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/NCT06015880</url>
    </required_header>
    <id_info>
      <org_study_id>NCI-2023-06477</org_study_id>
      <secondary_id>NCI-2023-06477</secondary_id>
      <secondary_id>PHI-141</secondary_id>
      <secondary_id>10601</secondary_id>
      <secondary_id>10601</secondary_id>
      <secondary_id>UM1CA186717</secondary_id>
      <nct_id>NCT06015880</nct_id>
    </id_info>
    <brief_title>Testing the Combination of Anti-cancer Drugs Mosunetuzumab, Polatuzumab Vedotin, and Lenalidomide for the Treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma</brief_title>
    <official_title>A Phase 1 Study of Mosunetuzumab With Polatuzumab Vedotin and Lenalidomide (M+Pola+Len) in Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>National Cancer Institute (NCI)</agency>
        <agency_class>NIH</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>National Cancer Institute (NCI)</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        This phase I trial studies the side effects and best dose of mosunetuzumab when given&#xD;
        together with polatuzumab vedotin and lenalidomide in treating patients with diffuse large&#xD;
        B-cell lymphoma (DLBCL) that has come back after a period of improvement (relapsed) or that&#xD;
        has not responded to previous treatment (refractory). Mosunetuzumab and polatuzumab vedotin&#xD;
        are monoclonal antibodies that may interfere with the ability of cancer cells to grow and&#xD;
        spread. Polatuzumab, linked to a toxic agent called vedotin, attaches to CD79B positive&#xD;
        cancer cells in a targeted way and delivers vedotin to kill them. Lenalidomide may stimulate&#xD;
        or suppress the immune system in different ways and stop cancer cells from growing and by&#xD;
        preventing the growth of new blood vessels that cancer cells need to grow. Giving&#xD;
        mosunetuzumab with polatuzumab vedotin and lenalidomide may work better in treating patients&#xD;
        with relapsed/refractory DLBCL.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        PRIMARY OBJECTIVE:&#xD;
  &#xD;
        I. To determine the safety and tolerability of mosunetuzumab + polatuzumab vedotin +&#xD;
        lenalidomide in relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL).&#xD;
  &#xD;
        SECONDARY OBJECTIVE:&#xD;
  &#xD;
        I. To observe and record anti-tumor activity of the combination of mosunetuzumab, polatuzumab&#xD;
        vedotin, and lenalidomide in R/R DLBCL.&#xD;
  &#xD;
        EXPLORATORY OBJECTIVES:&#xD;
  &#xD;
        I. To assess the efficacy in patients that have failed prior polatuzumab vedotin containing&#xD;
        regimens (i.e., patients who progressed/relapsed after prior polatuzumab).&#xD;
  &#xD;
        II. To assess anti-tumor activity in patients that a) have &lt; complete response (CR) or&#xD;
        Deauville score of 3 or worse at day 90 (D90) (or before) after standard of care chimeric&#xD;
        antigen receptor (CAR) T-cell therapy; b) other patients who have failed prior treatment&#xD;
        (e.g. relapse after day 90 from CAR-T, or relapsed after other therapies and were not&#xD;
        considered candidates for CAR-T).&#xD;
  &#xD;
        III. To identify biomarkers that can predict the response to mosunetuzumab + polatuzumab&#xD;
        vedotin + lenalidomide.&#xD;
  &#xD;
        IV. To describe anti-tumor activity in patients whose tumors have previously failed to&#xD;
        respond to polatuzumab (i.e., patients who progressed/relapsed after prior polatuzumab).&#xD;
  &#xD;
        OUTLINE: This is a dose-escalation study of mosunetuzumab, followed by a dose-expansion&#xD;
        study.&#xD;
  &#xD;
        Patients receive mosunetuzumab intravenously (IV) over 2-4 hours on days 1, 8, and 15 of&#xD;
        cycle 1 and then day 1 of each subsequent cycle. Treatment repeats every 28 days for 8 cycles&#xD;
        in patients who achieve a complete response (CR) or up to 17 cycles for patients with a&#xD;
        partial response (PR) or stable disease (SD) in the absence of disease progression or&#xD;
        unacceptable toxicity. Patients also recieve polatuzumab vedotin IV over 30-90 minutes on day&#xD;
        1 for 6 cycles and lenalidomide orally (PO) on days 1-21 for 8 cycles in patients who achieve&#xD;
