymphoma.&#xD;
&#xD;
          -  Presence of active acute or chronic graft versus host disease (GVHD)&#xD;
&#xD;
          -  Uncontrolled active infection (bacterial, fungal, viral, mycobacterial) not responding&#xD;
             to treatment with intravenous antibiotics, antiviral or antifungal agents&#xD;
&#xD;
          -  Patients with concurrent known additional malignancy that is progressing and/or&#xD;
             requires active treatment; exceptions include squamous or basal cell carcinoma of the&#xD;
             skin and low grade prostate carcinoma (Gleason grade =&lt; 6). Maintenance anti-hormone&#xD;
             therapies for breast or prostate cancers are allowed and are not considered active&#xD;
             treatment&#xD;
&#xD;
          -  Patients with blood or platelet transfusion within 1 week prior to signing Consent A,&#xD;
             or with platelets &lt; 50,000/mm^3, neutrophils &lt; 750/mm^3, or hemoglobin &lt; 8.5 g/dL,&#xD;
             unless the cytopenias are considered by the treating physician to be largely due to&#xD;
             marrow involvement by lymphoma&#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>Mazyar Shadman</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fred Hutch/University of Washington Cancer Consortium</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>SCCA Immunotherapy Intake</last_name>
    <phone>206-606-4668</phone>
    <email>immunotherapy@seattlecca.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>SCCA Immunotherapy Intake</last_name>
    <phone>855-557-0555</phone>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Fred Hutch/University of Washington Cancer Consortium</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>SCCA Immunotherapy Intake</last_name>
      <phone>206-606-4668</phone>
      <email>immunotherapy@seattlecca.org</email>
    </contact>
    <contact_backup>
      <last_name>SCCA Immunotherapy Intake</last_name>
      <phone>855-557-0555</phone>
    </contact_backup>
    <investigator>
      <last_name>Mazyar Shadman</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>September 7, 2017</study_first_submitted>
  <study_first_submitted_qc>September 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 11, 2017</study_first_posted>
  <last_update_submitted>May 4, 2023</last_update_submitted>
  <last_update_submitted_qc>May 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Lymphoid Leukemia</keyword>
  <keyword>Non-Hodgkin's Lymphoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Lymphoma, Follicular</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
    <mesh_term>Leukemia, Lymphoid</mesh_term>
    <mesh_term>Lymphoma, B-Cell</mesh_term>
    <mesh_term>Leukemia, Lymphocytic, Chronic, B-Cell</mesh_term>
    <mesh_term>Lymphoma, Mantle-Cell</mesh_term>
    <mesh_term>Lymphoma, B-Cell, Marginal Zone</mesh_term>
    <mesh_term>Lymphoma, Large B-Cell, Diffuse</mesh_term>
    <mesh_term>Waldenstrom Macroglobulinemia</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Fludarabine</mesh_term>
    <mesh_term>Fludarabine phosphate</mesh_term>
  </intervention_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/NCT03277729
org study id: 9738
secondary id: NCI-2017-01595
secondary id: 9738
secondary id: RG9217017
nct id: NCT03277729
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this research is to find the best dose of genetically modified T-cells, to
      study the safety of this treatment, and to see how well it works in treating patients with B
      cell non-Hodgkin lymphoma that has come back (relapsed) or did not respond to previous
      treatment (refractory).
OUTLINE:

      This is a phase I/II dose-escalation study of CD20-specific CAR T cell therapy.

      Patients undergo leukapheresis and may receive treatment after if needed for disease control.
      Patients then receive cyclophosphamide intravenously (IV). Patients may also receive
      fludarabine IV. After 36-96 hours, patients receive CD20-specific CAR T cell infusion IV over
      20-30 minutes.

