<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/NCT03793140</url>
  </required_header>
  <id_info>
    <org_study_id>18-443</org_study_id>
    <nct_id>NCT03793140</nct_id>
  </id_info>
  <brief_title>A Study of CPI-613 for Patients With Relapsed or Refractory Burkitt Lymphoma/Leukemia or High-Grade B-Cell Lymphoma With High-Risk Translocations</brief_title>
  <official_title>A Phase II Clinical Trial of CPI-613 in Patients With Relapsed or Refractory Burkitt Lymphoma/Leukemia or High-grade B-cell Lymphoma With Rearrangements of MYC and BCL2 and/or BCL6</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Memorial Sloan Kettering Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>City of Hope Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>George Washington University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Memorial Sloan Kettering Cancer Center</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to test any good and bad effects of the study drug, CPI-613.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 31, 2018</start_date>
  <completion_date type="Anticipated">December 2024</completion_date>
  <primary_completion_date type="Anticipated">December 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>This is an open-label multicenter, single-arm, phase II trial of CPI-613 monotherapy.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>overall response rate of CPI-613</measure>
    <time_frame>3 years</time_frame>
    <description>ORR will be defined as rate of complete response (CR) + partial response (PR) + minor response (MR) + Stable disease (SD) as determined as per the RECIL criteria. RECIL criteria for response assessment in lymphoma and/or bone marrow biopsy (depending on sites of disease as indicated by treating physician).</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">34</enrollment>
  <condition>Lymphoma</condition>
  <condition>Leukemia</condition>
  <arm_group>
    <arm_group_label>CPI-613</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>CPI-613 IV induction (Days 1-5 for first 2 Cycles [14-day cycles]), followed by CPI-613 IV maintenance (Days 1-5 for all Cycles thereafter [21-day cycles].</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CPI-613</intervention_name>
    <description>CPI-613 [2,500 mg/m2/day IV] over 2 hours (+/- 10 mins) Induction tx: Cycle 1 and 2: Treatment on Days 1-5 (Each cycle is 14 days). (Each Cycle is 14 days) Maintenance tx: All subsequent Cycles: Treatment with CPI-613 [2,500 mg/m2/day IV] over 2 hours (+/- 10 mins) on Days 1-5 (Each Cycle is 21 days)</description>
    <arm_group_label>CPI-613</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Must be ≥ 12 years of age.&#xD;
&#xD;
          -  Histologic diagnosis of Burkitt Lymphoma/Leukemia or high-grade B-cell lymphoma with&#xD;
             rearrangements of MYC and BCL2 and/or BCL6 confirmed at enrolling institution or&#xD;
             plasmablastic lymphoma or high-grade B-cell lymphoma with rearrangements of MYC&#xD;
             without bcl-2&#xD;
&#xD;
          -  Failure of at least one previous line of therapy.&#xD;
&#xD;
          -  Failure after prior bone marrow transplant, or ineligible for or opted not to&#xD;
             participate in bone marrow transplantation for Burkitt Lymphoma/Leukemia, or DHL/THL.&#xD;
&#xD;
          -  ECOG Performance Status of ≤ 3.&#xD;
&#xD;
               1. For patients less than 16 years of age, Lansky score ≥ 30&#xD;
&#xD;
               2. For patients 16- 17 years of age, Karnofsky score ≥ 30&#xD;
&#xD;
          -  Measurable disease as defined RECIL criteria (2017) or isolated bone marrow&#xD;
             involvement.&#xD;
&#xD;
          -  Patients must have fully recovered from the acute, non-hematological, non-infectious&#xD;
             toxicities of any prior treatment with anti-cancer drugs, radiotherapy or other&#xD;
             anti-cancer modalities. Patients with persistent, non-hematologic, non-infectious&#xD;
             toxicities from prior treatment must have documented resolution to ≤ Grade 2.&#xD;
&#xD;
          -  Patients must have, or be willing and eligible to undergo placement of, a working&#xD;
             central venous access device&#xD;
&#xD;
          -  Venous access available (e.g., portacath, PICC line or equivalent).&#xD;
&#xD;
          -  Laboratory values obtained ≤ 2 weeks prior to enrollment must demonstrate adequate&#xD;
             hepatic function, renal function, and coagulation as defined below:&#xD;
&#xD;
               -  Aspartate aminotransferase (AST/SGOT) ≤ 5x upper normal limit (ULN)&#xD;
&#xD;
               -  Alanine aminotransferase (ALT/SGPT) ≤ 5x ULN&#xD;
&#xD;
               -  Total bilirubin ≤1.5x ULN (unless related to hemolysis or Gilbert's syndrome, or&#xD;
                  involvement by lymphoma; if involvement by lymphoma: total bilirubin &lt;/= 3.0 x&#xD;
                  ULN)&#xD;
&#xD;
               -  Creatinine clearance &gt;=40cc min either by 24-hour creatinine clearance or&#xD;
                  calculated from the modified Cockcroft-Gault equation (with the use of ideal body&#xD;
                  mass [IBM] instead of mass): CRCL =(140-Age) × IBM (kg) × [0.85 if female]/[(72 •&#xD;
                  serum creatinine (mg/dL)]&#xD;
&#xD;
               -  For patients less than 16 years of age, the Bedside Schwartz equation or&#xD;
                  Creatinine-Cystatin C-based CKiD equation should be used for creatinine-based GFR&#xD;
