xml: <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/NCT05990465</url>
    </required_header>
    <id_info>
      <org_study_id>IIT-SHAH-FURQAN-LV20-19</org_study_id>
      <nct_id>NCT05990465</nct_id>
    </id_info>
    <brief_title>LV20.19 CAR T-Cells in Combination With Pirtobrutinib for Relapsed, Refractory B-cell Malignancies</brief_title>
    <official_title>Phase I Study of LV20.19 CAR T-cells in Combination With Pirtobrutinib for Relapsed, Refractory B-cell Malignancies</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Medical College of Wisconsin</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Medical College of Wisconsin</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This is a phase I, interventional, single arm, open label, treatment study designed to&#xD;
        evaluate the safety and efficacy of LV20.19 CAR -T cells with pirtobrutinib bridging and&#xD;
        maintenance in adult patients with B cell malignancies that have failed prior therapies.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is the first study to evaluate the safety and impact of the combination of pirtobrutinib&#xD;
        and LV20.19 CAR-T cells.&#xD;
  &#xD;
        Pirtobrutinib is a first-in-class non-covalent Bruton's tyrosine kinase (BTK) inhibitor. The&#xD;
        safe dose of this agent has been identified the BRUIN study as 200 mg daily administered as&#xD;
        an oral agent. As a single agent, the toxicity profile has been favorable and does not&#xD;
        overlap with other covalent BTK inhibitors with minimal cardiotoxicity and bleeding&#xD;
        complications.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">February 2025</completion_date>
    <primary_completion_date type="Anticipated">November 2024</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <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>Number of Adverse Events After CAR 20/19-T Cell Infusion</measure>
      <time_frame>Up until 28 days after infusion</time_frame>
      <description>This measure is the number of adverse events with grade 3 to 5 severity per Common Terminology Criteria for Adverse Events (ver. 5) occurring during the first 28 days following infusion.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of Adverse Events After Pirtobrutinib Administration in Part A</measure>
      <time_frame>14 days prior to apheresis until the start of lymphodepletion</time_frame>
      <description>Pirtobrutinib will be administered at 200 mg/day orally starting at least 14 days prior to apheresis as bridging until the start of lymphodepletion. This measure is the number of adverse events with grade 3 to 5 severity per Common Terminology Criteria for Adverse Events (ver. 5).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of Adverse Events After Pirtobrutinib Administration in Part B</measure>
      <time_frame>Day 28 until up to one year</time_frame>
      <description>Pirtobrutinib will be started again at 200 mg/day orally on day 28-120 for up to one year as maintenance post cell infusion. This measure is the number of adverse events with grade 3 to 5 severity per Common Terminology Criteria for Adverse Events (ver. 5).</description>
    </primary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">12</enrollment>
    <condition>Non Hodgkin Lymphoma</condition>
    <condition>Diffuse Large B Cell Lymphoma</condition>
    <condition>Follicular Lymphoma</condition>
    <condition>Marginal Zone Lymphoma</condition>
    <condition>Mantle Cell Lymphoma</condition>
    <condition>Burkitt Lymphoma</condition>
    <arm_group>
      <arm_group_label>Pirtobrutinib and CAR T Cells</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Pirtobrutinib is an oral agent. LV20.19 CAR T cells will be administered either fresh or thawed after cryopreservation by IV injection.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Pirtobrutinib</intervention_name>
      <description>Pirtobrutinib will be administered at 200 mg/day orally starting at least 14 days prior to apheresis as bridging until the start of lymphodepletion and restarted between day 28-120 for up to one year as maintenance post cell infusion.</description>
      <arm_group_label>Pirtobrutinib and CAR T Cells</arm_group_label>
      <other_name>Jaypirca</other_name>
      <other_name>LOXO-305</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>LV20.19 CAR T cells</intervention_name>
