<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/NCT03036904</url>
  </required_header>
  <id_info>
    <org_study_id>1607017413</org_study_id>
    <nct_id>NCT03036904</nct_id>
  </id_info>
  <brief_title>Study of Venetoclax Plus DA-EPOCH-R for the Treatment of Aggressive B-Cell Lymphomas</brief_title>
  <acronym>V+DA-EPOCH-R</acronym>
  <official_title>Phase I Study of Venetoclax Plus DA-EPOCH-R for the Treatment of Aggressive B-Cell Lymphomas</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Weill Medical College of Cornell University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Genentech, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Weill Medical College of Cornell University</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, open label, single-arm, multi-center, dose-finding study of venetoclax in&#xD;
      combination with DA-EPOCH-R in patients with aggressive B-Cell Lymphomas.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This clinical trial is for men and women with aggressive B-Cell Lymphomas which includes:&#xD;
&#xD;
        -  Diffuse large B-cell lymphoma (DLBCL),&#xD;
&#xD;
        -  B-cell lymphoma unclassifiable with intermediate features between DLBCL and Burkitt&#xD;
           Lymphoma (BL),&#xD;
&#xD;
        -  High grade B-cell lymphoma (HGBCL),&#xD;
&#xD;
        -  Transformed indolent NHL (TiNHL). The aggressive B-cell lymphomas enrolling on this&#xD;
           study have been recognized to have a poor prognosis with the use of conventional&#xD;
           chemoimmunotherapy. DA-EPOCH-R is an alternative highly effective chemoimmunotherapy&#xD;
           platform for these lymphomas and may serve as an optimal chemotherapy backbone for the&#xD;
           incorporation of novel agents such as venetoclax.&#xD;
&#xD;
      The Bcl-2 protein plays a significant role in the regulation of cell death in malignant&#xD;
      cells. Overexpression of Bcl-2 family proteins is associated with chemo-resistance of a broad&#xD;
      variety of cancers, and BCL2 abnormalities are common in aggressive B-cell Lymphomas.&#xD;
      Venetoclax is a highly selective Bcl-2 family protein inhibitor that binds to Bcl-2 family&#xD;
      proteins to potentially overcome resistance and enhance responses to therapy. This study has&#xD;
      been designed to evaluate the safety and preliminary efficacy of venetoclax in combination&#xD;
      with DA-EPOCH-R.&#xD;
&#xD;
      Subjects will receive venetoclax in conjunction with six 21-day cycles of DA-EPOCH-R. Dosing&#xD;
      for DA-EPOCH-R will follow established protocols. Venetoclax will be administered on days 3&#xD;
      through 12 during cycle 1 and days 1 through 10 of each subsequent cycle. Following&#xD;
      completion of therapy, subjects will be followed every three months for up to two years.&#xD;
      Subjects removed from study due to toxicity will be followed until resolution or&#xD;
      stabilization of the toxicity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 6, 2017</start_date>
  <completion_date type="Actual">November 11, 2021</completion_date>
  <primary_completion_date type="Actual">November 11, 2021</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>Determination of the maximal tolerated dose (MTD)</measure>
    <time_frame>Approximately 24 months</time_frame>
    <description>Determination of the maximal tolerated dose (MTD)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Determination of dose limiting toxicity (DLT)</measure>
    <time_frame>Approximately 24 months</time_frame>
    <description>Determination of dose limiting toxicity (DLT)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Define incidence and severity of adverse events, defined according to CTCAE v 4.0.</measure>
    <time_frame>Approximately 24 months</time_frame>
    <description>Define incidence and severity of adverse events, defined according to CTCAE v 4.0.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall response rate</measure>
    <time_frame>Approximately 24 months</time_frame>
    <description>Overall response rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complete response rate</measure>
    <time_frame>Approximately 24 months</time_frame>
    <description>Complete response rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Event-free survival</measure>
    <time_frame>Approximately 24 months</time_frame>
    <description>Event-free survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>Approximately 24 months</time_frame>
    <description>Progression Free Survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Approximately 24 months</time_frame>
    <description>Overall survival</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Diffuse Large B-Cell Lymphoma</condition>
  <condition>High Grade B-Cell Lymphoma</condition>
  <arm_group>