        CR or up to 17 cycles. Cycles repeat every 28 days in the absence of disease progression or&#xD;
        unacceptable toxicity. Patients undergo positron emission tomography (PET)/ computed&#xD;
        tomography (CT) and blood sample collection throughout the study.&#xD;
  &#xD;
        After completion of study treatment, patients are followed up for 2 years.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">December 8, 2023</start_date>
    <completion_date type="Anticipated">May 1, 2025</completion_date>
    <primary_completion_date type="Anticipated">May 1, 2025</primary_completion_date>
    <phase>Phase 1</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>Safety and tolerability of monsunetuzumab+polatuzumab vedotin+lenalidomide for determination of recommended phase 2 dose</measure>
      <time_frame>During cycle 1 (cycle=28 days)</time_frame>
      <description>Dose limiting toxicity will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Objective response rate</measure>
      <time_frame>Up to 2 years</time_frame>
      <description>Will be assessed per the Lugano 2014 criteria.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Complete response rate</measure>
      <time_frame>Up to 2 years</time_frame>
      <description>Will be assessed per the Lugano 2014 criteria.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression free survival</measure>
      <time_frame>Up to 2 years</time_frame>
      <description>Will be assessed per the Lugano 2014 criteria.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of response</measure>
      <time_frame>From time of initial response assessment demonstrating at least partial response until disease response assessment that demonstrates progressive disease, assessed up to 2 years</time_frame>
      <description>Will be assessed per the Lugano 2014 criteria.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>CD79b expression levels</measure>
      <time_frame>At baseline</time_frame>
      <description>Will be assessed via ribonucleic acid and immunohistochemistry assessment and correlation with response.</description>
    </other_outcome>
    <other_outcome>
      <measure>Frequency of CD4 T-cells and IFN-gamma+ producing CD4 T-cells</measure>
      <time_frame>At baseline and up to 2 years</time_frame>
      <description>Will be assessed via intracellular flow cytometry.</description>
    </other_outcome>
    <other_outcome>
      <measure>Ultrasensitive determination of cytokine profile</measure>
      <time_frame>At baseline and up to 2 years</time_frame>
      <description>Will be assessed with Luminex assay to identify biomarkers that might predict a response.</description>
    </other_outcome>
    <other_outcome>
      <measure>Efficacy in relapsed/refractory double-expresser lymphoma and double-hit lymphoma</measure>
      <time_frame>Up to 2 years</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Efficacy post chimeric antigen receptor (CAR) T-cell therapy</measure>
      <time_frame>Up to 2 years</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Efficacy post polatuzumab vedotin</measure>
      <time_frame>Up to 2 years</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Percent of patients able to start the triplet therapy</measure>
      <time_frame>At cycle 2 (cycle=28 days)</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>CAR T-cell expansion and persistence</measure>
      <time_frame>Up to 2 years</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>CAR T-cell immunophenotypes</measure>
      <time_frame>Up to 2 years</time_frame>
    </other_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">30</enrollment>
    <condition>Diffuse Large B-Cell Lymphoma, Not Otherwise Specified</condition>
    <condition>High Grade B-Cell Lymphoma</condition>
    <condition>Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma</condition>
    <arm_group>
      <arm_group_label>Treatment (mosunetuzumab, polatuzumab vedotin, lenalidomide)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients receive mosunetuzumab IV over 2-4 hours on days 1, 8, and 15 of cycle 1 and then day 1 of each subsequent cycle. Treatment repeats every 28 days for 8 cycles in patients who achieve a CR or up to 17 cycles for patients with a PR or SD in the absence of disease progression or unacceptable toxicity. Patients also recieve polatuzumab vedotin IV over 30-90 minutes on day 1 for 6 cycles and lenalidomide PO on days 1-21 for 8 cycles in patients who achieve CR or up to 17 cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo PET/CT and blood sample collection throughout the study.</description>