      <description>Subjects will receive a dose of 2.5x10^6 CAR-T cells/kg as a previously identified safe in a Phase 1 protocol at the Medical College of Wisconsin.</description>
      <arm_group_label>Pirtobrutinib and CAR T Cells</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          To facilitate rapid start of pirtobrutinib, there will be separate inclusion/exclusion for&#xD;
          pirtobrutinib and LV20.19 CAR T-cells in addition to the general inclusion as outlined&#xD;
          below.&#xD;
  &#xD;
          General inclusion criteria for trial:&#xD;
  &#xD;
            1. Patients must be aged ≥18 years and &lt;81 years with relapsed or refractory B-cell&#xD;
               non-Hodgkin Lymphoma (NHL).&#xD;
  &#xD;
            2. Diagnosis of relapsed or refractory B-cell NHL including Follicular Lymphoma, Marginal&#xD;
               Zone Lymphoma (splenic, nodal, extranodal), Mantle Cell Lymphoma, Burkitt Lymphoma and&#xD;
               DLBCL with associated subtypes (aggressive B-cell lymphoma, high grade B-cell&#xD;
               lymphoma, T-cell/histocyte rich B-cell lymphoma, primary mediastinal B-cell lymphoma,&#xD;
               Epstein-Barr virus-positive (EBV)+ diffuse large B-cell lymphoma, transformed lymphoma&#xD;
               such as transformed follicular or marginal zone, and Richter's transformation).&#xD;
  &#xD;
            3. Disease specific criteria as follows:&#xD;
  &#xD;
                 1. DLBCL and associated subtypes (listed above)&#xD;
  &#xD;
               i. Must have received Rituximab or another cluster of differentiation 20 (CD20)&#xD;
               antibody with combination anthracycline based chemotherapy regimen and have ONE of the&#xD;
               following:&#xD;
  &#xD;
            1. Primary refractory lymphoma or early relapse ≤6 months after one line of therapy.&#xD;
  &#xD;
            2. For relapse &gt;6.00 months, failure of two different chemotherapy regimens appropriate&#xD;
               for their disease and be ineligible to receive autologous transplant.&#xD;
  &#xD;
          ii. Relapse post-autologous transplant. iii. Relapse post-allogeneic transplant. iv.&#xD;
          Relapse post-CAR T-cell therapy (maximum 2 patients allowed with this designation).&#xD;
  &#xD;
          b. Mantle Cell Lymphoma&#xD;
  &#xD;
          i. Must have received Rituximab or another CD 20 antibody with one chemotherapy regimen&#xD;
          appropriate for this disease (bendamustine or cytarabine, or anthracycline based treatment)&#xD;
          and have ONE of the following:&#xD;
  &#xD;
            1. Relapsed disease after two lines of cytotoxic chemotherapy including administration of&#xD;
               anti-CD20 antibody.&#xD;
  &#xD;
            2. Progressive disease after ≥second line BTK inhibitor.&#xD;
  &#xD;
            3. Relapse post-autologous transplant.&#xD;
  &#xD;
            4. Relapse post-allogeneic transplant.&#xD;
  &#xD;
               c. Marginal Zone Lymphoma and Follicular Lymphoma&#xD;
  &#xD;
               i. Must have received Rituximab or another CD20 antibody with chemotherapy regimen&#xD;
               appropriate for the disease and have ONE of the following:&#xD;
  &#xD;
            1. Relapsed disease after two lines of therapy including administration of anti-CD20&#xD;
               antibody.&#xD;
  &#xD;
            2. Relapse post-autologous transplant.&#xD;
  &#xD;
            3. Relapse post-allogeneic transplant.&#xD;
  &#xD;
               d. Burkitt's Lymphoma&#xD;
  &#xD;
               i. Must have received Rituximab or another CD20 antibody in combination with&#xD;
               anthracycline based chemotherapy regimen and have ONE of the following:&#xD;
  &#xD;
            1. Primary refractory lymphoma.&#xD;
  &#xD;
            2. Relapse within 6 months.&#xD;
  &#xD;
            3. For relapse &gt;6 months, failure of two different chemotherapy regimens appropriate for&#xD;
               their disease and be ineligible to receive autologous transplant.&#xD;
  &#xD;
               i. Relapse post-autologous transplant. ii. Relapse post-allogeneic transplant.&#xD;
  &#xD;
            4. Able to provide written informed consent.&#xD;
  &#xD;
            5. Negative urine or serum pregnancy test in females of childbearing potential at&#xD;
               screening.&#xD;