    <arm_group_label>Venetoclax plus DA-EPOCH-R</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Venetoclax will be given in conjunction with 6 cycles of DA-EPOCH-R (doxorubicin hydrochloride, etoposide, vincristine sulfate, cyclophosphamide, prednisone, rituximab). The dosing schedule and regimen for DA-EPOCH-R will follow established protocols. Venetoclax will be administered days 1-10 of each 21-day cycle, with the exception of cycle 1, during which venetoclax dose will commence on day 3 and continue through day 12, so as to clarify attribution of any observed TLS and/or infusion reactions, and minimize tumor lysis syndrome (TLS) risk.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Venetoclax</intervention_name>
    <description>Venetoclax will be administered orally on days 3-12 in cycle 1, and days 1-10 with all subsequent cycles except dose level -1. If dose level -1 is required, venetoclax will be administered on days 3-7 in cycle 1 and 1-5 with subsequent cycles.</description>
    <arm_group_label>Venetoclax plus DA-EPOCH-R</arm_group_label>
    <other_name>Venclexta</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rituximab</intervention_name>
    <description>Rituximab will be administered as an IV infusion at 375 mg/m2 on day 1 of each cycle of DA-EPOCH-R, immediately prior to the start of chemotherapy. Oral pre-medication 650 mg of acetaminophen and 50-100 mg diphenhydramine hydrochloride will be administered 30 to 60 minutes prior to starting each infusion of rituximab. The first rituximab infusion should be started at 50 mg/hr, and increased in 50-mg/hr increments every 30 minutes to a maximum rate of 400 mg/hr. If this rate of escalation is well tolerated the second and subsequent infusions can begin at a rate of 100 mg/hr and increase in 100 mg/hr increments every 30 minutes to a maximum of 400 mg/hr. CAUTION: DO NOT ADMINISTER AS AN INTRAVENOUS PUSH OR BOLUS.</description>
    <arm_group_label>Venetoclax plus DA-EPOCH-R</arm_group_label>
    <other_name>Rituxan</other_name>
    <other_name>IDEC-C2B8</other_name>
    <other_name>chimeric anti-CD20 monoclonal antibody</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Etoposide</intervention_name>
    <description>Etoposide will be obtained from commercial supply, and will be given for a total of 6 cycles for all patients. The drug will be given by IV route.</description>
    <arm_group_label>Venetoclax plus DA-EPOCH-R</arm_group_label>
    <other_name>VP-16</other_name>
    <other_name>VePesid</other_name>
    <other_name>etopophos</other_name>
    <other_name>toposar</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vincristine Sulfate</intervention_name>
    <description>Vincristine Sulfate will be obtained from commercial supply, and will be given for a total of 6 cycles for all patients. The drug will be given by IV route.</description>
    <arm_group_label>Venetoclax plus DA-EPOCH-R</arm_group_label>
    <other_name>LCR</other_name>
    <other_name>VCR</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Cyclophosphamide will be obtained from commercial supply, and will be given for a total of 6 cycles for all patients. The drug will be given by IV route.</description>
    <arm_group_label>Venetoclax plus DA-EPOCH-R</arm_group_label>
    <other_name>cytoxan</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prednisone</intervention_name>
    <description>Prednisone will be obtained from commercial supply, and will be given for a total of 6 cycles for all patients. Prednisone will be given orally.</description>
    <arm_group_label>Venetoclax plus DA-EPOCH-R</arm_group_label>
    <other_name>Deltasone</other_name>
    <other_name>Orasone</other_name>
    <other_name>Paracort</other_name>
    <other_name>Cortan</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doxorubicin Hydrochloride</intervention_name>
    <description>Doxorubicin Hydrochloride will be obtained from commercial supply, and will be given for a total of 6 cycles for all patients. The drug will be given by IV route.</description>
    <arm_group_label>Venetoclax plus DA-EPOCH-R</arm_group_label>
    <other_name>Hydroxydaunomycin Hydrochloride</other_name>
    <other_name>Hydroxydoxorubicin Hydrochloride</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Adults age 18-80 years&#xD;
&#xD;
          -  Histologically confirmed, biopsy-proven diagnosis of DLBCL, BCLu, HGBCL, or TiNHL.&#xD;
&#xD;
        Richter's transformation from Chronic Lymphocytic Leukemia (CLL) is not eligible.&#xD;
&#xD;
          -  Subjects with DLBCL, BCLu, HGBCL NOS, or HGBCL with translocations of MYC and BCL2&#xD;
             and/or BCL6, must have had no prior chemotherapy for lymphoma. Steroids for palliation&#xD;
             prior to enrollment are allowed.&#xD;
&#xD;
          -  Subjects with TiNHL are eligible if they have received no prior cytotoxic chemotherapy&#xD;
