<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/NCT03283202</url>
  </required_header>
  <id_info>
    <org_study_id>CC-122-DLBCL-002</org_study_id>
    <secondary_id>U1111-1201-1994</secondary_id>
    <secondary_id>2016-003778-42</secondary_id>
    <nct_id>NCT03283202</nct_id>
  </id_info>
  <brief_title>Study of Safety and Efficacy of Avadomide (CC-122) Combined With RCHOP for Newly-diagnosed DLBCL With Poor Risk Factors</brief_title>
  <official_title>A Phase 1/2 Open-Label Multicenter Study of Avadomide (CC-122) in Combination With R-CHOP-21 for Previously Untreated Poor Risk (IPI&gt;=3) Diffuse Large B-Cell Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Celgene</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Celgene</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 Phase 1/2 study of avadomide (CC-122) in combination with rituximab,&#xD;
      cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy, for&#xD;
      first-line treatment of patients with Diffuse B-Cell Large B-Cell Lymphoma (DLBCL) that has&#xD;
      poor risk factors. Approximately 40% of patients diagnosed with DLBCL are not cured with&#xD;
      R-CHOP alone and would need additional treatment for DLBCL in the future. The addition of the&#xD;
      experimental drug avadomide (CC-122) with R-CHOP could help in controlling DLBCL in this&#xD;
      patient population.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This research study is for patients who have been newly diagnosed with diffuse large B-cell&#xD;
      lymphoma DLBCL and are receiving treatment for the first time.&#xD;
&#xD;
      This study will be conducted in two phases. Phase 1 will test the safety of increasing dose&#xD;
      levels of avadomide (CC-122) when given in combination with R-CHOP-21 therapy to identify an&#xD;
      appropriate dose and schedule for further evaluation in Phase 2. Phase 2 will evaluate the&#xD;
      rate of complete response when adding avadomide (CC-122) to the R-CHOP-21 regimen in&#xD;
      first-line treatment of patients with poor risk DLBCL.&#xD;
&#xD;
      This study is separated into three periods: the Screening period, the Treatment period and&#xD;
      the Follow-up period. Before the patient can receive the drug the doctor will perform test to&#xD;
      find out whether he/she can participate in the study. This is done during the Screening&#xD;
      period. If the patient and the treating physician determine that the patient is eligible to&#xD;
      participate in the study, the patient will be registered in the study and receive avadomide&#xD;
      (CC-122) combined with R-CHOP.&#xD;
&#xD;
      In the Treatment period the patient will receive treatment for up to 6 treatment cycles. Each&#xD;
      treatment cycle is 21 days long. The full length of the treatment period will be&#xD;
      approximately 4 months.&#xD;
&#xD;
      The follow-up period begins when the patient has completed treatment or is discontinued for&#xD;
      any reason. During the follow-up period the patient will have fewer exams, test and visits.&#xD;
      The first follow-up visit will be 28 days after treatment is completed or discontinued. After&#xD;
      that, the follow-up visits will be every 3 months during the first year, then every 6 months&#xD;
      until the study is closed.&#xD;
&#xD;
      Upon completion of the Phase 1 portion of the study, a decision not to proceed with the Phase&#xD;
      2 portion was taken by the Sponsor. The decision to terminate the study after Phase 1 was not&#xD;
      based on any safety concerns that posed an unacceptable risk for this patient population and&#xD;
      no safety issues have been identified&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 4, 2017</start_date>
  <completion_date type="Actual">December 16, 2020</completion_date>
  <primary_completion_date type="Actual">July 30, 2019</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>Maximum Tolerated Dose/Maximum Administered Dose (MTD/MAD) (Phase 1)</measure>
    <time_frame>Through 6 cycles of treatment (approximately 18 weeks or 4 months)</time_frame>
    <description>Frequency of dose-limiting toxicities (DLTs) associated with the addition of avadomide (CC-122) to R-CHOP-21 therapy</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Complete Response Rate (CRR); Percentage of participants experiencing positron emission tomography (PET)-negative complete response (CR) (Phase 2)</measure>
    <time_frame>6 to 8 weeks after completion of treatment</time_frame>
    <description>CR is defined as target nodes/nodal masses regress to ≤ 1.5 cm in LDi; no extralymphatic sites of disease; no measurable lesions, no organ enlargement and normal morphology on bone marrow (BM) exam; immunohistochemically (IHC) negative</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate (ORR); Percentage of participants who achieve a PR or CR according to the Lugano criteria.</measure>