                  calculation&#xD;
&#xD;
               -  International Normalized Ratio (INR) must be &lt;1.5. Due to the occurrence of&#xD;
                  thrombocytopenia, patients should not enter with coagulopathy. Patients on&#xD;
                  anticoagulants should be on short-acting therapy (e.g. low molecular weight&#xD;
                  heparin) rather than oral anticoagulants.&#xD;
&#xD;
               -  Albumin ≥2.0 g/dL (or ≥20 g/L)&#xD;
&#xD;
          -  Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically&#xD;
             sterile) must use accepted contraceptive methods (abstinence, intrauterine device&#xD;
             [IUD], oral contraceptive or double barrier device) during the study and must have a&#xD;
             negative serum or urine pregnancy test within 2 weeks prior to treatment initiation.&#xD;
&#xD;
          -  Females must agree to abstain from breastfeeding during study participation&#xD;
&#xD;
          -  Fertile men must practice effective contraceptive methods during the study unless&#xD;
             documentation of infertility exists.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients that have received a chemotherapy regimen with stem cell support in the&#xD;
             previous 2 months.&#xD;
&#xD;
          -  Any medical condition that is clinically unstable despite present therapy (i.e.&#xD;
             uncontrolled infection).&#xD;
&#xD;
          -  Platelets &lt; 50,000/mm3 unless attributable to marrow based (either Burkitt lymphoma or&#xD;
             DHL/THL.) Note: Patients with leukemia/lymphoma in the marrow 25,000-50,000 will be&#xD;
             assessed for grade 4 thrombocytopenia unless they have platelet recovery above grade&#xD;
             3. Patients entering with platelets &lt;25,000 will only be assessed for thrombocytopenia&#xD;
             related to drug if they recover to grade 3 or higher.&#xD;
&#xD;
          -  Serious medical illness, such as significant cardiac disease (e.g. symptomatic&#xD;
             congestive heart failure, unstable angina pectoris, coronary artery disease,&#xD;
             myocardial infarction within the past 3 months, uncontrolled cardiac arrhythmia,&#xD;
             pericardial disease or New York Heart Association Class III or IV), or severe&#xD;
             debilitating pulmonary disease, that would potentially increase patient's risk for&#xD;
             toxicity.&#xD;
&#xD;
          -  Patients with active central nervous system (CNS) parenchymal disease. Patients with&#xD;
             leptomeningeal disease are allowed as long as the CSF has cleared for more than 4&#xD;
             weeks and the patient is receiving maintenance intrathecal/intra Ommaya therapy.&#xD;
&#xD;
          -  Any active uncontrolled bleeding or bleeding diathesis (e.g., active peptic ulcer&#xD;
             disease).&#xD;
&#xD;
          -  Any condition or abnormality which may, in the opinion of the investigator, compromise&#xD;
             his or her safety.&#xD;
&#xD;
          -  HIV patients with any of the following: a) uncontrolled HIV infection defined as an&#xD;
             HIV viral load &gt; 100K copies/mL, b) a documented opportunistic infection within the&#xD;
             last 90 days, c) concurrent HIV therapy with zidovudine or any strong CYP3A4 inhibitor&#xD;
             (e.g. ritonavir or cobicistat) within 7 days of study drug due to potential drug-drug&#xD;
             interaction.&#xD;
&#xD;
          -  Patients who have received radiotherapy, surgery, treatment with cytotoxic agents,&#xD;
             treatment with biologic agents, immunotherapy , or any other anti-cancer therapy for&#xD;
             any kind for cancer, or any other investigational agent for any indication, within the&#xD;
             past 2 weeks prior to initiation of CPI-613 treatment with the exclusion of radiation&#xD;
             to one area (e.g. whole brain or involved nodal site) that does not interfere with&#xD;
             response assessment in other sites. A course of steroids (up to 14 days total) prior&#xD;
             to study initiation is acceptable.&#xD;
&#xD;
          -  Psychiatric illness or social situation that would limit the patient's ability to&#xD;
             tolerate and/or comply with study requirements.&#xD;
&#xD;
          -  Prior allogeneic stem cell transplant within 2 months of study start&#xD;
&#xD;
               1. Patients with active graft-versus-host-disease are not eligible&#xD;
&#xD;
               2. Patients receiving immunosuppressive therapy for prevention of graft-versus-host&#xD;
                  disease are not eligible&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ariela Noy, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Memorial Sloan Kettering Cancer Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ariela Noy, MD</last_name>
    <phone>646-608-3727</phone>
    <email>noya@mskcc.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Anita Kumar, MD</last_name>
    <phone>212-639-2668</phone>
  </overall_contact_backup>
  <location>
    <facility>
      <name>City of Hope</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jeremy Abramson, MD</last_name>
      <phone>617-724-4000</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Basking Ridge</name>
      <address>
        <city>Basking Ridge</city>
        <state>New Jersey</state>
        <zip>07920</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ariela Noy, MD</last_name>