             for lymphoma. Steroids, rituximab, and external beam radiation therapy as prior&#xD;
             therapy for indolent lymphoma is allowed.&#xD;
&#xD;
          -  Ann Arbor stage II-IV disease (Stage I primary mediastinal B-cell lymphoma will also&#xD;
             be eligible)&#xD;
&#xD;
          -  Ability to provide signed Informed Consent Form&#xD;
&#xD;
          -  Ability and willingness to comply with the requirements of the study protocol&#xD;
&#xD;
          -  Measureable disease (defined as at least 1.5 cm in diameter).&#xD;
&#xD;
          -  Adequate organ and bone marrow function:&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) at least 1,000/mm3&#xD;
&#xD;
          -  Platelet count at least 100,000/mm3.&#xD;
&#xD;
          -  Total bilirubin at most1.5 x the upper limit of the normal range (ULN), except&#xD;
             Gilbert's disease&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) at most 3 x ULN.&#xD;
&#xD;
          -  Calculated creatinine clearance at least 30 mL/min.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Known hypersensitivity to any of the study drugs&#xD;
&#xD;
          -  History of other malignancy that could affect compliance with the protocol or&#xD;
             interpretation of results&#xD;
&#xD;
          -  Patients with a history of curatively treated basal or squamous cell carcinoma of the&#xD;
             skin or in situ carcinoma of the cervix are generally eligible. Patients with a&#xD;
             malignancy that has been treated, but not with curative intent, will also be excluded,&#xD;
             unless the malignancy has been in remission without treatment for at least 2 years&#xD;
             prior to enrollment.&#xD;
&#xD;
          -  Known CNS involvement at diagnosis&#xD;
&#xD;
          -  Richter's transformation from CLL&#xD;
&#xD;
          -  Evidence of other clinically significant uncontrolled condition(s) including, but not&#xD;
             limited to, uncontrolled systemic infection (viral, bacterial, or fungal)&#xD;
&#xD;
          -  Major surgery within 3 weeks prior to the start of study treatment&#xD;
&#xD;
          -  Infection with human immunodeficiency virus (HIV)&#xD;
&#xD;
          -  Women who are pregnant or lactating&#xD;
&#xD;
          -  Female patients who are not surgically sterile or postmenopausal (for at least 1 year)&#xD;
             must practice at least one of the following methods of birth control throughout the&#xD;
             duration of study participation and for at least 3 months after study treatment:&#xD;
&#xD;
          -  Total abstinence from sexual intercourse&#xD;
&#xD;
          -  A vasectomized partner&#xD;
&#xD;
          -  Hormonal contraceptives (oral, parenteral, vaginal ring, or transdermal) that started&#xD;
             at least 3 months prior to study drug administration&#xD;
&#xD;
          -  Double-barrier method (condom plus diaphragm or cervical cup with spermicidal&#xD;
             contraceptive sponge, jellies, or cream)&#xD;
&#xD;
          -  Non-vasectomized male patients must comply with at least one of the following methods&#xD;
             of birth control throughout the duration of study participation and for at least 3&#xD;
             months after study treatment:&#xD;
&#xD;
          -  A partner who is surgically sterile or postmenopausal (for at least 1 year) or who is&#xD;
             taking hormonal contraceptives (oral, parenteral, vaginal ring, or transdermal) for at&#xD;
             least 3 months prior to study drug administration&#xD;
&#xD;
          -  Total abstinence from sexual intercourse&#xD;
&#xD;
          -  Double-barrier method (condom plus diaphragm or cervical cup with spermicidal,&#xD;
             contraceptive sponge, jellies, or cream)&#xD;
&#xD;
          -  Malabsorption syndrome or other condition that precludes enteral route of&#xD;
             administration&#xD;
&#xD;
          -  Known allergy to both xanthine oxidase inhibitors and rasburicase&#xD;
&#xD;
          -  Subjects with positive HBV core antibody or surface antigen are eligible as long as&#xD;
             they have an undetectable HBV DNA PCR, and receive concurrent antiviral therapy with&#xD;
             entecavir, tenofovir, or lamivudine, and continued for a minimum of 6 months after&#xD;
             completion of therapy.&#xD;
&#xD;
          -  Active hepatitis C (defined as a positive HCV viral load)&#xD;
&#xD;
          -  Chronic use of moderate or strong CYP3A4 modulators (inhibitor or inducer) or any&#xD;
             other prohibited medications. A washout period of 7 days is required prior to&#xD;
             venetoclax dosing if a prohibited medication is discontinued.&#xD;
&#xD;
          -  Chronic use of a P-gp inhibitor, or a P-gp substrate with a narrow therapeutic index.&#xD;