    <time_frame>6 to 8 weeks after completion of treatment</time_frame>
    <description>ORR is defined as the rate of the responses (including CR; see definition above for CR and PR; PR is defined as ≥ 50% decrease in sum of perpendicular diameters (SPD) of up to 6 target measurable nodes and extranodal sites. When a lesion is too small to measure on CT, assign 5 mm × 5 mm as the default value; When no longer visible, 0 × 0 mm; for a node &gt; 5 mm × 5 mm, but smaller than normal, use actual measurement for calculation; Absent/normal, regressed, but no increase in non measurable lesions; spleen must have regressed &gt; 50% in length beyond normal and no new lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ORR by Predictive Gene Signature</measure>
    <time_frame>6 to 8 weeks after completion of treatment</time_frame>
    <description>ORR by Predictive Gene Signature is defined as the correlation between baseline gene expression signatures and clinical response to study treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS)</measure>
    <time_frame>From enrollment up to 24 months after last subject is enrolled</time_frame>
    <description>PFS is defined as the time from enrollment to disease progression or death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Event-free Survival (EFS)</measure>
    <time_frame>At 12 and 24 months after enrollment</time_frame>
    <description>EFS is defined as the percentage of participants without event (relapse or progression, unplanned re-treatment of lymphoma after initial immunochemotherapy, or death from any cause)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Up to 24 months after enrollment</time_frame>
    <description>OS is defined as the time from enrollment until death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Events (AEs)</measure>
    <time_frame>From enrollment until at least 28 days after completion of 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 pre- existing condition) should be considered an AE.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">35</enrollment>
  <condition>Diffuse B-Cell Lymphoma</condition>
  <arm_group>
    <arm_group_label>Avadomide (CC-122) plus R-CHOP-21</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Avadomide (CC-122) by mouth (PO) at varying dose levels (Ph 1) on Days 1 through 5 and Days 8 through 12 plus Rituxan 375 mg/m2 by intravenous (IV) infusion, cyclophosphamide 750mg/m2 by IV infusion, doxorubicin 50 mg/m2 IV, vincristine 1.4 mg/m2 (max is 2.0 mg) IV and 100 mg PO prednisone/prednisolone on Days 1 through 5 of each 21-day treatment cycles for up to 6 total treatment cycles (approximately 18 weeks or 4 months)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Avadomide (CC-122)</intervention_name>
    <description>Avadomide (CC-122) by mouth at the assigned dose in Ph 1 starting on Day 1 for 5 consecutive days per week, followed by 2 days without avadomide (CC-122) administration (5/7) for the first two weeks of a 21-day treatment cycle. If the highest proposed dose level to be explored in Phase 1 is applied, the dosing regimen will be 5/7 days for all 3 weeks of each 21-day treatment cycle.</description>
    <arm_group_label>Avadomide (CC-122) plus R-CHOP-21</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rituximab</intervention_name>
    <description>Rituxan 375 mg/m2 on Day 1 by intravenous (IV) infusion of a 21-day treatment cycle for up to a total of 6 cycles</description>
    <arm_group_label>Avadomide (CC-122) plus R-CHOP-21</arm_group_label>
    <other_name>Rituxan, MabThera</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide 750mg/m2 by IV infusion</intervention_name>
    <description>Cyclophosphamide 750mg/m2 on Day 1 by IV infusion of a 21-day treatment cycle for up to a total of 6 cycles</description>
    <arm_group_label>Avadomide (CC-122) plus R-CHOP-21</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vincristine</intervention_name>
    <description>Vincristine 1.4 mg/m2 (maximum of 2.0 mg total) on Day 1 by IV bolus on Day 1 of a 21-day treatment cycle for up to a total of 6 cycles</description>
    <arm_group_label>Avadomide (CC-122) plus R-CHOP-21</arm_group_label>
    <other_name>Oncovin, Vincasar</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prednisone</intervention_name>
    <description>Prednisone 100 mg PO on Days 1 through 5 of each 21-day treatment or 100mg IV on Day 1 is also acceptable for up to a total of 6 cycles</description>
    <arm_group_label>Avadomide (CC-122) plus R-CHOP-21</arm_group_label>
    <other_name>Prednisolone</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        1. Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).&#xD;
