<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/NCT04464798</url>
  </required_header>
  <id_info>
    <org_study_id>CC-220-NHL-001</org_study_id>
    <secondary_id>U1111-1254-1772</secondary_id>
    <secondary_id>2020-000354-10</secondary_id>
    <nct_id>NCT04464798</nct_id>
  </id_info>
  <brief_title>A Dose Finding and Safety Study of CC-220, Alone and in Combination With an Anti-CD20 Monoclonal Antibody (mAb) in Subjects With Relapsed or Refractory Lymphomas</brief_title>
  <official_title>A Phase 1/2, Multicenter, Open-label Study to Assess Safety, Pharmacokinetics, and Preliminary Efficacy of CC-220, Alone and in Combination With an Anti-CD20 Monoclonal Antibody (mAb) in Subjects With Relapsed or Refractory Lymphomas.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Celgene</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Celgene</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This Phase 1/2, multicenter, open-label study to evaluate CC-220 alone, as well as in&#xD;
      combination with an anti-CD20 mAb (rituximab or obinutuzumab) in subjects with relapsed or&#xD;
      refractory (R/R) lymphoma. Subjects must have received at least 2 prior lines of therapy, and&#xD;
      have at least one measurable lesion according to Lugano 2014 classification.&#xD;
&#xD;
      Study will consist of two parts: Part 1 (Dose Escalation) which will be followed by Part 2&#xD;
      (Dose Expansion).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">November 11, 2020</start_date>
  <completion_date type="Anticipated">January 2, 2025</completion_date>
  <primary_completion_date type="Actual">March 28, 2023</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Tolerated Dose (MTD)</measure>
    <time_frame>During the First cycle (each cycle is 28 days)</time_frame>
    <description>is defined as the dose that satisfies the escalation with overdose control (EWOC) criterion that the posterior probability to have excessive toxicity is less than 25% and has the highest probability of dose-limiting toxicity (DLT) rate being in the target interval (0.16 to 0.33)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Recommended Phase 2 Dose (RP2D)</measure>
    <time_frame>During the first Cycle (each cycle is 28 days)</time_frame>
    <description>is defined as the dose that will be selected for dose expansion based on PK/Pd and MTD</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse Events (AEs)</measure>
    <time_frame>From first dose to 28 days after last subject discontinues study treatment</time_frame>
    <description>An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics - Cmax</measure>
    <time_frame>At Cycle1 Day15 and Cycle2 Day15 (each cycle is 28 days)</time_frame>
    <description>Maximum plasma concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics - Ctrough</measure>
    <time_frame>At Cycle1 Day15 and Cycle2 Day15 (each cycle is 28 days)</time_frame>
    <description>Observed plasma concentration at the end of the dosing interval</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics - AUC(TAU)</measure>
    <time_frame>At Cycle1 Day15 and Cycle2 Day15 (each cycle is 28 days)</time_frame>
    <description>Area under the plasma concentration-time curve from time zero to tau, where tau is the dosing interval</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics - tmax</measure>
    <time_frame>At Cycle1 Day15 and Cycle2 Day15 (each cycle is 28 days)</time_frame>
    <description>Time to maximum plasma concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics - CLT/F</measure>
    <time_frame>At Cycle1 Day15 and Cycle2 Day15 (each cycle is 28 days)</time_frame>
    <description>Apparent total plasma clearance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best Overall Response Rate (ORR)</measure>
    <time_frame>Approximately 5 years</time_frame>
    <description>is defined as the proportion of subjects with best overall response as either CR or partial response (PR) before subsequent anti-lymphoma therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complete Response Rate (CRR)</measure>
    <time_frame>Approximately 5 years</time_frame>
    <description>is defined as the proportion of subjects experiencing CR before receiving any subsequent anti-lymphoma therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Response (TTR)</measure>
    <time_frame>Approximately 5 years</time_frame>