  &#xD;
            6. Willingness of women of reproductive potential and their partners to observe highly&#xD;
               effective birth control methods for duration of treatment and for 1 month following&#xD;
               the last dose if study treatment.&#xD;
  &#xD;
            7. Karnofsky performance score ≥70.&#xD;
  &#xD;
            8. Expected survival &gt;12 weeks.&#xD;
  &#xD;
            9. Patient has demonstrated compliance with prior therapies.&#xD;
  &#xD;
           10. Able to take oral medications.&#xD;
  &#xD;
           11. Adequate coagulation, defined as activated partial thromboplastin time (aPTT) or&#xD;
               partial thromboplastin time (PTT) and prothrombin (PT) or (international normalized&#xD;
               ratio (INR) not greater than 1.5 x upper limit of normal (ULN).&#xD;
  &#xD;
           12. Patients are required to have the following washout periods prior to planned Cycle 1&#xD;
               Day 1 (C1D1). In addition, prior treatment-related adverse events (AEs) must have&#xD;
               recovered to Grade ≤ 1 with the exception of alopecia and Grade 2 peripheral&#xD;
               neuropathy.&#xD;
  &#xD;
                 1. Targeted agents, investigational agents, therapeutic monoclonal antibodies or&#xD;
                    cytotoxic chemotherapy: 5 half-lives or 2 weeks, whichever is shorter.&#xD;
  &#xD;
                 2. immunoconjugated antibody treatment within 10 weeks prior to randomization.&#xD;
  &#xD;
                 3. broad field radiation (≥ 30% of the bone marrow or whole brain radiotherapy) must&#xD;
                    be completed 14 days prior to study enrollment.&#xD;
  &#xD;
                 4. palliative limited field radiation must be completed 7 days prior to study&#xD;
                    enrollment.&#xD;
  &#xD;
          Inclusion Criteria to START Pirtobrutinib Bridging:&#xD;
  &#xD;
            1. Absolute neutrophil count (ANC) ≥1000 with no G-CSF within 7 days or pegylated G-CSF&#xD;
               within 14 days unless patient has biopsy proven bone marrow involvement.&#xD;
  &#xD;
            2. Platelets≥50,000 with no transfusion within 7 days unless patient has biopsy proven&#xD;
               bone marrow involvement.&#xD;
  &#xD;
            3. Hemoglobin ≥8g/dL (≥80 g/L) [blood transfusions are allowable to reach this goal].&#xD;
  &#xD;
            4. Adequate hepatic function, defined as aspartate aminotransferase (AST) and alanine&#xD;
               transaminase (ALT) &lt;3 x upper limit of normal (ULN) or &lt; 5 x ULN with documented liver&#xD;
               involvement; serum bilirubin &lt;1.5 x ULN or &lt;3 x ULN with documented liver involvement&#xD;
               , or considered not clinically significant as per the clinical PIs discretion (e.g.&#xD;
               Gilbert's or indirect hyperbilirubinemia) or felt to be due to underlying disease.&#xD;
  &#xD;
            5. Adequate renal function, defined as creatinine clearance≥50 ml/min.&#xD;
  &#xD;
                 1. No IV hydration within 24 hours of eligibility.&#xD;
  &#xD;
                 2. No dialysis dependent renal failure.&#xD;
  &#xD;
          Inclusion criteria for Pirtobrutinib Maintenance (part B)&#xD;
  &#xD;
            1. Recovery of neutrophils count after CAR T-cell infusion with ANC ≥1000/dL without&#xD;
               G-CSF within the last 7 days.&#xD;
  &#xD;
            2. Recovery of platelet count after CAR T-cell infusion with platelet count ≥50,000/dL.&#xD;
  &#xD;
            3. Adequate hepatic function, defined as back to baseline or AST and ALT &lt;3 x upper limit&#xD;
               of normal (ULN); serum bilirubin and alkaline phosphatase &lt;3 x ULN, or considered not&#xD;
               clinically significant as per the clinical PI's discretion (e.g., Gilbert's or&#xD;
               indirect hyperbilirubinemia) or felt to be due to underlying disease.&#xD;
  &#xD;
            4. Adequate renal function, defined as creatinine clearance≥40 ml/min.&#xD;
  &#xD;
            5. Evidence of response or stable disease (complete response/partial response/stable&#xD;
               disease) at day 28 after CAR T-cell therapy.&#xD;
  &#xD;
          Inclusion Criteria for Apheresis and LV20.19 CAR T-cells:&#xD;
  &#xD;
            1. Active Measurable disease must be documented within 4 weeks of lymphodepletion start&#xD;
