<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/NCT03829111</url>
  </required_header>
  <id_info>
    <org_study_id>18523</org_study_id>
    <secondary_id>NCI-2019-00248</secondary_id>
    <secondary_id>18523</secondary_id>
    <secondary_id>P30CA033572</secondary_id>
    <nct_id>NCT03829111</nct_id>
  </id_info>
  <brief_title>CBM588, Nivolumab, and Ipilimumab in Treating Patients With Stage IV or Advanced Kidney Cancer</brief_title>
  <official_title>Pilot Study to Evaluate the Biologic Effect of CBM588 in Combination With Nivolumab/Ipilimumab for Patients With Metastatic Renal Cell Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>City of Hope Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>City of Hope Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase I trial studies how well CBM588 works when given together with nivolumab and&#xD;
      ipilimumab in treating patients with kidney cancer that is stage IV or has spread to other&#xD;
      places in the body (advanced). CBM588 is a probiotic that may help to increase the effect of&#xD;
      immunotherapy. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab,&#xD;
      may help the body's immune system attack the cancer, and may interfere with the ability of&#xD;
      tumor cells to grow and spread. Giving CBM588, nivolumab, and ipilimumab may work better in&#xD;
      treating patients with kidney cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the effect of clostridium butyricum CBM 588 probiotic strain (CBM588) (in&#xD;
      combination with nivolumab/ipilimumab) on the gut microbiome in patients with metastatic&#xD;
      renal cell carcinoma (mRCC).&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate the effect of CBM588 on the clinical efficacy of the nivolumab/ipilimumab&#xD;
      combination.&#xD;
&#xD;
      II. To assess the effect of CBM588 on systemic immunomodulation of the nivolumab/ipilimumab&#xD;
      combination in patients with mRCC.&#xD;
&#xD;
      III. To assess the effect of CBM588 on toxicities such as diarrhea and nausea using Common&#xD;
      Terminology Criteria for Adverse Events (CTCAE) version (v) 5 criteria with the&#xD;
      nivolumab/ipilimumab combination in patients with mRCC.&#xD;
&#xD;
      OUTLINE: Patients are randomized to 1 of 2 arms.&#xD;
&#xD;
      ARM I: Patients receive nivolumab intravenously (IV) over 30 minutes and ipilimumab IV over&#xD;
      30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of&#xD;
      disease progression or unacceptable toxicity. Beginning in cycle 5, patients receive&#xD;
      nivolumab IV over 30 minutes on day 1. Cycles repeat every 28 days in the absence of disease&#xD;
      progression or unacceptable toxicity.&#xD;
&#xD;
      ARM II: Patients receive clostridium butyricum CBM 588 probiotic strain orally (PO) twice&#xD;
      daily (BID), nivolumab IV over 30 minutes on day 1, and ipilimumab IV over 30 minutes on day&#xD;
      1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression&#xD;
      or unacceptable toxicity. Beginning in cycle 5, treatment with clostridium butyricum CBM 588&#xD;
      probiotic strain and nivolumab repeats every 28 days in the absence of disease progression or&#xD;
      unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 30 days and periodically&#xD;
      thereafter.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">May 14, 2019</start_date>
  <completion_date type="Anticipated">December 11, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 11, 2023</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Bifidobacterium composition of stool</measure>
    <time_frame>Baseline up to week 12</time_frame>
    <description>Will be assessed for patients on both arms.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Shannon index</measure>
    <time_frame>Baseline up to week 12</time_frame>
    <description>Using translational methods, will compute the Shannon index at baseline for a comparison of microbial diversity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best overall response</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST). The association between treatment arm and overall response as per RECIST criteria (response observed versus [vs] not observed) will be examined using Fisher's exact test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>From enrollment to progression, assessed up to 2 years</time_frame>