             A washout period of 7 days is required prior to venetoclax dosing if a prohibited&#xD;
             medication is discontinued.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John P. Leonard, M.D.</last_name>
    <role>Study Chair</role>
    <affiliation>Weill Medical College of Cornell University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jeremy S. Abramson, M.D.</last_name>
    <role>Study Chair</role>
    <affiliation>Massachusetts General Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Sarah Rutherford, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Weill Medical College of Cornell University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Massachusetts General Hospital Cancer Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02284</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Weill Cornell Medicine</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ohio State University Medical Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fox Chase Cancer Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>January 27, 2017</study_first_submitted>
  <study_first_submitted_qc>January 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 30, 2017</study_first_posted>
  <last_update_submitted>August 23, 2022</last_update_submitted>
  <last_update_submitted_qc>August 23, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 24, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>venetoclax</keyword>
  <keyword>dose-adjusted EPOCH-R</keyword>
  <keyword>aggressive B-Cell lymphoma</keyword>
  <keyword>Lymphoma</keyword>
  <keyword>Non-Hodgkin lymphoma</keyword>
  <keyword>Diffuse large B-cell lymphoma</keyword>
  <keyword>Double hit lymphoma</keyword>
  <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>
    <mesh_term>Aggression</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prednisone</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Rituximab</mesh_term>
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Liposomal doxorubicin</mesh_term>
    <mesh_term>Etoposide</mesh_term>
    <mesh_term>Vincristine</mesh_term>
    <mesh_term>Venetoclax</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/NCT03036904
org study id: 1607017413
nct id: NCT03036904
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a phase I, open label, single-arm, multi-center, dose-finding study of venetoclax in
      combination with DA-EPOCH-R in patients with aggressive B-Cell Lymphomas.
This clinical trial is for men and women with aggressive B-Cell Lymphomas which includes:

        -  Diffuse large B-cell lymphoma (DLBCL),

        -  B-cell lymphoma unclassifiable with intermediate features between DLBCL and Burkitt
           Lymphoma (BL),

        -  High grade B-cell lymphoma (HGBCL),

        -  Transformed indolent NHL (TiNHL). The aggressive B-cell lymphomas enrolling on this
           study have been recognized to have a poor prognosis with the use of conventional
           chemoimmunotherapy. DA-EPOCH-R is an alternative highly effective chemoimmunotherapy
           platform for these lymphomas and may serve as an optimal chemotherapy backbone for the
           incorporation of novel agents such as venetoclax.

      The Bcl-2 protein plays a significant role in the regulation of cell death in malignant
      cells. Overexpression of Bcl-2 family proteins is associated with chemo-resistance of a broad
      variety of cancers, and BCL2 abnormalities are common in aggressive B-cell Lymphomas.
      Venetoclax is a highly selective Bcl-2 family protein inhibitor that binds to Bcl-2 family
      proteins to potentially overcome resistance and enhance responses to therapy. This study has
      been designed to evaluate the safety and preliminary efficacy of venetoclax in combination
      with DA-EPOCH-R.

      Subjects will receive venetoclax in conjunction with six 21-day cycles of DA-EPOCH-R. Dosing
      for DA-EPOCH-R will follow established protocols. Venetoclax will be administered on days 3
      through 12 during cycle 1 and days 1 through 10 of each subsequent cycle. Following
      completion of therapy, subjects will be followed every three months for up to two years.
      Subjects removed from study due to toxicity will be followed until resolution or
      stabilization of the toxicity.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Determination of the maximal tolerated dose (MTD)
time frame: Approximately 24 months
description: Determination of the maximal tolerated dose (MTD)
measure: Determination of dose limiting toxicity (DLT)
time frame: Approximately 24 months
description: Determination of dose limiting toxicity (DLT)
measure: Define incidence and severity of adverse events, defined according to CTCAE v 4.0.
time frame: Approximately 24 months
description: Define incidence and severity of adverse events, defined according to CTCAE v 4.0.
