<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/NCT04416451</url>
  </required_header>
  <id_info>
    <org_study_id>20-115</org_study_id>
    <nct_id>NCT04416451</nct_id>
  </id_info>
  <brief_title>A Phase II Study Using Rituximab Plus Venetoclax in the Front Line Treatment of Marginal Zone Lymphoma</brief_title>
  <official_title>A Phase II Study Using Rituximab Plus Venetoclax in the Front Line Treatment of Marginal Zone Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Memorial Sloan Kettering Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AbbVie</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Memorial Sloan Kettering Cancer Center</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will help researchers understand how effective the combination of venetoclax and&#xD;
      rituximab is in treating MZL in people who have not received a previous treatment for their&#xD;
      cancer.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">May 4, 2021</start_date>
  <completion_date type="Anticipated">June 2024</completion_date>
  <primary_completion_date type="Anticipated">June 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>This is a single-arm, phase II study.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>complete response rate (CRR)</measure>
    <time_frame>2 years</time_frame>
    <description>Will be evaluated in this study using the RECIL criteria.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>overall response rates (ORR)</measure>
    <time_frame>2 years</time_frame>
    <description>Overall response rate (ORR) will be measured as the number of patients that achieve a PR or CR per RECIL criteria.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Marginal Zone Lymphoma</condition>
  <arm_group>
    <arm_group_label>Rituximab and Venetoclax</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be treated with an Induction phase of rituximab 375 mg/m2 weekly for 4 weeks. Patients will undergo restaging imaging after the last of 4 weekly rituximab doses and before beginning venetoclax. Based on post-rituximab restaging studies, patients will be risk-stratified for risk of Tumor Lysis Syndrome (TLS) and treated in the appropriate setting with TLS prophylaxis per institutional TLS guide lines starting at week 5. Oral venetoclax will follow a ramp-up dosing schedule and will be taken daily after 4 weeks of rituximab therapy. Following the 4-week ramped-up phase of venetoclax, patients will begin their target dose of venetoclax and continue for a maximum of 24 months. In addition, patients will receive rituximab 375 mg/m2 starting on day 1 of the maintenance phase and repeated once every 3 months for 12 months. Venetoclax may be continued after this period if patient has not achieved a complete remission</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rituximab</intervention_name>
    <description>Induction:Rituximab will be administered per institutional guidelines once per week for 4 weeks at a dose of 375 mg/m^2. Maintenance: In addition, patients will receive rituximab 375 mg/m2 starting on day 1 of the maintenance phase and repeated once every 3 months for 12 months (for a total of 4 infusions). On days when venetoclax and rituximab will both be administered, patients will take venetoclax prior to administration of rituximab.</description>
    <arm_group_label>Rituximab and Venetoclax</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Venetoclax</intervention_name>
    <description>Induction: Starting one week after the last induction dose of rituximab (approximately week 5), venetoclax will be administered orally at a flat dose of 100 mg daily and escalating each week to a target dose of 800 mg daily on the following schedule:&#xD;
Week 1: 100 mg&#xD;
Week 2: 200 mg&#xD;
Week 3: 400 mg&#xD;
Week 4: 800 mg Maintenance: Following the 4-week induction phase ramp-up of venetoclax, patients will begin their target dose of 800 mg venetoclax daily and continue this dose during the 24- month maintenance treatment phase. On days when venetoclax and rituximab will both be administered, patients will take venetoclax prior to administration of rituximab.</description>
    <arm_group_label>Rituximab and Venetoclax</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age greater than or equal to 18 years&#xD;
&#xD;
          -  Histologically confirmed Marginal Zone Lymphoma&#xD;
&#xD;
          -  Patients must have measurable disease as defined by at least one lymph node ≥1.5 cm or&#xD;
             spleen &gt;13 cm.&#xD;
&#xD;
             °Patients with intestinal MALT lymphoma must have disease that is detectable by EGD or&#xD;
             colonoscopy with biopsy&#xD;
&#xD;
          -  Patients with gastric MALT lymphoma must be h. pylori negative&#xD;
&#xD;
             °Patients who are h. pylori positive are allowed if they have failed a trial of&#xD;
             h.pylori eradication&#xD;
&#xD;
          -  Patients with gastric MALT lymphoma who are h. pylori negative or who have&#xD;
             relapsed/refractory disease after h. pylori eradication must be ineligible for, have&#xD;