&#xD;
        2. Subject has documented, histologically locally confirmed, previously untreated CD20+&#xD;
        DLBCL (NOS) and the following histologies; refer to the World Health Organization (WHO)&#xD;
        2016 classification (Appendix G):&#xD;
&#xD;
          1. DLBCL associated with chronic inflammation&#xD;
&#xD;
          2. Epstein-Barr virus positive (EBV+) of the elderly&#xD;
&#xD;
          3. T-cell/histiocyte-rich DLBCL 3. Subject is considered an appropriate candidate (per&#xD;
             Investigator assessment) for induction therapy with 6 cycles of R-CHOP-21&#xD;
             immunochemotherapy.&#xD;
&#xD;
             4. Subject has a performance status (PS) of 0-2 according to the Eastern Cooperative&#xD;
             Oncology Group (ECOG) scale. Subjects with ECOG PS of 3 may be included if decreased&#xD;
             PS is secondary to DLBCL only, and not to comorbidities.&#xD;
&#xD;
             5. Subject has poor-risk disease defined as International Prognostic Index (IPI) score&#xD;
             ≥ 3 (high-intermediate or high-risk classification) and has an age-adjusted IPI&#xD;
             defined as ≤ 60 age-adjusted IPI score of 2 with elevated LDH are eligible.&#xD;
&#xD;
             6. Subject has measurable disease on cross-sectional imaging by computed tomography&#xD;
             (CT) with at least one (post-biopsy) measurable lesion ≥ 2.0 cm in its longest&#xD;
             dimension.&#xD;
&#xD;
             7. Subject must appropriately be able to complete Screening assessments before&#xD;
             beginning treatment for DLBCL, in the judgement of the Investigator.&#xD;
&#xD;
             For subjects with bulky disease, B-symptoms, compressive disease, elevated bilirubin&#xD;
             due to lymphoma, rapidly progressing adenopathies, or worsening performance status,&#xD;
             pre-phase treatment with up to 100 mg/day prednisone, or equivalent, for a maximum of&#xD;
             10 days is permitted prior to beginning the treatment period, at the discretion of the&#xD;
             Investigator. A washout period is not required, however, the Screening positron&#xD;
             emission tomography (PET), CT, tumor biopsy (if needed), and bone marrow biopsy (if&#xD;
             needed) should be completed before initiating corticosteroids.&#xD;
&#xD;
             8. Subject's central laboratory values must fulfill the following requirements during&#xD;
             Screening: Blood product transfusions and hematopoietic growth factors may not be used&#xD;
             to meet eligibility criteria. Screening samples should not be collected within 14 days&#xD;
             after subject receives a blood product transfusion or growth factors.&#xD;
&#xD;
             If treatment needs to be urgently started and screening central laboratory results are&#xD;
             not available then local laboratory results may be used to confirm eligibility. In&#xD;
             these cases, the Celgene medical monitor must be consulted prior to beginning&#xD;
             treatment. The investigator must still ensure that samples for the central laboratory&#xD;
             are drawn before investigational product is administered and sent to the central&#xD;
             laboratory.&#xD;
&#xD;
             1. Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3 (1.5 x 109/L) unless secondary to&#xD;
             extensive bone marrow involvement by lymphoma (ie, ≥ 50%) as demonstrated by&#xD;
             unilateral bone marrow core biopsy performed during Screening or within 3 months prior&#xD;
             to signing the ICF. In the case of documented extensive bone marrow involvement an ANC&#xD;
             ≥ 1,000 cells/mm3 (1.0 x 109/L) is required.&#xD;
&#xD;
             2. Platelet count ≥ 100,000/mm3 (100 x 109/L) unless secondary to extensive bone&#xD;
             marrow involvement by lymphoma (ie, ≥ 50%) as demonstrated by unilateral bone marrow&#xD;
             core biopsy performed during Screening or within 3 months prior to signing the ICF. In&#xD;
             the case of documented extensive bone marrow involvement, a platelet count of ≥&#xD;
             75,000/ mm3 (75 x 109/L) is required.&#xD;
&#xD;
             3. Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≤ 3.0 x&#xD;
             upper limit of normal (ULN). In the case of documented liver involvement by lymphoma,&#xD;
             ALT/SGPT and AST/SGOT must be ≤ 5.0 x ULN.&#xD;
&#xD;
             4. Serum total bilirubin ≤ 2.0 mg/dL (34 μmol/L). In the case of Gilbert's syndrome,&#xD;
             or documented liver or pancreatic involvement by lymphoma, serum total bilirubin must&#xD;
             be ≤ 5.0 mg/dL (86 μmol/L).&#xD;
&#xD;
             5. Calculated creatinine clearance (CrCl) of ≥ 50 mL/min by the Cockcroft-Gault&#xD;