      <phone>646-608-3727</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Monmouth</name>
      <address>
        <city>Middletown</city>
        <state>New Jersey</state>
        <zip>07748</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ariela Noy, MD</last_name>
      <phone>646-608-3727</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Bergen</name>
      <address>
        <city>Montvale</city>
        <state>New Jersey</state>
        <zip>07645</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ariela Noy, MD</last_name>
      <phone>646-608-3727</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Commack</name>
      <address>
        <city>Commack</city>
        <state>New York</state>
        <zip>11725</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ariela Noy, MD</last_name>
      <phone>646-608-3727</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Westchester</name>
      <address>
        <city>Harrison</city>
        <state>New York</state>
        <zip>10604</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ariela Noy, MD</last_name>
      <phone>646-608-3727</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ariela Noy, MD</last_name>
      <phone>646-608-3727</phone>
    </contact>
    <contact_backup>
      <last_name>Anita Kumar, MD</last_name>
      <phone>212-639-2668</phone>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Nassau</name>
      <address>
        <city>Uniondale</city>
        <state>New York</state>
        <zip>11553</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ariela Noy, MD</last_name>
      <phone>646-608-3727</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania (Data Collection Only)</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sunita Nasta, MD</last_name>
      <phone>215-316-5151</phone>
    </contact>
    <contact_backup>
      <last_name>Michael McNicholas, RN</last_name>
      <phone>267-804-4081</phone>
      <email>Michael.McNicholas@pennmedicine.upenn.edu</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Md Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Raphael Steiner, MD</last_name>
    </contact>
    <contact_backup>
      <phone>713-792-6161</phone>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mskcc.org/mskcc/html/44.cfm</url>
    <description>Memorial Sloan Kettering Cancer Center</description>
  </link>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>January 2, 2019</study_first_submitted>
  <study_first_submitted_qc>January 2, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 4, 2019</study_first_posted>
  <last_update_submitted>August 31, 2023</last_update_submitted>
  <last_update_submitted_qc>August 31, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Burkitt Lymphoma/Leukemia</keyword>
  <keyword>high-grade B-cell lymphoma</keyword>
  <keyword>CPI-613</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Burkitt Lymphoma</mesh_term>
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Lymphoma, B-Cell</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made following one year after publication and for up to 36 months later. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.</ipd_description>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
  </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/NCT03793140
org study id: 18-443
nct id: NCT03793140
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to test any good and bad effects of the study drug, CPI-613.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: This is an open-label multicenter, single-arm, phase II trial of CPI-613 monotherapy.
primary purpose: Treatment
masking: None (Open Label)
measure: overall response rate of CPI-613
time frame: 3 years
description: ORR will be defined as rate of complete response (CR) + partial response (PR) + minor response (MR) + Stable disease (SD) as determined as per the RECIL criteria. RECIL criteria for response assessment in lymphoma and/or bone marrow biopsy (depending on sites of disease as indicated by treating physician).
arm group label: CPI-613
arm group type: Experimental
description: CPI-613 IV induction (Days 1-5 for first 2 Cycles [14-day cycles]), followed by CPI-613 IV maintenance (Days 1-5 for all Cycles thereafter [21-day cycles].
intervention type: Drug
intervention name: CPI-613
description: CPI-613 [2,500 mg/m2/day IV] over 2 hours (+/- 10 mins) Induction tx: Cycle 1 and 2: Treatment on Days 1-5 (Each cycle is 14 days). (Each Cycle is 14 days) Maintenance tx: All subsequent Cycles: Treatment with CPI-613 [2,500 mg/m2/day IV] over 2 hours (+/- 10 mins) on Days 1-5 (Each Cycle is 21 days)
arm group label: CPI-613
criteria: 
gender: All
minimum age: 12 Years
maximum age: N/A
healthy volunteers: No
last name: Ariela Noy, MD
role: Principal Investigator
affiliation: Memorial Sloan Kettering Cancer Center
last name: Ariela Noy, MD
phone: 646-608-3727
email: noya@mskcc.org
last name: Anita Kumar, MD
phone: 212-639-2668
facility: 
status: Active, not recruiting
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
country: United States
url: http://www.mskcc.org/mskcc/html/44.cfm
description: Memorial Sloan Kettering Cancer Center
responsible party type: Sponsor
mesh term: Burkitt Lymphoma
mesh term: Lymphoma
mesh term: Leukemia
mesh term: Lymphoma, B-Cell
sharing ipd: Yes
ipd description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made following one year after publication and for up to 36 months later. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)