    </arm_group>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Biospecimen Collection</intervention_name>
      <description>Undergo blood sample collection</description>
      <arm_group_label>Treatment (mosunetuzumab, polatuzumab vedotin, lenalidomide)</arm_group_label>
      <other_name>Biological Sample Collection</other_name>
      <other_name>Biospecimen Collected</other_name>
      <other_name>Specimen Collection</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Computed Tomography</intervention_name>
      <description>Undergo PET/CT</description>
      <arm_group_label>Treatment (mosunetuzumab, polatuzumab vedotin, lenalidomide)</arm_group_label>
      <other_name>CAT</other_name>
      <other_name>CAT Scan</other_name>
      <other_name>Computed Axial Tomography</other_name>
      <other_name>Computerized Axial Tomography</other_name>
      <other_name>Computerized axial tomography (procedure)</other_name>
      <other_name>Computerized Tomography</other_name>
      <other_name>CT</other_name>
      <other_name>CT Scan</other_name>
      <other_name>tomography</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Lenalidomide</intervention_name>
      <description>Given PO</description>
      <arm_group_label>Treatment (mosunetuzumab, polatuzumab vedotin, lenalidomide)</arm_group_label>
      <other_name>CC-5013</other_name>
      <other_name>CC5013</other_name>
      <other_name>CDC 501</other_name>
      <other_name>Revlimid</other_name>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Mosunetuzumab</intervention_name>
      <description>Given IV</description>
      <arm_group_label>Treatment (mosunetuzumab, polatuzumab vedotin, lenalidomide)</arm_group_label>
      <other_name>Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody BTCT4465A</other_name>
      <other_name>BTCT 4465A</other_name>
      <other_name>BTCT-4465A</other_name>
      <other_name>BTCT4465A</other_name>
      <other_name>CD20/CD3 BiMAb BTCT4465A</other_name>
      <other_name>Lunsumio</other_name>
      <other_name>Mosunetuzumab-axgb</other_name>
      <other_name>RG 7828</other_name>
      <other_name>RG-7828</other_name>
      <other_name>RG7828</other_name>
      <other_name>RO7030816</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Polatuzumab Vedotin</intervention_name>
      <description>Given IV</description>
      <arm_group_label>Treatment (mosunetuzumab, polatuzumab vedotin, lenalidomide)</arm_group_label>
      <other_name>ADC DCDS4501A</other_name>
      <other_name>Antibody-Drug Conjugate DCDS4501A</other_name>
      <other_name>DCDS4501A</other_name>
      <other_name>FCU 2711</other_name>
      <other_name>polatuzumab vedotin-piiq</other_name>
      <other_name>Polivy</other_name>
      <other_name>RG7596</other_name>
      <other_name>Ro 5541077-000</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Positron Emission Tomography</intervention_name>
      <description>Undergo PET/CT</description>
      <arm_group_label>Treatment (mosunetuzumab, polatuzumab vedotin, lenalidomide)</arm_group_label>
      <other_name>Medical Imaging, Positron Emission Tomography</other_name>
      <other_name>PET</other_name>
      <other_name>PET Scan</other_name>
      <other_name>Positron emission tomography (procedure)</other_name>
      <other_name>Positron Emission Tomography Scan</other_name>
      <other_name>Positron-Emission Tomography</other_name>
      <other_name>proton magnetic resonance spectroscopic imaging</other_name>
      <other_name>PT</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Patients must have histologically confirmed DLBCL NOS, high-grade B-cell lymphoma, or&#xD;
               transformed indolent lymphoma as per the World Health Organization 2022 criteria&#xD;
  &#xD;
            -  All patients will have relapsed/refractory DLBCL after 1 or more prior lines of&#xD;
               therapy with the exception of patients receiving CAR T in second line that have a D&#xD;
               score of 3 at day (D)+ 30 through D+ 90&#xD;