    <description>is defined as the time from enrollment dose date to the date of first documented response (≥ PR)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR)</measure>
    <time_frame>Approximately 5 years</time_frame>
    <description>is defined as the time from first dose date to the date of first documented response (≥ PR)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS)</measure>
    <time_frame>Approximately 5 years</time_frame>
    <description>is defined as the time from enrollment date to the first occurrence of disease progression or death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Approximately 5 years</time_frame>
    <description>is defined as the time from enrollment date to death from any cause</description>
  </secondary_outcome>
  <number_of_arms>7</number_of_arms>
  <enrollment type="Actual">62</enrollment>
  <condition>Lymphoma</condition>
  <arm_group>
    <arm_group_label>Cohort A- Monotherapy in R/R lymphoma subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects with Relapsed or Refractory (R/R) lymphoma who have been allocated to Cohort A will receive CC-220 monotherapy (MonoT). Oral CC-220 at dose specified by cohort dose level from Day 1 to 21 of each 28-day cycle, up to PD or a maximum of 24 cycles.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort B- CC-220 and rituximab in R/R B-Cell NHL subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects with R/R B-cell Non Hodgkin Lymphoma (NHL) who have been allocated to Cohort B will receive CC-220 in combination with rituximab.&#xD;
Oral CC-220 at dose specified by cohort dose level from Day 1 to 21 of each 28-day cycle up to PD or maximum 24 cycles.&#xD;
Rituximab will be administered at 375 mg/m2 IV at C1D1 and then on D8, D15, and D22 of C1 and then every 28-day cycle at D1 from C2 to C5, either by SC administration at a dose of 1400 mg or by IV infusion at a dose of 375 mg/m2.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort C - CC-220 and obinutuzumab in R/R FL or MZL subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects with R/R FL (Grade 1 to 3a) or MZL who have been allocated to Cohort C will receive CC-220 in combination with obinutuzumab.&#xD;
Oral CC-220 at dose specified by cohort dose level from Day 1 to 21 of each 28-day cycle, up to PD or a maximum of 12 cycles.&#xD;
Obinutuzumab will be administered at 1000 mg at C1D1, D8, and D15, and on D1 of every 28-day cycle from C2 to C6.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort D -CC-220 monotherapy in participants with aggressive B-cell lymphoma and follicular lymphoma</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort E - CC-220 and rituximab in participants with aggressive B-cell lymphoma</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort F - CC-220 and rituximab with follicular lymphoma grade 1-3a</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort G - CC-220 plus obinutuzumab in participants with follicular lymphoma grade 1-3a</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CC-220</intervention_name>
    <description>Oral</description>
    <arm_group_label>Cohort A- Monotherapy in R/R lymphoma subjects</arm_group_label>
    <arm_group_label>Cohort B- CC-220 and rituximab in R/R B-Cell NHL subjects</arm_group_label>
    <arm_group_label>Cohort C - CC-220 and obinutuzumab in R/R FL or MZL subjects</arm_group_label>
    <arm_group_label>Cohort D -CC-220 monotherapy in participants with aggressive B-cell lymphoma and follicular lymphoma</arm_group_label>
    <arm_group_label>Cohort E - CC-220 and rituximab in participants with aggressive B-cell lymphoma</arm_group_label>
    <arm_group_label>Cohort F - CC-220 and rituximab with follicular lymphoma grade 1-3a</arm_group_label>
    <arm_group_label>Cohort G - CC-220 plus obinutuzumab in participants with follicular lymphoma grade 1-3a</arm_group_label>
    <other_name>Iberdomide</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rituximab</intervention_name>
    <description>SC and IV infusion</description>
    <arm_group_label>Cohort B- CC-220 and rituximab in R/R B-Cell NHL subjects</arm_group_label>
    <arm_group_label>Cohort E - CC-220 and rituximab in participants with aggressive B-cell lymphoma</arm_group_label>
    <arm_group_label>Cohort F - CC-220 and rituximab with follicular lymphoma grade 1-3a</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Obinutuzumab</intervention_name>
    <description>IV Infusion</description>
    <arm_group_label>Cohort C - CC-220 and obinutuzumab in R/R FL or MZL subjects</arm_group_label>
