<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/NCT01679119</url>
  </required_header>
  <id_info>
    <org_study_id>UCL 11/0475</org_study_id>
    <nct_id>NCT01679119</nct_id>
  </id_info>
  <brief_title>Treatment of Patients With Diffuse Large B Cell Lymphoma Who Are Not Suitable for Anthracycline Containing Chemotherapy</brief_title>
  <acronym>INCA</acronym>
  <official_title>A Randomised Phase II Trial of Inotuzumab Ozogamicin Plus Rituximab &amp; CVP (IO-R-CVP) vs Gemcitabine Plus Rituximab &amp; CVP (Gem-R-CVP) for the First Line Treatment of Patients With DLBCL Who Are Not Suitable for Anthracycline Containing Chemotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University College, London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Cancer Research UK</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University College, London</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this trial is to compare the efficacy and safety of Inotuzumab Ozogamicin in&#xD;
      combination with R-CVP with that of R-G-CVP for the treatment of Diffuse Large B Cell&#xD;
      Lymphoma (DLBCL) in a population of patients not suitable for anthracycline based&#xD;
      chemotherapy.&#xD;
&#xD;
      There is no standard of care for the treatment of this group of patients. If demonstrated to&#xD;
      be efficacious and safe to deliver this regimen will be further tested in a phase III trial&#xD;
      to determine whether this should become the standard of care amongst patients with DLBCL not&#xD;
      fit for anthracycline (R-CHOP).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The incidence of DLBCL is increasing and with an expanding elderly population, the incidence&#xD;
      will continue to rise. Given that about 40% of cases of DLBCL occur in patients aged over 70&#xD;
      and the number of co-mobilities increases with age, research to investigate the optimal&#xD;
      treatment of DLBCL in this group of patients is needed. R-CHOP remains the standard of care&#xD;
      for the majority of patients with DLBCL, anthracycline use is precluded in a proportion of&#xD;
      these patients by a high risk of developing cardiotoxicity, especially congestive cardiac&#xD;
      failure. Currently there is no standard of care for patients who are unfit for anthracycline&#xD;
      treatment. It has been routine to omit the doxorubicin from R-CHOP, giving R-CVP instead.&#xD;
      However the outcome for patients treated with R-CVP is poor and attempts have been made to&#xD;
      replace the doxorubicin with alternative agents. The trial will compare an experimental arm&#xD;
      consisting of Inotuzumab Ozogamicin added to the standard immunochemotherapy regimen of&#xD;
      rituximab, cyclophosphamide, vincristine and prednisolone (R-CVP) with the control arm of&#xD;
      gemcitabine added to the same combination (Gem-R-CVP).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2013</start_date>
  <completion_date type="Actual">March 2022</completion_date>
  <primary_completion_date type="Actual">March 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>At 2 years following date of randomisation.</time_frame>
    <description>Progression free survival rate and will be analysed using Kaplan-Meier survival analysis. PFS time will be measured from date of randomisation until progression or death.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall response rate</measure>
    <time_frame>Approximately 6 months after treatment start</time_frame>
    <description>At the end of treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>5 years from date of registration</time_frame>
    <description>Date of registration until death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment toxicity</measure>
    <time_frame>7 months from beginning of treatment</time_frame>
    <description>During treatment and follow up visits</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life of patients during and after treatment</measure>
    <time_frame>Baseline, during treatment and 6 month and 2 year follow up</time_frame>
    <description>QoL questionnaires (EORTC QLQ-C30; Quality of life of cancer patients; 30 questions) to be completed by patient at time points listed below</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Activities of Daily Living of patients during and after treatment</measure>
    <time_frame>Baseline, during treatment and 6 month and 2 year follow up</time_frame>
    <description>Activities of Daily Living questionnaire (ADL) to be completed by patient at time points listed below (6 questions about ability to undertake self-care)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Instrumental Activities of Daily Living of patients during and after treatment</measure>
    <time_frame>Baseline, during treatment and 6 month and 2 year follow up</time_frame>
    <description>Instrumental Activities of Daily Living questionnaire (IADL) to be completed by patient at time points listed below (8 questions about ability to undertake daily activities/self-care)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Performance status post treatment</measure>
    <time_frame>Baseline, every 21 days for 8 cycles, 5 1/2 months at the end of treatment and then up to 3 years after the end of treatment.</time_frame>
    <description>Performance status to be measured by investigator at time points listed below</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Co-morbidities of patients</measure>
    <time_frame>Baseline</time_frame>
    <description>Details of co-morbidities to be recorded at point of randomisation by investigator</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">129</enrollment>
  <condition>Diffuse Large B Cell Lymphoma</condition>
  <arm_group>