  &#xD;
            -  Patients who progressed/relapsed after prior polatuzumab vedotin are allowed&#xD;
  &#xD;
            -  For the expansion cohorts only: cohort A must have &lt; complete response (CR) or&#xD;
               Deauville score of 3 or 4 at D90 (or before) after standard of care chimeric antigen&#xD;
               receptor (CAR) T-cell therapy; cohort B- other patients with relapsed/refractory after&#xD;
               1 or more prior lines of therapy (e.g. relapse after day 90 from CAR-T, or relapsed&#xD;
               after other therapies and were not considered candidates for CAR-T or autologous&#xD;
               hematopoietic cell transplantation)&#xD;
  &#xD;
            -  All patients that have failed 1 line of therapy will be eligible with the exception of&#xD;
               a 12 patient cohort (A) that will require prior CAR T therapy&#xD;
  &#xD;
            -  Measurable disease by CT or PET scan, with one or more sites of disease &gt;= 1.5 cm in&#xD;
               longest dimension&#xD;
  &#xD;
            -  Age &gt;= 18 years&#xD;
  &#xD;
                 -  Because no dosing or adverse event data are currently available on the use of&#xD;
                    mosunetuzumab in combination with polatuzumab vedotin, and lenalidomide in&#xD;
                    patients &lt; 18 years of age, children are excluded from this study&#xD;
  &#xD;
            -  Eastern Cooperative Oncology Group (ECOG) performance status =&lt; 2 (Karnofsky &gt;= 60%)&#xD;
  &#xD;
            -  Life expectancy &gt;= 12 weeks&#xD;
  &#xD;
            -  Absolute neutrophil count &gt;= 1,000/mcL&#xD;
  &#xD;
            -  Platelets &gt;= 50,000/mcL without transfusion for 2 weeks prior to cycle 1 day 1 (C1D1)&#xD;
  &#xD;
            -  Hemoglobin &gt;= 9 g/dL&#xD;
  &#xD;
            -  Total bilirubin =&lt; 1.5 × institutional upper limit of normal (ULN) (however, patients&#xD;
               with known Gilbert disease who have serum bilirubin level =&lt; 3 × ULN may be enrolled)&#xD;
  &#xD;
            -  Aspartate transaminase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/ alanine&#xD;
               aminotransferase (ALT) (serum glutamic-pyruvic transaminase [SGPT]) =&lt; 3 × ULN (AST&#xD;
               and/or ALT =&lt; 5 × ULN for patients with liver involvement)&#xD;
  &#xD;
            -  Alkaline phosphatase 2.5 × ULN (=&lt; 5 × ULN for patients with documented liver&#xD;
               involvement or bone metastases)&#xD;
  &#xD;
            -  Creatinine clearance &gt;= 30 mL/min/1.73 m^2 by Cockcroft-Gault: (140- age) × (weight in&#xD;
               kg) × (0.85 if female) 72 × (serum creatinine in mg/dL)&#xD;
  &#xD;
            -  International normalized ratio (INR) and activated partial thromboplastin time (aPTT)&#xD;
               =&lt; 1.5 × ULN (This applies only to patients who do not receive therapeutic&#xD;
               anticoagulation; patients receiving therapeutic anticoagulation, such as&#xD;
               low-molecular-weight heparin or warfarin, should be on a stable dose.)&#xD;
  &#xD;
            -  Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral&#xD;
               therapy with undetectable viral load within 6 months are eligible for this trial&#xD;
  &#xD;
            -  For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral&#xD;
               load must be undetectable on suppressive therapy, if indicated&#xD;
  &#xD;
                 -  Patients with a history of hepatitis C virus (HCV) infection must have been&#xD;
                    treated and cured. For patients with HCV infection who are currently on&#xD;
                    treatment, they are eligible if they have an undetectable HCV viral load&#xD;
  &#xD;
            -  Patients with treated brain metastases are eligible if follow-up brain imaging 6-8&#xD;
               weeks after central nervous system (CNS)-directed therapy shows no evidence of&#xD;
               progression or CNS lymphoma&#xD;
  &#xD;
            -  Patients with a prior or concurrent malignancy whose natural history or treatment does&#xD;
               not have the potential to interfere with the safety or efficacy assessment of the&#xD;
               investigational regimen are eligible for this trial&#xD;
  &#xD;