    <description>The difference in progression free survival across the two groups will be explored graphically using Kaplan-Meier survival plots. Median PFS time for each of the two arms will be reported and Cox proportional hazards model will be used to estimate the hazard ratio and its confidence interval.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in proportion of circulating regulatory T-cells (Tregs)</measure>
    <time_frame>Baseline up to 2 years</time_frame>
    <description>Using translational methods will estimate the proportion of Tregs in the blood. This will be assessed graphically across serial timepoints of blood collection to ascertain any trends. Will compare the proportion of circulating Tregs with nivolumab/ipilimumab alone versus nivolumab/ipilimumab with clostridium butyricum CBM 588 probiotic strain (CBM588).</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in proportion of circulating myeloid-derived suppressor cells (MDSCs)</measure>
    <time_frame>Baseline up to 2 years</time_frame>
    <description>Using translational methods will estimate the proportion of MDSCs in the blood. This will be assessed graphically across serial timepoints of blood collection to ascertain any trends. Will compare the proportion of circulating MDSCs with nivolumab/ipilimumab alone versus nivolumab/ipilimumab with CBM588.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in IL-6, IL-8, and other cytokines/chemokines levels</measure>
    <time_frame>Baseline up to 2 years</time_frame>
    <description>Using translational methods will estimate the proportion of serum cytokines in the blood. This will be assessed graphically across serial timepoints of blood collection to ascertain any trends. Will compare the IL-6, IL-8, and other cytokines/chemokines with nivolumab/ipilimumab alone versus nivolumab/ipilimumab with CBM588.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in toxicities</measure>
    <time_frame>Baseline up to 2 years</time_frame>
    <description>Will compare toxicities, such as diarrhea and nausea, using Common Terminology Criteria for Adverse Events version 5 with nivolumab/ipilimumab alone versus nivolumab/ipilimumab with CBM588.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Advanced Renal Cell Carcinoma</condition>
  <condition>Clear Cell Renal Cell Carcinoma</condition>
  <condition>Metastatic Renal Cell Carcinoma</condition>
  <condition>Stage III Renal Cell Cancer AJCC v8</condition>
  <condition>Stage IV Renal Cell Cancer AJCC v8</condition>
  <condition>Unresectable Renal Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Arm I (nivolumab, ipilimumab)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning in cycle 5, patients receive nivolumab IV over 30 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm II (CBM588, nivolumab, ipilimumab)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive clostridium butyricum CBM 588 probiotic strain PO BID, nivolumab IV over 30 minutes on day 1, and ipilimumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning in cycle 5, treatment with clostridium butyricum CBM 588 probiotic strain and nivolumab repeats every 28 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Clostridium butyricum CBM 588 Probiotic Strain</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm II (CBM588, nivolumab, ipilimumab)</arm_group_label>
    <other_name>C. butyricum CBM 588 Probiotic Strain</other_name>
    <other_name>C. butyricum MIYAIRI Strain</other_name>
    <other_name>C. butyricum Strain MIYAIRI 588</other_name>
    <other_name>CBM 588</other_name>
    <other_name>CBM588</other_name>
    <other_name>Clostridium butyricum MIYAIRI 588</other_name>
    <other_name>Clostridium butyricum MIYAIRI 588 Probiotic Strain</other_name>
    <other_name>MIYAIRI 588</other_name>
    <other_name>MIYAIRI 588 Strain of C. butyricum</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Ipilimumab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (nivolumab, ipilimumab)</arm_group_label>
    <arm_group_label>Arm II (CBM588, nivolumab, ipilimumab)</arm_group_label>
    <other_name>Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody</other_name>
    <other_name>BMS-734016</other_name>
    <other_name>MDX-010</other_name>
    <other_name>MDX-CTLA4</other_name>
    <other_name>Yervoy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Nivolumab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (nivolumab, ipilimumab)</arm_group_label>
    <arm_group_label>Arm II (CBM588, nivolumab, ipilimumab)</arm_group_label>