             formula.&#xD;
&#xD;
             9. Subject must understand and voluntarily sign an Informed Consent Form (ICF) prior&#xD;
             to any study-specific assessments/procedures being conducted.&#xD;
&#xD;
             10. Subject is willing and able to adhere to the study visit schedule and other&#xD;
             protocol requirements.&#xD;
&#xD;
             11. Sufficient tissue from diagnostic tumor/ lymph node biopsy (from within 2 months&#xD;
             prior to ICF signature) must be available for translational research purposes or&#xD;
             subject is willing to undergo core needle or incisional/ excisional biopsy during&#xD;
             Screening.&#xD;
&#xD;
             12. Females of childbearing potential (FCBP)1 must:&#xD;
&#xD;
               1. Agree to use two reliable forms of contraception simultaneously or to practice&#xD;
                  complete abstinence (True abstinence is acceptable when this is in line with the&#xD;
                  preferred and usual lifestyle of the subject. Periodic abstinence [eg calendar,&#xD;
                  ovulation, symptothermal or post-ovulation methods] and withdrawal are not&#xD;
                  acceptable methods of contraception.) from heterosexual contact during the&#xD;
                  following time periods related to this study: 1) for at least 28 days before&#xD;
                  starting avadomide (CC-122); 2) while taking avadomide (CC-122); 3) during dose&#xD;
                  interruptions; and 4) for at least 28 days after the last dose of avadomide&#xD;
                  (CC-122) as specified in the Pregnancy Prevention and Risk Management Plan&#xD;
                  (PPRMP)&#xD;
&#xD;
               2. Have a negative result confirmed for a medically supervised urine (or serum)&#xD;
                  pregnancy test (with a sensitivity of at least 25 mIU/mL) 10-14 days prior to the&#xD;
                  first dose of IP. A second pregnancy test performed within 24 hours prior to the&#xD;
                  first dose of IP must also be confirmed to be negative prior to IP&#xD;
                  administration.&#xD;
&#xD;
                    -  If urgent treatment is needed and requires a shorter window of screening,&#xD;
                       please immediately contact the medical monitor&#xD;
&#xD;
             13. Avoid conceiving for at least 12 months after the last dose of rituximab, or&#xD;
             according to the local rituximab Prescribing Information or Summary of Product&#xD;
             characteristics (SmPC); at least 28 days after the last dose of any other study drug.&#xD;
&#xD;
             1. Agree to ongoing pregnancy testing during the course of the study as outlined in&#xD;
             the PPRMP.&#xD;
&#xD;
             14. Male subjects must:&#xD;
&#xD;
               1. Practice complete abstinence (True abstinence is acceptable when this is in line&#xD;
                  with the preferred and usual lifestyle of the subject. Periodic abstinence [eg&#xD;
                  calendar, ovulation, symptothermal or post-ovulation methods] and withdrawal are&#xD;
                  not acceptable methods of contraception.) or agree to use a condom during sexual&#xD;
                  contact with a pregnant female or a FCBP for at least 12 months after the last&#xD;
                  dose of rituximab.&#xD;
&#xD;
               2. Agree to not donate semen or sperm for at least 12 months following the last dose&#xD;
                  of rituximab.&#xD;
&#xD;
             15. All subjects must:&#xD;
&#xD;
               1. Understand that avadomide (CC-122) could have a potential teratogenic risk.&#xD;
&#xD;
               2. Agree to abstain from donating blood while taking IP and for at least 28 days&#xD;
                  following discontinuation of IP.&#xD;
&#xD;
               3. Agree not to share IP with another person&#xD;
&#xD;
               4. Be counseled about pregnancy precautions and risks of fetal exposure and agree to&#xD;
                  requirements of the Pregnancy Prevention and Risk Management Plan (PPRMP)&#xD;
&#xD;
             16. Subject is able to swallow pills.&#xD;
&#xD;
             Exclusion Criteria:&#xD;
&#xD;
             1. Subject is seropositive for or has active viral infection with hepatitis B virus&#xD;
             (HBV):&#xD;
&#xD;
               1. HBV surface antigen (HBsAg) positive&#xD;
&#xD;
               2. HBV surface antigen (HBsAg) negative, HBV surface ant ibody (ant i-HBs) posit ive&#xD;
                  and/or HBV core antibody (ant i-HBc) positive, and detectable viral DNA Subjects&#xD;
                  who are seropositive because of prior HBV vaccination are eligible (anti- HBs&#xD;
                  positive, anti-HBc negative, and HBsAg negative).&#xD;