            -  For women of childbearing potential: agreement to remain abstinent (refrain from&#xD;
               heterosexual intercourse) or use contraceptive measures, and agreement to refrain from&#xD;
               donating eggs, as defined below:&#xD;
  &#xD;
                 -  Women must remain abstinent or use contraceptive methods with a failure rate of&#xD;
                    1% per year during the treatment period and for 3 months after the final dose of&#xD;
                    mosunetuzumab, 3 months after the final dose of polatuzumab vedotin, and 1 month&#xD;
                    after the last dose of lenalidomide&#xD;
  &#xD;
                 -  For men: agreement to remain abstinent (refrain from heterosexual intercourse) or&#xD;
                    use a condom, and agreement to refrain from donating sperm, as defined below:&#xD;
  &#xD;
                 -  With female partners of childbearing potential, men must remain abstinent or use&#xD;
                    a condom during the treatment period, 5 months after the final dose of&#xD;
                    polatuzumab vedotin, and 1 month after the last dose of lenalidomide&#xD;
  &#xD;
            -  Some concurrent cancer therapeutics (e.g., prostate, breast hormonal-based therapy)&#xD;
               are allowed&#xD;
  &#xD;
            -  Ability to understand and the willingness to sign a written informed consent document.&#xD;
               Legally authorized representatives may sign and give informed consent on behalf of&#xD;
               study participants&#xD;
  &#xD;
            -  Agree to comply with all local requirements of the lenalidomide risk minimization plan&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Plasmablastic lymphoma, primary mediastinal B-cell lymphoma, gray zone lymphoma&#xD;
  &#xD;
            -  Patients who have not recovered from adverse events due to prior anti-cancer therapy&#xD;
               (i.e., have residual toxicities &gt; grade 1) with the exception of alopecia&#xD;
  &#xD;
            -  Patients who are receiving any other investigational agents or treatments&#xD;
  &#xD;
            -  Any condition, including the presence of laboratory abnormalities, which places the&#xD;
               subject at unacceptable risk if he/she were to participate in the study or confounds&#xD;
               the ability to interpret data from the study&#xD;
  &#xD;
            -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
               composition to mosunetuzumab or other agents used in study&#xD;
  &#xD;
            -  Patients with uncontrolled intercurrent illness&#xD;
  &#xD;
            -  Uncontrolled or known active bacterial, viral, fungal, mycobacterial, parasitic, or&#xD;
               other infection (defined as ongoing signs/symptoms related to the infection without&#xD;
               improvement despite appropriate antibiotics, antiviral therapy and/or other treatment)&#xD;
               at study enrollment, or any major episode of infection requiring treatment with IV&#xD;
               antibiotics or hospitalization (relating to the completion of the course of&#xD;
               antibiotics) within 4 weeks prior to first study treatment administration&#xD;
  &#xD;
            -  Active CNS involvement or detectable disease by lymphoma, including leptomeningeal&#xD;
               involvement&#xD;
  &#xD;
            -  Pregnant women are excluded from this study because mosunetuzumab is bispecific&#xD;
               antibody with the potential for teratogenic or abortifacient effects. Because there is&#xD;
               an unknown but potential risk for adverse events in nursing infants secondary to&#xD;
               treatment of the mother with mosunetuzumab, breastfeeding should be discontinued if&#xD;
               the mother is treated with mosunetuzumab. These potential risks may also apply to&#xD;
               other agents used in this study. Pregnant or breastfeeding, or intending to become&#xD;
               pregnant during the study or within 3 months after the final dose of mosunetuzumab, 3&#xD;
               months after the final dose of polatuzumab vedotin, and 1 month after the final dose&#xD;
               of lenalidomide&#xD;
  &#xD;
            -  Patients with known history or current symptoms of cardiac disease, or history of&#xD;
               treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac&#xD;
               function using the New York Heart Association Functional Classification. To be&#xD;
               eligible for this trial, patients should be class 2B or better&#xD;
  &#xD;
            -  Known or suspected chronic active Epstein-Barr virus (EBV) infection&#xD;
  &#xD;
            -  Patients with any other significant condition(s) that would make this protocol&#xD;
               unreasonably hazardous&#xD;
  &#xD;
                 -  Current &gt; grade 1 peripheral neuropathy&#xD;
  &#xD;
                 -  Prior solid organ transplantation&#xD;
  &#xD;
                 -  Patients with known or suspected history of hemophagocytic lymphohistiocytosis&#xD;
                    (HLH)&#xD;
  &#xD;
                 -  Patients with history of confirmed progressive multifocal leukoencephalopathy&#xD;
                    (PML)&#xD;
  &#xD;
                 -  Currently active or uncontrolled autoimmune disease&#xD;
  &#xD;
                      -  Patients with a history of autoimmune-related hypothyroidism on a stable&#xD;
                         dose of thyroid replacement hormone may be eligible&#xD;
  &#xD;
                      -  Patients with controlled type 1 diabetes mellitus who are on an insulin&#xD;
                         regimen are eligible for the study&#xD;
  &#xD;
                      -  Patients with a history of disease-related immune thrombocytopenic purpura,&#xD;
                         autoimmune hemolytic anemia, or other stable autoimmune diseases may be&#xD;
                         eligible&#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>Joseph M Tuscano</last_name>
      <role>Principal Investigator</role>
      <affiliation>City of Hope Comprehensive Cancer Center LAO</affiliation>
    </overall_official>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 26, 2023</study_first_submitted>
    <study_first_submitted_qc>August 26, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 29, 2023</study_first_posted>
    <last_update_submitted>September 5, 2023</last_update_submitted>
    <last_update_submitted_qc>September 5, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 6, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Lymphoma</mesh_term>
      <mesh_term>Lymphoma, B-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>Lenalidomide</mesh_term>
      <mesh_term>Antibodies</mesh_term>
      <mesh_term>Immunoglobulins</mesh_term>
      <mesh_term>Antibodies, Monoclonal</mesh_term>
      <mesh_term>Antibodies, Bispecific</mesh_term>
      <mesh_term>Immunoconjugates</mesh_term>
      <mesh_term>Polatuzumab vedotin</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.</ipd_description>
      <ipd_url>https://grants.nih.gov/policy/sharing.htm</ipd_url>
    </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/NCT06015880
  org study id: NCI-2023-06477
  secondary id: NCI-2023-06477
  secondary id: PHI-141
  secondary id: 10601
  secondary id: 10601
  secondary id: UM1CA186717
  nct id: NCT06015880
  lead sponsor: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: No
  This phase I trial studies the side effects and best dose of mosunetuzumab when given
        together with polatuzumab vedotin and lenalidomide in treating patients with diffuse large
        B-cell lymphoma (DLBCL) that has come back after a period of improvement (relapsed) or that
        has not responded to previous treatment (refractory). Mosunetuzumab and polatuzumab vedotin
        are monoclonal antibodies that may interfere with the ability of cancer cells to grow and
        spread. Polatuzumab, linked to a toxic agent called vedotin, attaches to CD79B positive
        cancer cells in a targeted way and delivers vedotin to kill them. Lenalidomide may stimulate
        or suppress the immune system in different ways and stop cancer cells from growing and by
        preventing the growth of new blood vessels that cancer cells need to grow. Giving
        mosunetuzumab with polatuzumab vedotin and lenalidomide may work better in treating patients
        with relapsed/refractory DLBCL.
  PRIMARY OBJECTIVE:
  
        I. To determine the safety and tolerability of mosunetuzumab + polatuzumab vedotin +
        lenalidomide in relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL).