    <other_name>BMS-936558</other_name>
    <other_name>MDX-1106</other_name>
    <other_name>NIVO</other_name>
    <other_name>ONO-4538</other_name>
    <other_name>Opdivo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Be willing and able to provide informed consent for the trial&#xD;
&#xD;
          -  Histological confirmation of RCC with a clear-cell component&#xD;
&#xD;
          -  Advanced (not amenable to curative surgery or radiation therapy) or metastatic&#xD;
             (American Joint Committee on Cancer [AJCC] stage IV) RCC&#xD;
&#xD;
          -  Intermediate or poor risk disease by International Metastatic RCC Database Consortium&#xD;
             (IMDC) classification&#xD;
&#xD;
          -  No prior systemic therapy for RCC with the following exception:&#xD;
&#xD;
               -  One prior adjuvant or neoadjuvant therapy for completely resectable RCC if such&#xD;
                  therapy did not include an agent that targets PD-1 or PD-L1 and if recurrence&#xD;
                  occurred at least 6 months after the last dose of adjuvant or neoadjuvant therapy&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status &lt; 2&#xD;
&#xD;
          -  Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1&#xD;
&#xD;
          -  Any ethnicity or race&#xD;
&#xD;
          -  Calculated creatinine clearance &gt;= 30 milliliters per minute (mL/min) per the&#xD;
             Cockcroft and Gault formula or serum creatinine &lt; 1.5 x upper limit of normal (ULN)&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) &lt; 3 x ULN (&lt; 5 x&#xD;
             ULN if liver metastases are present)&#xD;
&#xD;
          -  Total bilirubin &lt; 1.5 x ULN (except subjects with Gilbert syndrome, who can have total&#xD;
             bilirubin up to 3.0 mg/dL)&#xD;
&#xD;
          -  White blood cells (WBC) &gt; 2,000/mm^3&#xD;
&#xD;
          -  Neutrophils &gt; 1,500/mm^3&#xD;
&#xD;
          -  Platelets &gt; 100,000/mm^3&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Presence of untreated brain metastases. Patients with treated brain metastases must be&#xD;
             stable for 4 weeks after completion of treatment and have documented stability on&#xD;
             pre-study imaging. Patients must have no clinical symptoms from brain metastases and&#xD;
             have no requirement for systemic corticosteroids amounting to &gt; 10 mg/day of&#xD;
             prednisone or its equivalent for at least 2 weeks prior to first dose of study drug.&#xD;
             Patients with known leptomeningeal metastases are excluded, even if treated&#xD;
&#xD;
               -  Not recovered to =&lt; grade 1 toxicities related to any prior therapy before&#xD;
                  administration of study drug&#xD;
&#xD;
          -  Favorable risk disease by IMDC classification&#xD;
&#xD;
          -  Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4&#xD;
             antibody, or any other antibody or drug specifically targeting T-cell co-stimulation&#xD;
             or checkpoint pathways&#xD;
&#xD;
          -  Any active or recent history of a known or suspected autoimmune disease or recent&#xD;
             history of a syndrome that required systemic corticosteroids (&gt; 10 mg daily prednisone&#xD;
             equivalent) or immunosuppressive medications except for syndromes which would not be&#xD;
             expected to recur in the absence of an external trigger. Subjects with vitiligo or&#xD;
             type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only&#xD;
             requiring hormone replacement are permitted to enroll&#xD;
&#xD;
          -  Active interstitial lung disease (ILD)/pneumonitis or history of ILD/pneumonitis&#xD;
             requiring treatment with systemic steroids&#xD;
&#xD;
          -  Baseline pulse oximetry less than 92% &quot;on room air&quot;&#xD;
&#xD;
          -  Current use, or intent to use, probiotics, yogurt or bacterial fortified foods during&#xD;
             the period of treatment&#xD;
&#xD;
          -  Any condition requiring systemic treatment with corticosteroids (&gt; 10 mg daily&#xD;
             prednisone equivalents) or other immunosuppressive medications within 14 days prior to&#xD;
             first dose of study drug. Inhaled steroids and adrenal replacement steroid doses &gt; 10&#xD;
             mg daily prednisone equivalents are permitted in the absence of active autoimmune&#xD;
             disease&#xD;
&#xD;