    <arm_group_label>Cohort G - CC-220 plus obinutuzumab in participants with follicular lymphoma grade 1-3a</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Subjects must satisfy the following criteria to be enrolled in the study:&#xD;
&#xD;
          1. Is ≥ 18 years of age at the time of signing the informed consent form (ICF).&#xD;
&#xD;
          2. Has histologically confirmed (per local evaluation) diagnosis of lymphoma according to&#xD;
             2016 World Health Organization (WHO) classification including:&#xD;
&#xD;
               1. Cohort A: all subtypes including B-cell, T-cell and Natural killer (NK)-cell&#xD;
                  Non-Hodgkin lymphoma (NHL), and Classical Hodgkin lymphoma (cHL).&#xD;
&#xD;
               2. Cohort B: all B-cell NHL.&#xD;
&#xD;
               3. Cohort C: FL Grade 1-3a and MZL including extranodal marginal zone lymphoma&#xD;
                  (ENMZL) of mucosa-associated lymphoid tissue (MALT lymphoma), nodal marginal zone&#xD;
                  lymphoma (NMZL) and splenic marginal zone lymphoma (SMZL)&#xD;
&#xD;
               4. Cohort D: aggressive B-cell lymphoma and FL grade 1-3a&#xD;
&#xD;
               5. Cohort E: aggressive B-cell lymphoma including DLBCL NOS, high-grade B-cell&#xD;
                  lymphoma, with MYC and BCL2 and/or BCL6 rearrangements, Grade 3b FL and PMBCL&#xD;
&#xD;
               6. Cohorts F and G: FL Grade 1 to 3a&#xD;
&#xD;
          3. Relapsed or refractory disease according to the following definitions:&#xD;
&#xD;
               1. Aggressive B-cell lymphoma&#xD;
&#xD;
               2. Follicular lymphoma (FL) and Marginal zone lymphoma (MZL): following at least 2&#xD;
                  prior lines of systemic therapy (being previously exposed to at least 1 anti-CD20&#xD;
                  mAb and 1 alkylating agent).&#xD;
&#xD;
               3. Mantle cell lymphoma (MCL): following at least 2 prior lines of therapy including&#xD;
                  at least 1 immunochemotherapy and 1 bruton tyrosine kinase (BTK) inhibitor.&#xD;
&#xD;
               4. Peripheral T-cell lymphoma (PTCL): following at least 2 prior lines of therapy OR&#xD;
                  after 1 prior line of standard therapy and being not eligible for any other&#xD;
                  approved regimen.&#xD;
&#xD;
               5. Classical Hodgkin lymphoma (cHL): following at least 2 prior systemic lines of&#xD;
                  therapy and previously exposed to brentuximab vedotin and anti-PD1.&#xD;
&#xD;
               6. All other subtypes: following at least 2 prior lines of therapy.&#xD;
&#xD;
               7. Subjects previously treated with CAR-T therapy can be enrolled (irrespective of&#xD;
                  the indication).&#xD;
&#xD;
          4. Subjects must not be eligible for any other approved treatment for their underlying&#xD;
             lymphoma as assessed by the Investigator.&#xD;
&#xD;
          5. Must have measurable disease defined by at least 1 fluorodeoxyglucose (FDG)-avid&#xD;
             lesion for FDG-avid subtype and 1 bi-dimensionally measurable (&gt; 1.5 cm in longest&#xD;
             diameter) disease by computed tomography (CT) or magnetic resonance imaging (MRI), as&#xD;
             defined by the Lugano classification. Site of measurable disease cannot be previously&#xD;
             irradiated.&#xD;
&#xD;
          6. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.&#xD;
&#xD;
          7. Must have the following laboratory values:&#xD;
&#xD;
               1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L or ≥ 1.0 x 109/L&#xD;
&#xD;
               2. Hemoglobin (Hb) ≥ 8 g/dL.&#xD;
&#xD;
               3. Platelets (Plt) ≥ 75 x 109/L or ≥ 50 x 109/L&#xD;
&#xD;
               4. Aspartate aminotransferase / serum glutamic oxaloacetic transaminase (AST/SGOT)&#xD;
                  and alanine aminotransferase / serum glutamic pyruvic transaminase (ALT/SGPT) ≤&#xD;
                  2.5 x ULN.&#xD;
&#xD;
               5. Serum total bilirubin ≤ 1.5 ULN except in cases of Gilbert's syndrome, then ≤ 3.0&#xD;
                  ULN.&#xD;
&#xD;
               6. Estimated serum creatinine clearance of ≥ 50 mL/min&#xD;
&#xD;
          8. All subjects must:&#xD;
&#xD;
               1. Have an understanding that the study drug could have a potential teratogenic&#xD;
                  risk.&#xD;
&#xD;
               2. Agree to follow all requirements defined in the Pregnancy Prevention Program for&#xD;