  
        SECONDARY OBJECTIVE:
  
        I. To observe and record anti-tumor activity of the combination of mosunetuzumab, polatuzumab
        vedotin, and lenalidomide in R/R DLBCL.
  
        EXPLORATORY OBJECTIVES:
  
        I. To assess the efficacy in patients that have failed prior polatuzumab vedotin containing
        regimens (i.e., patients who progressed/relapsed after prior polatuzumab).
  
        II. To assess anti-tumor activity in patients that a) have < complete response (CR) or
        Deauville score of 3 or worse at day 90 (D90) (or before) after standard of care chimeric
        antigen receptor (CAR) T-cell therapy; b) other patients who have failed prior treatment
        (e.g. relapse after day 90 from CAR-T, or relapsed after other therapies and were not
        considered candidates for CAR-T).
  
        III. To identify biomarkers that can predict the response to mosunetuzumab + polatuzumab
        vedotin + lenalidomide.
  
        IV. To describe anti-tumor activity in patients whose tumors have previously failed to
        respond to polatuzumab (i.e., patients who progressed/relapsed after prior polatuzumab).
  
        OUTLINE: This is a dose-escalation study of mosunetuzumab, followed by a dose-expansion
        study.
  
        Patients receive mosunetuzumab intravenously (IV) over 2-4 hours on days 1, 8, and 15 of
        cycle 1 and then day 1 of each subsequent cycle. Treatment repeats every 28 days for 8 cycles
        in patients who achieve a complete response (CR) or up to 17 cycles for patients with a
        partial response (PR) or stable disease (SD) in the absence of disease progression or
        unacceptable toxicity. Patients also recieve polatuzumab vedotin IV over 30-90 minutes on day
        1 for 6 cycles and lenalidomide orally (PO) on days 1-21 for 8 cycles in patients who achieve
        CR or up to 17 cycles. Cycles repeat every 28 days in the absence of disease progression or
        unacceptable toxicity. Patients undergo positron emission tomography (PET)/ computed
        tomography (CT) and blood sample collection throughout the study.
  
        After completion of study treatment, patients are followed up for 2 years.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Safety and tolerability of monsunetuzumab+polatuzumab vedotin+lenalidomide for determination of recommended phase 2 dose
  time frame: During cycle 1 (cycle=28 days)
  description: Dose limiting toxicity will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
  measure: Objective response rate
  time frame: Up to 2 years
  description: Will be assessed per the Lugano 2014 criteria.
  measure: Complete response rate
  time frame: Up to 2 years
  description: Will be assessed per the Lugano 2014 criteria.
  measure: Progression free survival
  time frame: Up to 2 years
  description: Will be assessed per the Lugano 2014 criteria.
  measure: Duration of response
  time frame: From time of initial response assessment demonstrating at least partial response until disease response assessment that demonstrates progressive disease, assessed up to 2 years
  description: Will be assessed per the Lugano 2014 criteria.
  measure: CD79b expression levels
  time frame: At baseline
  description: Will be assessed via ribonucleic acid and immunohistochemistry assessment and correlation with response.
  measure: Frequency of CD4 T-cells and IFN-gamma+ producing CD4 T-cells
  time frame: At baseline and up to 2 years
  description: Will be assessed via intracellular flow cytometry.
  measure: Ultrasensitive determination of cytokine profile
  time frame: At baseline and up to 2 years
  description: Will be assessed with Luminex assay to identify biomarkers that might predict a response.