               defined as nodal lesions greater than 15 mm in the long axis or extranodal lesions &gt;10&#xD;
               mm in long and short axis OR bone marrow involvement that is biopsy proven for B-cell&#xD;
               NHL.&#xD;
  &#xD;
            2. Absolute cluster of differentiation (CD) 3 count≥50 mm^3.&#xD;
  &#xD;
            3. MRI brain and Lumbar Puncture with cerebrospinal fluid (CSF) analysis by cytology and&#xD;
               flow cytometry without evidence of central nervous system (CNS) involvement ONLY in&#xD;
               patients with history of CNS involvement or clinical suspicion at the time of&#xD;
               enrollment.&#xD;
  &#xD;
            4. Adequate cardiac function as indicated by New York Heart Association (NYHA)&#xD;
               classification I or II AND left ventricular ejection fraction of ≥45% (by&#xD;
               echocardiogram (ECHO) or MUGA) and adequate pulmonary function as indicated by room&#xD;
               air oxygen saturation of ≥92%.&#xD;
  &#xD;
            5. No contraindication to central line access.&#xD;
  &#xD;
            6. ANC≥1000 with no pegylated G-CSF within 14 days unless patient has biopsy proven bone&#xD;
               marrow involvement.&#xD;
  &#xD;
            7. Platelets≥50,000 with no transfusion within 72 hours unless patient has biopsy proven&#xD;
               bone marrow involvement.&#xD;
  &#xD;
            8. Adequate hepatic function, defined as AST and ALT &lt;3 x upper limit of normal (ULN);&#xD;
               serum bilirubin and alkaline phosphatase &lt;3 x ULN, or considered not clinically&#xD;
               significant as per the clinical PIs discretion (e.g. Gilbert's or indirect&#xD;
               hyperbilirubinemia) or felt to be due to underlying disease.&#xD;
  &#xD;
            9. Adequate renal function, defined as creatinine clearance≥50 ml/min. a. No IV hydration&#xD;
               within 24 hours of eligibility. b. No dialysis dependent renal failure.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          A potential subject who meets any of the following exclusion criteria is ineligible to&#xD;
          participate in the study.&#xD;
  &#xD;
            1. Positive beta-human chorionic gonadotropin (HCG) in female of child-bearing potential&#xD;
               or plan to become pregnant during the study or within 1 month of the last dose of&#xD;
               study treatment and women who are current lactating or plan to breastfeed during the&#xD;
               study or within 1 week of the last dose of study treatment.&#xD;
  &#xD;
            2. Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection based on&#xD;
               criteria below:&#xD;
  &#xD;
                 1. HBV: Patients with positive hepatitis B surface antigen (HBsAg) are excluded.&#xD;
                    Patients with positive hepatitis B core antibody (anti-HBc) and negative HBsAg&#xD;
                    require hepatitis B polymerase chain reaction (PCR) evaluation before&#xD;
                    randomization. Patients who are hepatitis B PCR positive will be excluded.&#xD;
  &#xD;
                 2. Hepatitis C virus (HCV): positive hepatitis C antibody. If positive hepatitis C&#xD;
                    antibody result, patient will need to have a negative result for hepatitis C&#xD;
                    ribonucleic acid (RNA) before randomization. Patients who are hepatitis C RNA&#xD;
                    positive will be excluded.&#xD;
  &#xD;
            3. Known active cytomegalovirus (CMV) infection (Unknown or negative status are&#xD;
               eligible).&#xD;
  &#xD;
            4. History of significant autoimmune disease OR active, uncontrolled autoimmune&#xD;
               phenomenon requiring steroid therapy defined as &gt;20 mg of prednisone or equivalent&#xD;
               daily.&#xD;
  &#xD;
            5. Presence of ≥ grade 3 non-hematologic toxicities as per CTCAE version 5.0 from any&#xD;
               previous treatment unless it is felt to be due to underlying disease.&#xD;
  &#xD;
            6. Concurrent use of investigational therapeutic agents or enrollment on another&#xD;
               therapeutic clinical trial at any institution. Minimum of 14 days or 5 half-lives of&#xD;
               the drug (whichever is shorter) washout prior to apheresis.&#xD;
  &#xD;