          -  Uncontrolled adrenal insufficiency&#xD;
&#xD;
          -  Known medical condition (e.g., a condition associated with diarrhea or acute&#xD;
             diverticulitis) that, in the investigator's opinion, would increase the risk&#xD;
             associated with study participation or study drug administration or interfere with the&#xD;
             interpretation of safety results&#xD;
&#xD;
          -  Not recovered to =&lt; grade 1 toxicities related to any prior therapy before&#xD;
             administration of study drug&#xD;
&#xD;
          -  Women who are pregnant or breastfeeding&#xD;
&#xD;
          -  History of myocarditis or congestive heart failure (as defined by New York Heart&#xD;
             Association functional classification III or IV), as well as unstable angina, serious&#xD;
             uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction 6&#xD;
             months prior to study entry&#xD;
&#xD;
          -  White blood cells (WBC) &lt; 2,000/mm^3&#xD;
&#xD;
          -  Neutrophils &lt; 1,500/mm^3&#xD;
&#xD;
          -  Platelets &lt; 100,000/mm^3&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) &gt; 3 x upper limit&#xD;
             of normal (ULN) (&gt; 5 x ULN if liver metastases are present)&#xD;
&#xD;
          -  Total bilirubin &gt; 1.5 x ULN (except subjects with Gilbert syndrome, who can have total&#xD;
             bilirubin 3.0 mg/dL)&#xD;
&#xD;
          -  Calculated creatinine clearance &lt; 30 millimeters per minute (mL/min) per the Cockcroft&#xD;
             and Gault formula or serum creatinine &gt; 1.5 x upper limit of normal (ULN)&#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>Sumanta K Pal</last_name>
    <role>Principal Investigator</role>
    <affiliation>City of Hope Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>City of Hope Medical Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>February 1, 2019</study_first_submitted>
  <study_first_submitted_qc>February 1, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 4, 2019</study_first_posted>
  <last_update_submitted>September 7, 2023</last_update_submitted>
  <last_update_submitted_qc>September 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 11, 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>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Renal Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nivolumab</mesh_term>
    <mesh_term>Ipilimumab</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03829111
org study id: 18523
secondary id: NCI-2019-00248
secondary id: 18523
secondary id: P30CA033572
nct id: NCT03829111
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This phase I trial studies how well CBM588 works when given together with nivolumab and
      ipilimumab in treating patients with kidney cancer that is stage IV or has spread to other
      places in the body (advanced). CBM588 is a probiotic that may help to increase the effect of
      immunotherapy. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab,
      may help the body's immune system attack the cancer, and may interfere with the ability of
      tumor cells to grow and spread. Giving CBM588, nivolumab, and ipilimumab may work better in
      treating patients with kidney cancer.
PRIMARY OBJECTIVES:

      I. To determine the effect of clostridium butyricum CBM 588 probiotic strain (CBM588) (in
      combination with nivolumab/ipilimumab) on the gut microbiome in patients with metastatic
      renal cell carcinoma (mRCC).

      SECONDARY OBJECTIVES:

      I. To evaluate the effect of CBM588 on the clinical efficacy of the nivolumab/ipilimumab
      combination.

      II. To assess the effect of CBM588 on systemic immunomodulation of the nivolumab/ipilimumab
      combination in patients with mRCC.

      III. To assess the effect of CBM588 on toxicities such as diarrhea and nausea using Common
      Terminology Criteria for Adverse Events (CTCAE) version (v) 5 criteria with the
      nivolumab/ipilimumab combination in patients with mRCC.

      OUTLINE: Patients are randomized to 1 of 2 arms.

      ARM I: Patients receive nivolumab intravenously (IV) over 30 minutes and ipilimumab IV over
      30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of
      disease progression or unacceptable toxicity. Beginning in cycle 5, patients receive
      nivolumab IV over 30 minutes on day 1. Cycles repeat every 28 days in the absence of disease
      progression or unacceptable toxicity.