      Patients will be actively participating in the study for approximately 15 months. The total
      time includes the time for the T cells to be made, the T cell infusion, and for approximately
      12 months after the T cell infusion is given. After completion of study treatment, patients
      are followed up for a minimum of 15 years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Dose-limiting toxicity
time frame: Up to 28 days
description: Will be graded by Common Terminology Criteria for Adverse Events version 4.0.
measure: Complete remission
time frame: Up to 15 years
description: Will be assessed based on the Lugano criteria.
measure: Progression-free survival (PFS)
time frame: Duration from study enrollment to progression or death due to any cause (whichever comes first), assessed up to 15 years
description: A Cox proportional hazards model will be used to evaluate PFS.
measure: Overall survival (OS)
time frame: Duration from study enrollment to death due to any cause, assessed up to 15 years
description: A Cox proportional hazards model will be used to evaluate OS.
measure: Incidence of adverse events
time frame: Up to 15 years
description: Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
arm group label: Treatment (CD20-specific CAR T cell, chemotherapy)
arm group type: Experimental
description: Patients undergo leukapheresis and may receive treatment after if needed for disease control. Patients then receive cyclophosphamide IV. Patients may also receive fludarabine IV. After 36-96 hours, patients receive CD20-specific CAR T cell infusion IV over 20-30 minutes.
intervention type: Biological
intervention name: Chimeric Antigen Receptor T-Cell Therapy
description: Given CD20 CAR T cell IV
arm group label: Treatment (CD20-specific CAR T cell, chemotherapy)
other name: CAR T-cell therapy
other name: CAR T Infusion
other name: CAR T Therapy
intervention type: Drug
intervention name: Cyclophosphamide
description: Given IV
arm group label: Treatment (CD20-specific CAR T cell, chemotherapy)
other name: (-)-Cyclophosphamide
other name: 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
other name: Carloxan
other name: Ciclofosfamida
other name: Ciclofosfamide
other name: Cicloxal
other name: Clafen
other name: Claphene
other name: CP monohydrate
other name: CTX
other name: CYCLO-cell
other name: Cycloblastin
other name: Cycloblastine
other name: Cyclophospham
other name: Cyclophosphamid monohydrate
other name: Cyclophosphamidum
other name: Cyclophosphan
other name: Cyclophosphane
other name: Cyclophosphanum
other name: Cyclostin
other name: Cyclostine
other name: Cytophosphan
other name: Cytophosphane
other name: Cytoxan
other name: Fosfaseron
other name: Genoxal
other name: Genuxal
other name: Ledoxina
other name: Mitoxan
other name: Neosar
other name: Revimmune
other name: Syklofosfamid
other name: WR- 138719
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment (CD20-specific CAR T cell, chemotherapy)
intervention type: Procedure
intervention name: Leukapheresis
description: Undergo leukapheresis
arm group label: Treatment (CD20-specific CAR T cell, chemotherapy)
other name: Leukocytopheresis
other name: Therapeutic Leukopheresis
intervention type: Drug
intervention name: Fludarabine Phosphate
description: Given IV
arm group label: Treatment (CD20-specific CAR T cell, chemotherapy)
other name: 2-F-ara-AMP
other name: Beneflur
other name: Fludara
other name: Fludarabine-5''-Monophosphate
other name: SH T 586
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Mazyar Shadman
role: Principal Investigator
affiliation: Fred Hutch/University of Washington Cancer Consortium
last name: SCCA Immunotherapy Intake
phone: 206-606-4668
email: immunotherapy@seattlecca.org
last name: SCCA Immunotherapy Intake
phone: 855-557-0555
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Leukemia
mesh term: Lymphoma, Follicular
mesh term: Lymphoma, Non-Hodgkin
mesh term: Leukemia, Lymphoid
mesh term: Lymphoma, B-Cell
mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
mesh term: Lymphoma, Mantle-Cell
mesh term: Lymphoma, B-Cell, Marginal Zone
mesh term: Lymphoma, Large B-Cell, Diffuse
mesh term: Waldenstrom Macroglobulinemia
mesh term: Recurrence
mesh term: Cyclophosphamide
mesh term: Fludarabine
mesh term: Fludarabine phosphate
sharing ipd: No