             refused or failed gastric radiation therapy&#xD;
&#xD;
          -  ECOG performance status ≤ 1&#xD;
&#xD;
          -  Life expectancy of greater than 2 years&#xD;
&#xD;
          -  Patients must have normal organ function as defined below:&#xD;
&#xD;
               -  Platelet count ≥ 50,000 cells/mm^3&#xD;
&#xD;
               -  Hemoglobin ≥ 8.0 g/dL&#xD;
&#xD;
               -  Absolute neutrophil count ≥ 1000 cells/mcL. If there is documented bone marrow&#xD;
                  involvement, ANC must be &gt;/= 500 cells/mcL&#xD;
&#xD;
               -  Total bilirubin &lt; 1.5 x upper normal institutional limits. In patients with&#xD;
                  Gilbert's disease or documented liver involvement, total bilirubin up to 3x ULN&#xD;
                  will be allowed&#xD;
&#xD;
               -  AST(SGOT)/ALT(SGPT) &lt;3 x institutional upper limit of normal unless elevation is&#xD;
                  caused by liver involvement with MZL&#xD;
&#xD;
          -  AST(SGOT)/ALT(SGPT) &lt;3 x institutional upper limit of normal unless elevation is&#xD;
             caused by liver involvement with MZL&#xD;
&#xD;
             °OR Creatinine clearance &gt;60 mL/min for patients with creatinine levels above&#xD;
             institutional normal (by Cockcroft-Gault estimate or 12-24h creatinine clearance&#xD;
             measurements).&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document.&#xD;
&#xD;
          -  Able to swallow pills&#xD;
&#xD;
          -  HIV-positive patients on combination antiretroviral therapy are eligible if their HIV&#xD;
             is under adequate control with an antiretroviral regimen that has been stable for &gt; 4&#xD;
             weeks, as long as the CD4 count is &gt; 300. Appropriate studies will be undertaken in&#xD;
             patients receiving combination antiretroviral therapy when indicated.&#xD;
&#xD;
          -  Patients with Hepatitis B surface antibody serum positivity due to prior immunization,&#xD;
             as well as those with Hepatitis B core antibody positivity with negative PCR on&#xD;
             antiviral therapy will be eligible.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have had prior systemic therapy, including rituximab&#xD;
&#xD;
          -  Patients who have had prior radiation therapy, with the following exception:&#xD;
&#xD;
             °Palliative radiotherapy RT is allowed but must be completed at least 1 week prior to&#xD;
             treatment on this study, and prior baseline imaging studies or biopsies. Patients must&#xD;
             meet criteria for measurable/assessable disease as outlined above after completion of&#xD;
             RT&#xD;
&#xD;
          -  Prior treatment with ibrutinib or other BTK inhibitor&#xD;
&#xD;
          -  Patients with h. pylori-associated gastric MALT or stage I/II MZL will be excluded&#xD;
             unless they are deemed to be unfit for radiation therapy with curative intent.&#xD;
&#xD;
          -  Patients with uncontrolled intercurrent illness including, but not limited to, ongoing&#xD;
             or active infection, symptomatic congestive heart failure, unstable angina pectoris,&#xD;
             cardiac arrhythmia, or psychiatric illness/social situations that would limit&#xD;
             compliance with study requirements&#xD;
&#xD;
             °Patients with Hep B core ab positivity are allowed provided Hep B PCR is undetectable&#xD;
&#xD;
          -  Lactating or pregnant women&#xD;
&#xD;
          -  Participants unwilling to adhere to institutional guidelines for highly effective&#xD;
             contraception for 12 months after the last dose of rituximab&#xD;
&#xD;
          -  Patients who received moderate or strong CYP3A inhibitors (such as fluconazole,&#xD;
             ketoconazole, and clarithromycin) within 7 days prior to the first dose of venetoclax.&#xD;
&#xD;
          -  Patients who received moderate or strong CYP3A inducers (such as rifampin,&#xD;
             carbamazepine, phenytoin, St. John's Wort) within 7 days prior to the first dose of&#xD;
             venetoclax.&#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>Andrew Zelenetz, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Memorial Sloan Kettering Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>City of Hope Cancer Center (Data collection only)</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Basking Ridge (All Protocol Activities)</name>
      <address>
        <city>Basking Ridge</city>
        <state>New Jersey</state>
        <zip>07920</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Monmouth (All protocol activities)</name>
      <address>
        <city>Middletown</city>
        <state>New Jersey</state>
        <zip>07748</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Bergen (All protocol Activities)</name>
      <address>
        <city>Montvale</city>
        <state>New Jersey</state>
        <zip>07645</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Commack (All Protocol Activities)</name>