  measure: Efficacy in relapsed/refractory double-expresser lymphoma and double-hit lymphoma
  time frame: Up to 2 years
  measure: Efficacy post chimeric antigen receptor (CAR) T-cell therapy
  time frame: Up to 2 years
  measure: Efficacy post polatuzumab vedotin
  time frame: Up to 2 years
  measure: Percent of patients able to start the triplet therapy
  time frame: At cycle 2 (cycle=28 days)
  measure: CAR T-cell expansion and persistence
  time frame: Up to 2 years
  measure: CAR T-cell immunophenotypes
  time frame: Up to 2 years
  arm group label: Treatment (mosunetuzumab, polatuzumab vedotin, lenalidomide)
  arm group type: Experimental
  description: Patients receive mosunetuzumab IV over 2-4 hours on days 1, 8, and 15 of cycle 1 and then day 1 of each subsequent cycle. Treatment repeats every 28 days for 8 cycles in patients who achieve a CR or up to 17 cycles for patients with a PR or SD in the absence of disease progression or unacceptable toxicity. Patients also recieve polatuzumab vedotin IV over 30-90 minutes on day 1 for 6 cycles and lenalidomide PO on days 1-21 for 8 cycles in patients who achieve CR or up to 17 cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo PET/CT and blood sample collection throughout the study.
  intervention type: Procedure
  intervention name: Biospecimen Collection
  description: Undergo blood sample collection
  arm group label: Treatment (mosunetuzumab, polatuzumab vedotin, lenalidomide)
  other name: Biological Sample Collection
  other name: Biospecimen Collected
  other name: Specimen Collection
  intervention type: Procedure
  intervention name: Computed Tomography
  description: Undergo PET/CT
  arm group label: Treatment (mosunetuzumab, polatuzumab vedotin, lenalidomide)
  other name: CAT
  other name: CAT Scan
  other name: Computed Axial Tomography
  other name: Computerized Axial Tomography
  other name: Computerized axial tomography (procedure)
  other name: Computerized Tomography
  other name: CT
  other name: CT Scan
  other name: tomography
  intervention type: Drug
  intervention name: Lenalidomide
  description: Given PO
  arm group label: Treatment (mosunetuzumab, polatuzumab vedotin, lenalidomide)
  other name: CC-5013
  other name: CC5013
  other name: CDC 501
  other name: Revlimid
  intervention type: Biological
  intervention name: Mosunetuzumab
  description: Given IV
  arm group label: Treatment (mosunetuzumab, polatuzumab vedotin, lenalidomide)
  other name: Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody BTCT4465A
  other name: BTCT 4465A
  other name: BTCT-4465A
  other name: BTCT4465A
  other name: CD20/CD3 BiMAb BTCT4465A
  other name: Lunsumio
  other name: Mosunetuzumab-axgb
  other name: RG 7828
  other name: RG-7828
  other name: RG7828
  other name: RO7030816
  intervention type: Drug
  intervention name: Polatuzumab Vedotin
  description: Given IV
  arm group label: Treatment (mosunetuzumab, polatuzumab vedotin, lenalidomide)
  other name: ADC DCDS4501A
  other name: Antibody-Drug Conjugate DCDS4501A
  other name: DCDS4501A
  other name: FCU 2711
  other name: polatuzumab vedotin-piiq
  other name: Polivy
  other name: RG7596
  other name: Ro 5541077-000
  intervention type: Procedure
  intervention name: Positron Emission Tomography
  description: Undergo PET/CT
  arm group label: Treatment (mosunetuzumab, polatuzumab vedotin, lenalidomide)
  other name: Medical Imaging, Positron Emission Tomography
  other name: PET
  other name: PET Scan
  other name: Positron emission tomography (procedure)
  other name: Positron Emission Tomography Scan
  other name: Positron-Emission Tomography
  other name: proton magnetic resonance spectroscopic imaging
  other name: PT
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Joseph M Tuscano
  role: Principal Investigator
  affiliation: City of Hope Comprehensive Cancer Center LAO
  responsible party type: Sponsor
  mesh term: Lymphoma
  mesh term: Lymphoma, B-Cell
  mesh term: Lymphoma, Large B-Cell, Diffuse
  mesh term: Lenalidomide
  mesh term: Antibodies
  mesh term: Immunoglobulins
  mesh term: Antibodies, Monoclonal
  mesh term: Antibodies, Bispecific
  mesh term: Immunoconjugates
  mesh term: Polatuzumab vedotin
  sharing ipd: Yes
  ipd description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
  ipd url: https://grants.nih.gov/policy/sharing.htm