&#xD;
             2. Subject is known to be seropositive for, or have an active infection with,&#xD;
             hepatitis C virus (HCV).&#xD;
&#xD;
             3. Subject is known to be seropositive for, or have an active infection with, human&#xD;
             immunodeficiency virus (HIV).&#xD;
&#xD;
             4. Subject has any neuropathy &gt; Grade 1. 5. Subject has impaired cardiac function or&#xD;
             clinically significant cardiac diseases, including any of the following:&#xD;
&#xD;
               1. Left ventricular ejection fraction (LVEF) &lt; 45% as determined by multi-gated&#xD;
                  acquisition scan (MUGA) or echocardiogram (ECHO).&#xD;
&#xD;
               2. Complete left bundle branch or bifascicular block.&#xD;
&#xD;
               3. Persistent or clinically meaningful ventricular arrhythmias.&#xD;
&#xD;
               4. Unstable angina pectoris or myocardial infarction ≤ 3 months prior to starting&#xD;
                  treatment in the study.&#xD;
&#xD;
               5. Troponin-T value &gt; 0.4 ng/mL or B-type natriuretic protein (BNP) &gt; 300 pg/mL by&#xD;
                  central laboratory assessment Subjects with baseline troponin-T &gt; ULN or BNP &gt;&#xD;
                  100 pg/mL are eligible but must have a cardiologist evaluation prior to&#xD;
                  enrollment in the trial for baseline assessment and optimization of&#xD;
                  cardioprotective therapy.&#xD;
&#xD;
                  If troponin-T is not usually tested by local laboratory then troponin-I may be&#xD;
                  used to confirm subject meets the Screening eligibility criteria. The central&#xD;
                  laboratory sample must still be collected prior to first dose and sent to central&#xD;
                  laboratory. Elevated cut-off value for troponin I will depend on the assay used&#xD;
                  at the site. If baseline troponin I &gt;ULN, the subject must have a cardiologist&#xD;
                  consultation prior to enrollment and optimization of cardioprotective therapy.&#xD;
&#xD;
                  In case of discrepancy between both troponin-I and troponin-T test, the&#xD;
                  troponin-T test will be repeated.&#xD;
&#xD;
               6. Subject has confirmed central nervous system (CNS) involvement by DLBCL. Subjects&#xD;
                  at risk for CNS involvement per Investigator assessment must receive prophylaxis.&#xD;
                  For subjects at risk, or with any neurological symptoms, testing for CNS&#xD;
                  involvement is required at Screening.&#xD;
&#xD;
               7. Subject has any significant medical condition, laboratory abnormality, or&#xD;
                  psychiatric illness that would prevent the subject from participating in the&#xD;
                  study.&#xD;
&#xD;
               8. Subject has any condition including the presence of laboratory abnormalities,&#xD;
                  which places the subject at unacceptable risk if he/she were to participate in&#xD;
                  the study.&#xD;
&#xD;
               9. Subject has any condition that confounds the ability to interpret data from the&#xD;
                  study.&#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>Richard Delarue, MD</last_name>
    <role>Study Director</role>
    <affiliation>Celgene</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>George Washington University</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20037</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Moffitt Cancer Center</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Gent</name>
      <address>
        <city>Gent</city>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Gasthuisberg</name>
      <address>
        <city>Lueven</city>
        <zip>B-3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tom Baker Cancer Center</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N 4N2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Princess Margaret Cancer Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jewish General Hospital</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3T 1E2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Germans Trias I Pujol</name>
      <address>
        <city>Badalona</city>
        <zip>8916</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <zip>8035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de San Pedro de Alcantara</name>
      <address>
        <city>Caceres</city>
        <zip>10003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Fundacion Jimenez Diaz</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario 12 de Octubre</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinico Universitario de Salamanca</name>
      <address>