measure: Overall response rate
time frame: Approximately 24 months
description: Overall response rate
measure: Complete response rate
time frame: Approximately 24 months
description: Complete response rate
measure: Event-free survival
time frame: Approximately 24 months
description: Event-free survival
measure: Progression Free Survival
time frame: Approximately 24 months
description: Progression Free Survival
measure: Overall survival
time frame: Approximately 24 months
description: Overall survival
arm group label: Venetoclax plus DA-EPOCH-R
arm group type: Experimental
description: Venetoclax will be given in conjunction with 6 cycles of DA-EPOCH-R (doxorubicin hydrochloride, etoposide, vincristine sulfate, cyclophosphamide, prednisone, rituximab). The dosing schedule and regimen for DA-EPOCH-R will follow established protocols. Venetoclax will be administered days 1-10 of each 21-day cycle, with the exception of cycle 1, during which venetoclax dose will commence on day 3 and continue through day 12, so as to clarify attribution of any observed TLS and/or infusion reactions, and minimize tumor lysis syndrome (TLS) risk.
intervention type: Drug
intervention name: Venetoclax
description: Venetoclax will be administered orally on days 3-12 in cycle 1, and days 1-10 with all subsequent cycles except dose level -1. If dose level -1 is required, venetoclax will be administered on days 3-7 in cycle 1 and 1-5 with subsequent cycles.
arm group label: Venetoclax plus DA-EPOCH-R
other name: Venclexta
intervention type: Drug
intervention name: Rituximab
description: Rituximab will be administered as an IV infusion at 375 mg/m2 on day 1 of each cycle of DA-EPOCH-R, immediately prior to the start of chemotherapy. Oral pre-medication 650 mg of acetaminophen and 50-100 mg diphenhydramine hydrochloride will be administered 30 to 60 minutes prior to starting each infusion of rituximab. The first rituximab infusion should be started at 50 mg/hr, and increased in 50-mg/hr increments every 30 minutes to a maximum rate of 400 mg/hr. If this rate of escalation is well tolerated the second and subsequent infusions can begin at a rate of 100 mg/hr and increase in 100 mg/hr increments every 30 minutes to a maximum of 400 mg/hr. CAUTION: DO NOT ADMINISTER AS AN INTRAVENOUS PUSH OR BOLUS.
arm group label: Venetoclax plus DA-EPOCH-R
other name: Rituxan
other name: IDEC-C2B8
other name: chimeric anti-CD20 monoclonal antibody
intervention type: Drug
intervention name: Etoposide
description: Etoposide will be obtained from commercial supply, and will be given for a total of 6 cycles for all patients. The drug will be given by IV route.
arm group label: Venetoclax plus DA-EPOCH-R
other name: VP-16
other name: VePesid
other name: etopophos
other name: toposar
intervention type: Drug
intervention name: Vincristine Sulfate
description: Vincristine Sulfate will be obtained from commercial supply, and will be given for a total of 6 cycles for all patients. The drug will be given by IV route.
arm group label: Venetoclax plus DA-EPOCH-R
other name: LCR
other name: VCR
intervention type: Drug
intervention name: Cyclophosphamide
description: Cyclophosphamide will be obtained from commercial supply, and will be given for a total of 6 cycles for all patients. The drug will be given by IV route.
arm group label: Venetoclax plus DA-EPOCH-R
other name: cytoxan
intervention type: Drug
intervention name: Prednisone
description: Prednisone will be obtained from commercial supply, and will be given for a total of 6 cycles for all patients. Prednisone will be given orally.
arm group label: Venetoclax plus DA-EPOCH-R
other name: Deltasone
other name: Orasone
other name: Paracort
other name: Cortan
intervention type: Drug
intervention name: Doxorubicin Hydrochloride
description: Doxorubicin Hydrochloride will be obtained from commercial supply, and will be given for a total of 6 cycles for all patients. The drug will be given by IV route.
arm group label: Venetoclax plus DA-EPOCH-R
other name: Hydroxydaunomycin Hydrochloride
other name: Hydroxydoxorubicin Hydrochloride
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: John P. Leonard, M.D.
role: Study Chair
affiliation: Weill Medical College of Cornell University
last name: Jeremy S. Abramson, M.D.
role: Study Chair
affiliation: Massachusetts General Hospital
last name: Sarah Rutherford, M.D.
role: Principal Investigator
affiliation: Weill Medical College of Cornell University
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, B-Cell
mesh term: Lymphoma, Large B-Cell, Diffuse
mesh term: Aggression
mesh term: Prednisone
mesh term: Cyclophosphamide
mesh term: Rituximab
mesh term: Doxorubicin
mesh term: Liposomal doxorubicin
mesh term: Etoposide
mesh term: Vincristine
mesh term: Venetoclax
sharing ipd: No