            7. Refusal to participate in the long-term follow-up protocol.&#xD;
  &#xD;
            8. Patients with active CNS involvement by malignancy on MRI or by lumbar puncture.&#xD;
  &#xD;
                 1. Patients with prior CNS disease that has been effectively treated will be&#xD;
                    eligible providing treatment was &gt;4 weeks before enrollment and a remission&#xD;
                    documented within 8 weeks of planned CAR-T cell infusion by MRI brain and CSF&#xD;
                    analysis.&#xD;
  &#xD;
            9. Previous recipients of allogeneic hematopoietic stem cell transplantation (AHCT) are&#xD;
               excluded if they are &lt;100 days post-transplant, have evidence of active&#xD;
               graft-versus-host-disease (GVHD) of any grade, or are currently on immunosuppression.&#xD;
  &#xD;
           10. Prior allogeneic CAR T-cell therapy &lt;100 days from prior CAR T-cell treatment.&#xD;
  &#xD;
           11. Previous recipients of autologous CAR-T cell therapy directed at either cluster of&#xD;
               differentiation 19 (CD19) or CD20 are excluded if they are &lt;100 days post prior CAR-T&#xD;
               cell treatment (does not include re-enrollment) or have &gt;5% residual circulating CAR-T&#xD;
               as measured by flow cytometry using a CD19 CAR detection reagent (Miltenyi Biotec).&#xD;
  &#xD;
               a. Patients with prior CAR-T treatment against CD19 or CD20 must have repeat biopsy&#xD;
               post-CAR-T cell therapy confirming a minimum of 5% CD19 or CD20 positivity by&#xD;
               immunohistochemistry or flow cytometry.&#xD;
  &#xD;
           12. Anti-CD20 antibody treatment within 4 weeks of cell infusion.&#xD;
  &#xD;
           13. Anti-CD19 antibody treatment within 4 weeks of cell infusion.&#xD;
  &#xD;
           14. Cytotoxic chemotherapy treatment within 14 days or steroid treatment (other than&#xD;
               replacement dose steroids) within 7 days prior to apheresis collection for CAR-T&#xD;
               cells.&#xD;
  &#xD;
           15. No other oral chemotherapeutic agents or antibody directed treatment after starting&#xD;
               pirtobrutinib other than steroids or radiation to a single site in a palliative&#xD;
               fashion.&#xD;
  &#xD;
           16. Patients post solid organ transplant who develop high grade lymphomas or leukemias.&#xD;
  &#xD;
           17. Concurrent active malignancy other than basal or squamous cell carcinomas of the skin&#xD;
               (underlying low-grade lymphoma chronic lymphocytic leukemia/Follicular lymphoma (FL) /&#xD;
               Marginal zone lymphoma (MZL) is allowable in patients with transformed large cell&#xD;
               lymphoma/Richter's.&#xD;
  &#xD;
           18. Patients who experienced a major bleeding event or grade ≥ 3 arrhythmia on prior&#xD;
               treatment with a BTK inhibitor.&#xD;
  &#xD;
           19. History of stroke or intracranial hemorrhage within 6 months of randomization.&#xD;
  &#xD;
           20. Significant cardiovascular disease defined as myocardial infarction within 6 months of&#xD;
               randomization, congestive heart failure with ejection fraction &lt;30%, active unstable&#xD;
               angina, QT prolongation (QTcF)&gt;470 msec on ECG.&#xD;
  &#xD;
           21. Clinically significant active malabsorption syndrome or other condition likely to&#xD;
               affect gastrointestinal (GI) absorption of the study drug.&#xD;
  &#xD;
           22. Patients requiring therapeutic anticoagulation with warfarin or another vitamin K&#xD;
               antagonist.&#xD;
  &#xD;
           23. Patients who had surgery within 4 weeks prior to randomization.&#xD;
  &#xD;
           24. Patients who have received vaccination with live vaccine within 28 days prior to&#xD;
               randomization.&#xD;
  &#xD;
           25. Patients with known hypersensitivity to any of the excipients of pirtobrutinib.&#xD;
  &#xD;
               Special Criteria Regarding Fertility and Contraception&#xD;
  &#xD;
               Female subjects of reproductive potential (women who have reached menarche or women&#xD;
               who have not been post-menopausal for at least 24 consecutive months, i.e., who have&#xD;
               had menses within the preceding 24 months, or have not undergone a sterilization&#xD;