                  CC-220 Pregnancy Prevention Plan for Subjects in Clinical Trials.&#xD;
&#xD;
          9. Females of childbearing potential (FCBP1) must:&#xD;
&#xD;
             a. Have 2 negative pregnancy tests as verified by the Investigator prior to starting&#xD;
             study treatment. She must agree to ongoing pregnancy testing during the course of the&#xD;
             study, and after end of study treatment.&#xD;
&#xD;
         10. Male subjects must:&#xD;
&#xD;
               1. Practice true abstinence2 or agree to use a condom during sexual contact with a&#xD;
                  pregnant female or a female of childbearing potential while participating in the&#xD;
                  study,&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        The presence of any of the following will exclude a subject from enrollment:&#xD;
&#xD;
          1. Any significant medical condition, active infection (including severe acute&#xD;
             respiratory syndrome coronavirus 2 [SARS-CoV-2) suspected or confirmed, laboratory&#xD;
             abnormality, or psychiatric illness that would prevent the subject from participating&#xD;
             in the study.&#xD;
&#xD;
          2. 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.&#xD;
&#xD;
          3. Life expectancy ≤ 3 months.&#xD;
&#xD;
          4. Diagnosis of lymphoblastic lymphoma.&#xD;
&#xD;
          5. Aggressive lymphoma relapse requiring immediate cytoreductive therapy to avoid&#xD;
             potential life-threatening consequences (eg, due to tumor location).&#xD;
&#xD;
          6. Prior Grade 3 or 4 infusion related reaction with rituximab (for Cohorts B, E and F)&#xD;
             or obinutuzumab (for Cohorts C and G).&#xD;
&#xD;
          7. Prior therapy with the cereblon-modulating drug CC-99282.&#xD;
&#xD;
          8. Chronic systemic immunosuppressive therapy or corticosteroids.&#xD;
&#xD;
          9. Prior ASCT ≤ 3 months prior to starting CC-220 or &gt; 3 months AND with unresolved,&#xD;
             Grade &gt; 1, treatment-related toxicity.&#xD;
&#xD;
         10. Prior allogeneic stem cell transplant with either standard or reduced intensity&#xD;
             conditioning ≤ 6 months prior to starting CC-220 or &gt; 6 months with unresolved, Grade&#xD;
             &gt; 1, treatment-related toxicity.&#xD;
&#xD;
         11. Hypersensitivity to the active substance or to murine proteins, or to any of the other&#xD;
             excipients of rituximab or obinutuzumab.&#xD;
&#xD;
         12. Known allergy to thalidomide, pomalidomide or lenalidomide.&#xD;
&#xD;
         13. Inability or unwilling to undergo protocol required thromboembolism prophylaxis.&#xD;
&#xD;
         14. Major surgery ≤ 2 weeks prior to starting CC-220;&#xD;
&#xD;
         15. Peripheral neuropathy ≥ Grade 2 (NCI CTCAE v5.0).&#xD;
&#xD;
         16. Documented or suspected central nervous system (CNS) involvement of disease.&#xD;
&#xD;
         17. Subject with clinically significant cardiac disease.&#xD;
&#xD;
         18. Known seropositivity for or active viral infection with human immunodeficiency virus&#xD;
             (HIV).&#xD;
&#xD;
         19. Known chronic active hepatitis B&#xD;
&#xD;
         20. History of other malignancy, unless the subject has been free of the disease for ≥ 3&#xD;
             years; exceptions to the ≥ 3-year time limit include history of the following:&#xD;
&#xD;
               1. Incidental histologic finding of prostate cancer (or prostate cancer that has&#xD;
                  been treated with curative intent&#xD;
&#xD;
        Other protocol defined inclusion/exclusion criteria could apply&#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>Bristol-Myers Squibb</last_name>
    <role>Study Director</role>
    <affiliation>Bristol-Myers Squibb</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Local Institution - 106</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 105</name>
      <address>
        <city>Lake Mary</city>
        <state>Florida</state>
        <zip>32746</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 102</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 100</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Rochester Cancer Center</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 103</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 203</name>
      <address>
        <city>Creteil</city>
        <zip>94010</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 200</name>