      <address>
        <city>Commack</city>
        <state>New York</state>
        <zip>11725</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Westchester (All Protocol Activities)</name>
      <address>
        <city>Harrison</city>
        <state>New York</state>
        <zip>10604</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center (All Protocol Activities)</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Rockville Centre (All Protocol Activities)</name>
      <address>
        <city>Rockville Centre</city>
        <state>New York</state>
        <zip>11570</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mskcc.org/mskcc/html/44.cfm</url>
    <description>Memorial Sloan Kettering Cancer Center</description>
  </link>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>June 2, 2020</study_first_submitted>
  <study_first_submitted_qc>June 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>June 30, 2023</last_update_submitted>
  <last_update_submitted_qc>June 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Rituximab</keyword>
  <keyword>Venetoclax</keyword>
  <keyword>20-115</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, B-Cell, Marginal Zone</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rituximab</mesh_term>
    <mesh_term>Venetoclax</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.</ipd_description>
  </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/NCT04416451
org study id: 20-115
nct id: NCT04416451
lead sponsor: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
This study will help researchers understand how effective the combination of venetoclax and
      rituximab is in treating MZL in people who have not received a previous treatment for their
      cancer.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: This is a single-arm, phase II study.
primary purpose: Treatment
masking: None (Open Label)
measure: complete response rate (CRR)
time frame: 2 years
description: Will be evaluated in this study using the RECIL criteria.
measure: overall response rates (ORR)
time frame: 2 years
description: Overall response rate (ORR) will be measured as the number of patients that achieve a PR or CR per RECIL criteria.
arm group label: Rituximab and Venetoclax
arm group type: Experimental
description: Patients will be treated with an Induction phase of rituximab 375 mg/m2 weekly for 4 weeks. Patients will undergo restaging imaging after the last of 4 weekly rituximab doses and before beginning venetoclax. Based on post-rituximab restaging studies, patients will be risk-stratified for risk of Tumor Lysis Syndrome (TLS) and treated in the appropriate setting with TLS prophylaxis per institutional TLS guide lines starting at week 5. Oral venetoclax will follow a ramp-up dosing schedule and will be taken daily after 4 weeks of rituximab therapy. Following the 4-week ramped-up phase of venetoclax, patients will begin their target dose of venetoclax and continue for a maximum of 24 months. In addition, patients will receive rituximab 375 mg/m2 starting on day 1 of the maintenance phase and repeated once every 3 months for 12 months. Venetoclax may be continued after this period if patient has not achieved a complete remission
intervention type: Drug
intervention name: Rituximab
description: Induction:Rituximab will be administered per institutional guidelines once per week for 4 weeks at a dose of 375 mg/m^2. Maintenance: In addition, patients will receive rituximab 375 mg/m2 starting on day 1 of the maintenance phase and repeated once every 3 months for 12 months (for a total of 4 infusions). On days when venetoclax and rituximab will both be administered, patients will take venetoclax prior to administration of rituximab.
arm group label: Rituximab and Venetoclax
intervention type: Drug
intervention name: Venetoclax
description: Induction: Starting one week after the last induction dose of rituximab (approximately week 5), venetoclax will be administered orally at a flat dose of 100 mg daily and escalating each week to a target dose of 800 mg daily on the following schedule:
Week 1: 100 mg
Week 2: 200 mg
Week 3: 400 mg
Week 4: 800 mg Maintenance: Following the 4-week induction phase ramp-up of venetoclax, patients will begin their target dose of 800 mg venetoclax daily and continue this dose during the 24- month maintenance treatment phase. On days when venetoclax and rituximab will both be administered, patients will take venetoclax prior to administration of rituximab.
arm group label: Rituximab and Venetoclax
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Andrew Zelenetz, MD, PhD
role: Principal Investigator
affiliation: Memorial Sloan Kettering Cancer Center
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: http://www.mskcc.org/mskcc/html/44.cfm
description: Memorial Sloan Kettering Cancer Center
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, B-Cell, Marginal Zone
mesh term: Rituximab
mesh term: Venetoclax
sharing ipd: Yes
ipd description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.