               procedure [hysterectomy or bilateral oophorectomy]) must have a negative serum or&#xD;
               urine pregnancy test performed at screening.&#xD;
  &#xD;
               Due to the high-risk level of this study, while enrolled, all subjects must agree not&#xD;
               to participate in a conception process (e.g., active attempt to become pregnant or to&#xD;
               impregnate, sperm donation, in vitro fertilization). Additionally, if participating in&#xD;
               sexual activity that could lead to pregnancy, the study subject must agree to use&#xD;
               reliable and double barrier methods of contraception during the follow-up period of&#xD;
               the protocol.&#xD;
  &#xD;
               Acceptable birth control includes a combination of two of the following methods:&#xD;
  &#xD;
               • Combined estrogen and progestin containing hormonal contraception associated with&#xD;
               inhibition of ovulation given orally, intravaginally, or transdermally&#xD;
  &#xD;
               • Progestin-only hormonal contraception associated with inhibition of ovulation given&#xD;
               orally, by injection, or by implant&#xD;
  &#xD;
               • Intrauterine device (IUD)&#xD;
  &#xD;
               • Intrauterine hormone-releasing system (IUS)&#xD;
  &#xD;
               • Vasectomized partner&#xD;
  &#xD;
               • Sexual abstinence: considered a highly effective method only if defined as&#xD;
               refraining from heterosexual intercourse during an entire period of risk associated&#xD;
               with the study treatment. The reliability of sexual abstinence will be evaluated in&#xD;
               relation to the duration of the study and to the usual lifestyles of the patient.&#xD;
  &#xD;
               • Female sterilization&#xD;
  &#xD;
               • Fallopian tube implants (if confirmed by hysterosalpingogram) Oocyte donation is&#xD;
               prohibited during the duration of participation on this protocol and for 1 month after&#xD;
               the last dose of study drug.&#xD;
  &#xD;
               Subjects who are not of reproductive potential (women who are premenarche or have been&#xD;
               post-menopausal for at least 24 consecutive months which is non-therapy induced or&#xD;
               have undergone hysterectomy tubal ligation, salpingectomy, and/or bilateral&#xD;
               oophorectomy or men who have documented azoospermia) are eligible without requiring&#xD;
               the use of contraception.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>81 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Nirav Shah, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Medical College of Wisconsin</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Medical College of Wisconsin Cancer Center Clinical Trials Office</last_name>
      <phone>866-680-0505</phone>
      <phone_ext>8900</phone_ext>
      <email>cccto@mcw.edu</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 4, 2023</study_first_submitted>
    <study_first_submitted_qc>August 4, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 4, 2023</last_update_submitted>
    <last_update_submitted_qc>August 4, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Medical College of Wisconsin</investigator_affiliation>
      <investigator_full_name>Nirav Shah</investigator_full_name>
      <investigator_title>Associate Professor</investigator_title>
    </responsible_party>
    <keyword>CAR-T</keyword>
    <keyword>Chimeric antigen receptor T-cell therapy</keyword>
    <keyword>CAR Therapy</keyword>
    <keyword>Pirtobrutinib</keyword>
    <keyword>B Cells</keyword>
    <keyword>BTK inhibitor</keyword>
    <keyword>Bruton's tyrosine kinase</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>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>Pirtobrutinib</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05990465
  org study id: IIT-SHAH-FURQAN-LV20-19
  nct id: NCT05990465
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  This is a phase I, interventional, single arm, open label, treatment study designed to
        evaluate the safety and efficacy of LV20.19 CAR -T cells with pirtobrutinib bridging and
        maintenance in adult patients with B cell malignancies that have failed prior therapies.