      <address>
        <city>Lillie Cedex</city>
        <zip>59037</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 201</name>
      <address>
        <city>Montpellier CEDEX 5</city>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 202</name>
      <address>
        <city>Nantes cedex 1</city>
        <zip>44093</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 204</name>
      <address>
        <city>Paris</city>
        <zip>75010</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 205</name>
      <address>
        <city>Pessac</city>
        <zip>33604</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 401</name>
      <address>
        <city>Berlin</city>
        <zip>12203</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 402</name>
      <address>
        <city>Leipzig</city>
        <zip>4103</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 403</name>
      <address>
        <city>Munster</city>
        <zip>48149</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 404</name>
      <address>
        <city>Wuerzburg</city>
        <zip>97080</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 300</name>
      <address>
        <city>Brescia</city>
        <zip>25123</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 303</name>
      <address>
        <city>Milano</city>
        <zip>20133</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 301</name>
      <address>
        <city>Pavia</city>
        <zip>27100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 302</name>
      <address>
        <city>Verona</city>
        <zip>37134</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 502</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 501</name>
      <address>
        <city>Seoul</city>
        <zip>06351</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 500</name>
      <address>
        <city>Seoul</city>
        <zip>5505</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 600</name>
      <address>
        <city>Niaosong District Kaohsiung City</city>
        <zip>83301</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 601</name>
      <address>
        <city>Taoyuan City</city>
        <zip>33305</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 602</name>
      <address>
        <city>Taoyuan City</city>
        <zip>40447</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Korea, Republic of</country>
    <country>Taiwan</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html</url>
    <description>BMS Clinical Trial Information</description>
  </link>
  <link>
    <url>http://www.BMSStudyConnect.com</url>
    <description>BMS Clinical Trial Patient Recruiting</description>
  </link>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>July 6, 2020</study_first_submitted>
  <study_first_submitted_qc>July 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 9, 2020</study_first_posted>
  <last_update_submitted>July 10, 2023</last_update_submitted>
  <last_update_submitted_qc>July 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 12, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Relapsed or Refractory Lymphomas</keyword>
  <keyword>Lymphomas</keyword>
  <keyword>CC-220</keyword>
  <keyword>Anti-CD20</keyword>
  <keyword>Monoclonal Antibody</keyword>
  <keyword>Pharmacokinetics</keyword>
  <keyword>Safety</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rituximab</mesh_term>
    <mesh_term>Obinutuzumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Information relating to our policy on data sharing and the process for requesting data can be found at the following link:&#xD;
https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>See Plan Description</ipd_time_frame>
    <ipd_access_criteria>See Plan Description</ipd_access_criteria>
    <ipd_url>https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/</ipd_url>
  </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/NCT04464798
org study id: CC-220-NHL-001
secondary id: U1111-1254-1772
secondary id: 2020-000354-10
nct id: NCT04464798
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This Phase 1/2, multicenter, open-label study to evaluate CC-220 alone, as well as in
      combination with an anti-CD20 mAb (rituximab or obinutuzumab) in subjects with relapsed or
      refractory (R/R) lymphoma. Subjects must have received at least 2 prior lines of therapy, and
      have at least one measurable lesion according to Lugano 2014 classification.