        <city>Salamanca</city>
        <zip>37007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen Del Rocio</name>
      <address>
        <city>Sevilla</city>
        <zip>41013</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Canada</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>September 6, 2017</study_first_submitted>
  <study_first_submitted_qc>September 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 14, 2017</study_first_posted>
  <last_update_submitted>April 28, 2021</last_update_submitted>
  <last_update_submitted_qc>April 28, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 29, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Diffuse B-Cell Lymphoma</keyword>
  <keyword>R-CHOP-21</keyword>
  <keyword>International Prognostic Index (IPI)</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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prednisone</mesh_term>
    <mesh_term>Prednisolone</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Rituximab</mesh_term>
    <mesh_term>Vincristine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03283202
org study id: CC-122-DLBCL-002
secondary id: U1111-1201-1994
secondary id: 2016-003778-42
nct id: NCT03283202
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is Phase 1/2 study of avadomide (CC-122) in combination with rituximab,
      cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy, for
      first-line treatment of patients with Diffuse B-Cell Large B-Cell Lymphoma (DLBCL) that has
      poor risk factors. Approximately 40% of patients diagnosed with DLBCL are not cured with
      R-CHOP alone and would need additional treatment for DLBCL in the future. The addition of the
      experimental drug avadomide (CC-122) with R-CHOP could help in controlling DLBCL in this
      patient population.
This research study is for patients who have been newly diagnosed with diffuse large B-cell
      lymphoma DLBCL and are receiving treatment for the first time.

      This study will be conducted in two phases. Phase 1 will test the safety of increasing dose
      levels of avadomide (CC-122) when given in combination with R-CHOP-21 therapy to identify an
      appropriate dose and schedule for further evaluation in Phase 2. Phase 2 will evaluate the
      rate of complete response when adding avadomide (CC-122) to the R-CHOP-21 regimen in
      first-line treatment of patients with poor risk DLBCL.

      This study is separated into three periods: the Screening period, the Treatment period and
      the Follow-up period. Before the patient can receive the drug the doctor will perform test to
      find out whether he/she can participate in the study. This is done during the Screening
      period. If the patient and the treating physician determine that the patient is eligible to
      participate in the study, the patient will be registered in the study and receive avadomide
      (CC-122) combined with R-CHOP.

      In the Treatment period the patient will receive treatment for up to 6 treatment cycles. Each
      treatment cycle is 21 days long. The full length of the treatment period will be
      approximately 4 months.

      The follow-up period begins when the patient has completed treatment or is discontinued for
      any reason. During the follow-up period the patient will have fewer exams, test and visits.
      The first follow-up visit will be 28 days after treatment is completed or discontinued. After
      that, the follow-up visits will be every 3 months during the first year, then every 6 months
      until the study is closed.

      Upon completion of the Phase 1 portion of the study, a decision not to proceed with the Phase
      2 portion was taken by the Sponsor. The decision to terminate the study after Phase 1 was not
      based on any safety concerns that posed an unacceptable risk for this patient population and
      no safety issues have been identified
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose/Maximum Administered Dose (MTD/MAD) (Phase 1)
time frame: Through 6 cycles of treatment (approximately 18 weeks or 4 months)
description: Frequency of dose-limiting toxicities (DLTs) associated with the addition of avadomide (CC-122) to R-CHOP-21 therapy
measure: Complete Response Rate (CRR); Percentage of participants experiencing positron emission tomography (PET)-negative complete response (CR) (Phase 2)
time frame: 6 to 8 weeks after completion of treatment
description: CR is defined as target nodes/nodal masses regress to ≤ 1.5 cm in LDi; no extralymphatic sites of disease; no measurable lesions, no organ enlargement and normal morphology on bone marrow (BM) exam; immunohistochemically (IHC) negative
measure: Overall Response Rate (ORR); Percentage of participants who achieve a PR or CR according to the Lugano criteria.