    <arm_group_label>IO-R-CVP</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Inotuzumab Ozogamicin plus Rituximab and CVP (Cyclophosphamide, vincristine &amp; prednisolone).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Gem-R-CVP</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Gemcitabine plus Rituximab and CVP (Cyclophosphamide, Vincristine and Prednisolone).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Cyclophosphamide 750mg/m2 IV, given day 1</description>
    <arm_group_label>Gem-R-CVP</arm_group_label>
    <arm_group_label>IO-R-CVP</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vincristine</intervention_name>
    <description>Vincristine 1.4mg/m2(max 2mg)IV given day 1</description>
    <arm_group_label>Gem-R-CVP</arm_group_label>
    <arm_group_label>IO-R-CVP</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prednisolone</intervention_name>
    <description>Prednisolone 100mg OD Oral given days 1-5</description>
    <arm_group_label>Gem-R-CVP</arm_group_label>
    <arm_group_label>IO-R-CVP</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rituximab</intervention_name>
    <description>Rituximab 375mg/m2 IV given day 1</description>
    <arm_group_label>Gem-R-CVP</arm_group_label>
    <arm_group_label>IO-R-CVP</arm_group_label>
    <other_name>MabThera</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Inotuzumab Ozogamicin</intervention_name>
    <description>Inotuzumab Ozogamicin 0.8mg/m2 IV given on day 2</description>
    <arm_group_label>IO-R-CVP</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemcitabine</intervention_name>
    <description>Gemcitabine up to 1g/m2 IV given day 1 and day 8 (Patients with ECOG PS 0-1: starting dose: 875mg/m2 (1st cycle). If tolerated can be escalated to 1g/m2 in cycle 2 and subsequent cycles. Patients with ECOG PS 2: starting dose 750mg/m2 (1st cycle). If tolerated can be escalated to 875mg/m2 in cycle 2 and then escalated to 1g/m2 in cycle 3 and subsequent cycles.)</description>
    <arm_group_label>Gem-R-CVP</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Informed written consent for the trial&#xD;
&#xD;
          -  Histologically proven diffuse large B cell lymphoma (DLBCL) according to the current&#xD;
             World Health Organisation (WHO) classification including all morphological variants.&#xD;
             The B cell nature of the proliferation must be verified by demonstration of CD20&#xD;
             positivity. A concurrent (synchronous) diagnosis of low grade lymphoma (e.g. on bone&#xD;
             marrow trephine or presence of both low grade and DLBCL in a lymph node biopsy) or&#xD;
             previous diagnosis of low grade lymphoma which hasn't been treated with a systemic&#xD;
             therapy is permitted&#xD;
&#xD;
          -  Bulky Stage IA (lymph node or lymph node mass ≥ 10cm in maximum diameter), stage IB,&#xD;
             stage II, stage III and stage IV disease&#xD;
&#xD;
          -  ECOG performance status 0-2&#xD;
&#xD;
          -  Measurable disease&#xD;
&#xD;
          -  Age 18 ≥ years&#xD;
&#xD;
          -  Adequate contraceptive precautions for all patients of childbearing potential&#xD;
&#xD;
          -  History of malignant disease diagnosed at any time in the past with completed radical&#xD;
             treatment and the risk of relapsing within the next 5 years is &lt;10%. Patients&#xD;
             previously treated should be free of sequelae of treatment which would compromise the&#xD;
             delivery of study drugs as compared with other eligible patients.&#xD;
&#xD;
          -  No previous chemotherapy, radiotherapy or other investigational drug for this&#xD;
             indication - previous corticosteroids up to a dose equivalent to prednisolone&#xD;
             1mg/kg/day for up to 14 days are permitted prior to randomisation EITHER&#xD;
&#xD;
          -  Unsuitable for anthracycline-containing chemotherapy due to impaired cardiac function&#xD;
             defined by an ejection fraction of ≤ 50% OR Left ventricle ejection fraction &gt; 50% but&#xD;
             in the presence of significant co-morbidities (diabetes mellitus, hypertension or&#xD;
             ischaemic heart disease) precluding anthracycline-containing chemotherapy as&#xD;
             determined by treating physician. Co-morbidities must be documented on the&#xD;
             randomisation form and CIRS score recorded&#xD;
&#xD;
          -  Adequate bone marrow function (Platelets &gt; 100x109/l, WBC &gt; 3.0x109/l, Neutrophils &gt;&#xD;
             1.5x109/l) at time of study entry unless attributed to bone marrow infiltration by&#xD;
             DLBCL&#xD;
&#xD;
          -  Life expectancy &gt; 3 months&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Symptomatic central nervous system or meningeal involvement by DLBCL&#xD;
&#xD;
          -  Previous diagnosis of low grade lymphoma which has been treated with a systemic&#xD;
             therapy&#xD;
&#xD;
          -  Non-bulky stage IA disease&#xD;
&#xD;
          -  ECOG performance status 3-4&#xD;
&#xD;
          -  History of chronic liver disease or suspected alcohol abuse&#xD;
&#xD;
          -  Serum bilirubin greater than upper limit of normal unless attributable to Gilberts&#xD;
             syndrome or haemolysis&#xD;
&#xD;
          -  Alanine and/or aspartate aminotransferase levels (ALT and/or AST) and alkaline&#xD;
             phosphatase (ALP) greater than 2.5 times the upper limit of normal&#xD;
&#xD;
          -  Glomerular filtration rate (GFR) &lt; 30ml/min. GFR calculated by Cockroft-Gault (not&#xD;
             eGFR).&#xD;
&#xD;
          -  Serological evidence of active hepatitis B or C infection whether acute or chronic&#xD;
             (defined as positive anti-HCV serology; positive HBsAg). All positive HBcAb results&#xD;
             should also be excluded on safety grounds regardless of HBsAg or HBV DNA status.&#xD;
             Antibodies to Hepatitis B surface antigen (anti-HBs) due to a history of past&#xD;
             vaccination is acceptable&#xD;
&#xD;
          -  Known history of HIV seropositive status&#xD;