      Study will consist of two parts: Part 1 (Dose Escalation) which will be followed by Part 2
      (Dose Expansion).
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose (MTD)
time frame: During the First cycle (each cycle is 28 days)
description: is defined as the dose that satisfies the escalation with overdose control (EWOC) criterion that the posterior probability to have excessive toxicity is less than 25% and has the highest probability of dose-limiting toxicity (DLT) rate being in the target interval (0.16 to 0.33)
measure: Recommended Phase 2 Dose (RP2D)
time frame: During the first Cycle (each cycle is 28 days)
description: is defined as the dose that will be selected for dose expansion based on PK/Pd and MTD
measure: Adverse Events (AEs)
time frame: From first dose to 28 days after last subject discontinues study treatment
description: An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE.
measure: Pharmacokinetics - Cmax
time frame: At Cycle1 Day15 and Cycle2 Day15 (each cycle is 28 days)
description: Maximum plasma concentration
measure: Pharmacokinetics - Ctrough
time frame: At Cycle1 Day15 and Cycle2 Day15 (each cycle is 28 days)
description: Observed plasma concentration at the end of the dosing interval
measure: Pharmacokinetics - AUC(TAU)
time frame: At Cycle1 Day15 and Cycle2 Day15 (each cycle is 28 days)
description: Area under the plasma concentration-time curve from time zero to tau, where tau is the dosing interval
measure: Pharmacokinetics - tmax
time frame: At Cycle1 Day15 and Cycle2 Day15 (each cycle is 28 days)
description: Time to maximum plasma concentration
measure: Pharmacokinetics - CLT/F
time frame: At Cycle1 Day15 and Cycle2 Day15 (each cycle is 28 days)
description: Apparent total plasma clearance
measure: Best Overall Response Rate (ORR)
time frame: Approximately 5 years
description: is defined as the proportion of subjects with best overall response as either CR or partial response (PR) before subsequent anti-lymphoma therapy
measure: Complete Response Rate (CRR)
time frame: Approximately 5 years
description: is defined as the proportion of subjects experiencing CR before receiving any subsequent anti-lymphoma therapy
measure: Time to Response (TTR)
time frame: Approximately 5 years
description: is defined as the time from enrollment dose date to the date of first documented response (≥ PR)
measure: Duration of Response (DOR)
time frame: Approximately 5 years
description: is defined as the time from first dose date to the date of first documented response (≥ PR)
measure: Progression-free Survival (PFS)
time frame: Approximately 5 years
description: is defined as the time from enrollment date to the first occurrence of disease progression or death from any cause
measure: Overall Survival (OS)
time frame: Approximately 5 years
description: is defined as the time from enrollment date to death from any cause
arm group label: Cohort A- Monotherapy in R/R lymphoma subjects
arm group type: Experimental
description: Subjects with Relapsed or Refractory (R/R) lymphoma who have been allocated to Cohort A will receive CC-220 monotherapy (MonoT). Oral CC-220 at dose specified by cohort dose level from Day 1 to 21 of each 28-day cycle, up to PD or a maximum of 24 cycles.
arm group label: Cohort B- CC-220 and rituximab in R/R B-Cell NHL subjects
arm group type: Experimental
description: Subjects with R/R B-cell Non Hodgkin Lymphoma (NHL) who have been allocated to Cohort B will receive CC-220 in combination with rituximab.