time frame: 6 to 8 weeks after completion of treatment
description: ORR is defined as the rate of the responses (including CR; see definition above for CR and PR; PR is defined as ≥ 50% decrease in sum of perpendicular diameters (SPD) of up to 6 target measurable nodes and extranodal sites. When a lesion is too small to measure on CT, assign 5 mm × 5 mm as the default value; When no longer visible, 0 × 0 mm; for a node > 5 mm × 5 mm, but smaller than normal, use actual measurement for calculation; Absent/normal, regressed, but no increase in non measurable lesions; spleen must have regressed > 50% in length beyond normal and no new lesions.
measure: ORR by Predictive Gene Signature
time frame: 6 to 8 weeks after completion of treatment
description: ORR by Predictive Gene Signature is defined as the correlation between baseline gene expression signatures and clinical response to study treatment
measure: Progression-free Survival (PFS)
time frame: From enrollment up to 24 months after last subject is enrolled
description: PFS is defined as the time from enrollment to disease progression or death from any cause
measure: Event-free Survival (EFS)
time frame: At 12 and 24 months after enrollment
description: EFS is defined as the percentage of participants without event (relapse or progression, unplanned re-treatment of lymphoma after initial immunochemotherapy, or death from any cause)
measure: Overall Survival (OS)
time frame: Up to 24 months after enrollment
description: OS is defined as the time from enrollment until death from any cause
measure: Adverse Events (AEs)
time frame: From enrollment until at least 28 days after completion of 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 pre- existing condition) should be considered an AE.
arm group label: Avadomide (CC-122) plus R-CHOP-21
arm group type: Experimental
description: Avadomide (CC-122) by mouth (PO) at varying dose levels (Ph 1) on Days 1 through 5 and Days 8 through 12 plus Rituxan 375 mg/m2 by intravenous (IV) infusion, cyclophosphamide 750mg/m2 by IV infusion, doxorubicin 50 mg/m2 IV, vincristine 1.4 mg/m2 (max is 2.0 mg) IV and 100 mg PO prednisone/prednisolone on Days 1 through 5 of each 21-day treatment cycles for up to 6 total treatment cycles (approximately 18 weeks or 4 months)
intervention type: Drug
intervention name: Avadomide (CC-122)
description: Avadomide (CC-122) by mouth at the assigned dose in Ph 1 starting on Day 1 for 5 consecutive days per week, followed by 2 days without avadomide (CC-122) administration (5/7) for the first two weeks of a 21-day treatment cycle. If the highest proposed dose level to be explored in Phase 1 is applied, the dosing regimen will be 5/7 days for all 3 weeks of each 21-day treatment cycle.
arm group label: Avadomide (CC-122) plus R-CHOP-21
intervention type: Drug
intervention name: Rituximab
description: Rituxan 375 mg/m2 on Day 1 by intravenous (IV) infusion of a 21-day treatment cycle for up to a total of 6 cycles
arm group label: Avadomide (CC-122) plus R-CHOP-21
other name: Rituxan, MabThera
intervention type: Drug
intervention name: Cyclophosphamide 750mg/m2 by IV infusion
description: Cyclophosphamide 750mg/m2 on Day 1 by IV infusion of a 21-day treatment cycle for up to a total of 6 cycles
arm group label: Avadomide (CC-122) plus R-CHOP-21
intervention type: Drug
intervention name: Vincristine
description: Vincristine 1.4 mg/m2 (maximum of 2.0 mg total) on Day 1 by IV bolus on Day 1 of a 21-day treatment cycle for up to a total of 6 cycles
arm group label: Avadomide (CC-122) plus R-CHOP-21
other name: Oncovin, Vincasar
intervention type: Drug
intervention name: Prednisone
description: Prednisone 100 mg PO on Days 1 through 5 of each 21-day treatment or 100mg IV on Day 1 is also acceptable for up to a total of 6 cycles
arm group label: Avadomide (CC-122) plus R-CHOP-21
other name: Prednisolone
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Richard Delarue, MD
role: Study Director
affiliation: Celgene
facility: 
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country: Belgium
country: Canada
country: Spain
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, B-Cell
mesh term: Prednisone
mesh term: Prednisolone
mesh term: Cyclophosphamide
mesh term: Rituximab
mesh term: Vincristine
sharing ipd: Undecided