      ARM II: Patients receive clostridium butyricum CBM 588 probiotic strain orally (PO) twice
      daily (BID), nivolumab IV over 30 minutes on day 1, and ipilimumab IV over 30 minutes on day
      1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression
      or unacceptable toxicity. Beginning in cycle 5, treatment with clostridium butyricum CBM 588
      probiotic strain and nivolumab repeats every 28 days in the absence of disease progression or
      unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days and periodically
      thereafter.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in Bifidobacterium composition of stool
time frame: Baseline up to week 12
description: Will be assessed for patients on both arms.
measure: Change in Shannon index
time frame: Baseline up to week 12
description: Using translational methods, will compute the Shannon index at baseline for a comparison of microbial diversity.
measure: Best overall response
time frame: Up to 2 years
description: Will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST). The association between treatment arm and overall response as per RECIST criteria (response observed versus [vs] not observed) will be examined using Fisher's exact test.
measure: Progression-free survival (PFS)
time frame: From enrollment to progression, assessed up to 2 years
description: The difference in progression free survival across the two groups will be explored graphically using Kaplan-Meier survival plots. Median PFS time for each of the two arms will be reported and Cox proportional hazards model will be used to estimate the hazard ratio and its confidence interval.
measure: Change in proportion of circulating regulatory T-cells (Tregs)
time frame: Baseline up to 2 years
description: Using translational methods will estimate the proportion of Tregs in the blood. This will be assessed graphically across serial timepoints of blood collection to ascertain any trends. Will compare the proportion of circulating Tregs with nivolumab/ipilimumab alone versus nivolumab/ipilimumab with clostridium butyricum CBM 588 probiotic strain (CBM588).
measure: Change in proportion of circulating myeloid-derived suppressor cells (MDSCs)
time frame: Baseline up to 2 years
description: Using translational methods will estimate the proportion of MDSCs in the blood. This will be assessed graphically across serial timepoints of blood collection to ascertain any trends. Will compare the proportion of circulating MDSCs with nivolumab/ipilimumab alone versus nivolumab/ipilimumab with CBM588.
measure: Change in IL-6, IL-8, and other cytokines/chemokines levels
time frame: Baseline up to 2 years
description: Using translational methods will estimate the proportion of serum cytokines in the blood. This will be assessed graphically across serial timepoints of blood collection to ascertain any trends. Will compare the IL-6, IL-8, and other cytokines/chemokines with nivolumab/ipilimumab alone versus nivolumab/ipilimumab with CBM588.
measure: Change in toxicities
time frame: Baseline up to 2 years
description: Will compare toxicities, such as diarrhea and nausea, using Common Terminology Criteria for Adverse Events version 5 with nivolumab/ipilimumab alone versus nivolumab/ipilimumab with CBM588.
arm group label: Arm I (nivolumab, ipilimumab)
arm group type: Active Comparator
description: Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning in cycle 5, patients receive nivolumab IV over 30 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
arm group label: Arm II (CBM588, nivolumab, ipilimumab)
arm group type: Experimental
description: Patients receive clostridium butyricum CBM 588 probiotic strain PO BID, nivolumab IV over 30 minutes on day 1, and ipilimumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning in cycle 5, treatment with clostridium butyricum CBM 588 probiotic strain and nivolumab repeats every 28 days in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Clostridium butyricum CBM 588 Probiotic Strain
description: Given PO
arm group label: Arm II (CBM588, nivolumab, ipilimumab)
other name: C. butyricum CBM 588 Probiotic Strain
other name: C. butyricum MIYAIRI Strain
other name: C. butyricum Strain MIYAIRI 588
other name: CBM 588
other name: CBM588
other name: Clostridium butyricum MIYAIRI 588
other name: Clostridium butyricum MIYAIRI 588 Probiotic Strain
other name: MIYAIRI 588
other name: MIYAIRI 588 Strain of C. butyricum
intervention type: Biological
intervention name: Ipilimumab
description: Given IV
arm group label: Arm I (nivolumab, ipilimumab)
arm group label: Arm II (CBM588, nivolumab, ipilimumab)
other name: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
other name: BMS-734016
other name: MDX-010
other name: MDX-CTLA4
other name: Yervoy
intervention type: Biological
intervention name: Nivolumab
description: Given IV
arm group label: Arm I (nivolumab, ipilimumab)
arm group label: Arm II (CBM588, nivolumab, ipilimumab)
other name: BMS-936558
other name: MDX-1106
other name: NIVO
other name: ONO-4538
other name: Opdivo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sumanta K Pal
role: Principal Investigator
affiliation: City of Hope Medical Center
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Renal Cell
mesh term: Nivolumab
mesh term: Ipilimumab