  This is the first study to evaluate the safety and impact of the combination of pirtobrutinib
        and LV20.19 CAR-T cells.
  
        Pirtobrutinib is a first-in-class non-covalent Bruton's tyrosine kinase (BTK) inhibitor. The
        safe dose of this agent has been identified the BRUIN study as 200 mg daily administered as
        an oral agent. As a single agent, the toxicity profile has been favorable and does not
        overlap with other covalent BTK inhibitors with minimal cardiotoxicity and bleeding
        complications.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Number of Adverse Events After CAR 20/19-T Cell Infusion
  time frame: Up until 28 days after infusion
  description: This measure is the number of adverse events with grade 3 to 5 severity per Common Terminology Criteria for Adverse Events (ver. 5) occurring during the first 28 days following infusion.
  measure: Number of Adverse Events After Pirtobrutinib Administration in Part A
  time frame: 14 days prior to apheresis until the start of lymphodepletion
  description: Pirtobrutinib will be administered at 200 mg/day orally starting at least 14 days prior to apheresis as bridging until the start of lymphodepletion. This measure is the number of adverse events with grade 3 to 5 severity per Common Terminology Criteria for Adverse Events (ver. 5).
  measure: Number of Adverse Events After Pirtobrutinib Administration in Part B
  time frame: Day 28 until up to one year
  description: Pirtobrutinib will be started again at 200 mg/day orally on day 28-120 for up to one year as maintenance post cell infusion. This measure is the number of adverse events with grade 3 to 5 severity per Common Terminology Criteria for Adverse Events (ver. 5).
  arm group label: Pirtobrutinib and CAR T Cells
  arm group type: Experimental
  description: Pirtobrutinib is an oral agent. LV20.19 CAR T cells will be administered either fresh or thawed after cryopreservation by IV injection.
  intervention type: Drug
  intervention name: Pirtobrutinib
  description: Pirtobrutinib will be administered at 200 mg/day orally starting at least 14 days prior to apheresis as bridging until the start of lymphodepletion and restarted between day 28-120 for up to one year as maintenance post cell infusion.
  arm group label: Pirtobrutinib and CAR T Cells
  other name: Jaypirca
  other name: LOXO-305
  intervention type: Drug
  intervention name: LV20.19 CAR T cells
  description: Subjects will receive a dose of 2.5x10^6 CAR-T cells/kg as a previously identified safe in a Phase 1 protocol at the Medical College of Wisconsin.
  arm group label: Pirtobrutinib and CAR T Cells
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 81 Years
  healthy volunteers: No
  last name: Nirav Shah, MD
  role: Principal Investigator
  affiliation: Medical College of Wisconsin
  last name: Medical College of Wisconsin Cancer Center Clinical Trials Office
  phone: 866-680-0505
  phone ext: 8900
  email: cccto@mcw.edu
  responsible party type: Principal Investigator
  investigator affiliation: Medical College of Wisconsin
  investigator full name: Nirav Shah
  investigator title: Associate Professor
  mesh term: Burkitt Lymphoma
  mesh term: Lymphoma
  mesh term: Lymphoma, Mantle-Cell
  mesh term: Lymphoma, Large B-Cell, Diffuse
  mesh term: Pirtobrutinib
  sharing ipd: No