Oral CC-220 at dose specified by cohort dose level from Day 1 to 21 of each 28-day cycle up to PD or maximum 24 cycles.
Rituximab will be administered at 375 mg/m2 IV at C1D1 and then on D8, D15, and D22 of C1 and then every 28-day cycle at D1 from C2 to C5, either by SC administration at a dose of 1400 mg or by IV infusion at a dose of 375 mg/m2.
arm group label: Cohort C - CC-220 and obinutuzumab in R/R FL or MZL subjects
arm group type: Experimental
description: Subjects with R/R FL (Grade 1 to 3a) or MZL who have been allocated to Cohort C will receive CC-220 in combination with obinutuzumab.
Oral CC-220 at dose specified by cohort dose level from Day 1 to 21 of each 28-day cycle, up to PD or a maximum of 12 cycles.
Obinutuzumab will be administered at 1000 mg at C1D1, D8, and D15, and on D1 of every 28-day cycle from C2 to C6.
arm group label: Cohort D -CC-220 monotherapy in participants with aggressive B-cell lymphoma and follicular lymphoma
arm group type: Experimental
arm group label: Cohort E - CC-220 and rituximab in participants with aggressive B-cell lymphoma
arm group type: Experimental
arm group label: Cohort F - CC-220 and rituximab with follicular lymphoma grade 1-3a
arm group type: Experimental
arm group label: Cohort G - CC-220 plus obinutuzumab in participants with follicular lymphoma grade 1-3a
arm group type: Experimental
intervention type: Drug
intervention name: CC-220
description: Oral
arm group label: Cohort A- Monotherapy in R/R lymphoma subjects
arm group label: Cohort B- CC-220 and rituximab in R/R B-Cell NHL subjects
arm group label: Cohort C - CC-220 and obinutuzumab in R/R FL or MZL subjects
arm group label: Cohort D -CC-220 monotherapy in participants with aggressive B-cell lymphoma and follicular lymphoma
arm group label: Cohort E - CC-220 and rituximab in participants with aggressive B-cell lymphoma
arm group label: Cohort F - CC-220 and rituximab with follicular lymphoma grade 1-3a
arm group label: Cohort G - CC-220 plus obinutuzumab in participants with follicular lymphoma grade 1-3a
other name: Iberdomide
intervention type: Drug
intervention name: Rituximab
description: SC and IV infusion
arm group label: Cohort B- CC-220 and rituximab in R/R B-Cell NHL subjects
arm group label: Cohort E - CC-220 and rituximab in participants with aggressive B-cell lymphoma
arm group label: Cohort F - CC-220 and rituximab with follicular lymphoma grade 1-3a
intervention type: Drug
intervention name: Obinutuzumab
description: IV Infusion
arm group label: Cohort C - CC-220 and obinutuzumab in R/R FL or MZL subjects
arm group label: Cohort G - CC-220 plus obinutuzumab in participants with follicular lymphoma grade 1-3a
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Bristol-Myers Squibb
role: Study Director
affiliation: Bristol-Myers Squibb
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: France
country: Germany
country: Italy
country: Korea, Republic of
country: Taiwan
country: United States
url: https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
description: BMS Clinical Trial Information
url: http://www.BMSStudyConnect.com
description: BMS Clinical Trial Patient Recruiting
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Rituximab
mesh term: Obinutuzumab
sharing ipd: Yes
ipd description: Information relating to our policy on data sharing and the process for requesting data can be found at the following link:
https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: See Plan Description
ipd access criteria: See Plan Description
ipd url: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/