&#xD;
          -  Patients with a history of Venoocclusive Disease (VOD) and Sinusoidal Obstructive&#xD;
             Syndrome (SOS)&#xD;
&#xD;
          -  Patients with a screening of QTcF interval &gt;470msec&#xD;
&#xD;
          -  Medical or psychiatric conditions compromising the patient's ability to give informed&#xD;
             consent&#xD;
&#xD;
          -  Women who are pregnant or lactating&#xD;
&#xD;
          -  LVEF &gt; 50% in the absence of significant co-morbidities that preclude anthracycline&#xD;
             use&#xD;
&#xD;
          -  Patients with a history of severe allergic/anaphylactic reaction to any humanised&#xD;
             monoclonal antibody&#xD;
&#xD;
          -  Patients with serious active infection&#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>Andrew McMillan</last_name>
    <role>Principal Investigator</role>
    <affiliation>Nottingham University Hospitals NHS Trust</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Stoke Mandeville Hospital (including Wycombe Hospital)</name>
      <address>
        <city>Aylesbury</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Hampshire Hospital</name>
      <address>
        <city>Basingstoke</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal United Hospital</name>
      <address>
        <city>Bath</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Bournemouth Hospital</name>
      <address>
        <city>Bournemouth</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bristol Oncology Centre</name>
      <address>
        <city>Bristol</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West Suffolk Hospital</name>
      <address>
        <city>Bury St Edmunds</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kent and Canterbury Hospital</name>
      <address>
        <city>Canterbury</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Castle Hill Hospital</name>
      <address>
        <city>Cottingham</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital, Coventry</name>
      <address>
        <city>Coventry</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Darent Valley Hospital</name>
      <address>
        <city>Dartford</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Devon &amp; Exeter Hospital</name>
      <address>
        <city>Exeter</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medway Maritime Hospital</name>
      <address>
        <city>Gillingham</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beatson West of Scotland Cancer Centre (including Gartnavel Royal Hospital)</name>
      <address>
        <city>Glasgow</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>James Paget University Hospital</name>
      <address>
        <city>Great Yarmouth</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwick Park Hospital</name>
      <address>
        <city>Harrow</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kettering General Hospital</name>
      <address>
        <city>Kettering</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St James's University Hospital</name>
      <address>
        <city>Leeds</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Leicester Royal Infirmary</name>
      <address>
        <city>Leicester</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aintree University Hospital</name>
      <address>
        <city>Liverpool</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Liverpool University Hospital</name>
      <address>
        <city>Liverpool</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Guy's Hospital (including St Thomas's Hospital)</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Free Hospital</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University College London Hospital</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Luton and Dunstable Hospital</name>
      <address>
        <city>Luton</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Christie Hospital</name>
      <address>
        <city>Manchester</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Freeman Hospital</name>
      <address>
        <city>Newcastle</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Tyneside Hosptial (including Wansbeck Hospital and Hexham General Hospital)</name>
      <address>
        <city>North Shields</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Norfolk and Norwich University Hospital</name>
      <address>
        <city>Norwich</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nottingham City Hospital</name>
      <address>
        <city>Nottingham</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Princess Royal University Hospital</name>
      <address>
        <city>Orpington</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Churchill Hospital</name>
      <address>
        <city>Oxford</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Derriford Hospital</name>
      <address>
        <city>Plymouth</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen's Hospital</name>
      <address>
        <city>Romford</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southampton General Hospital</name>
      <address>
        <city>Southampton</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kings Mill Hospital</name>
      <address>
        <city>Sutton-in-Ashfield</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Torbay Hospital</name>
      <address>
        <city>Torquay</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Cornwall Hospital</name>
      <address>
        <city>Truro</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Hampshire County Hospital</name>
      <address>
        <city>Winchester</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Worcester Royal Hospital (including Kidderminster Hospital and Alexandra Hospital)</name>
      <address>
        <city>Worcester</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wythenshawe Hospital (including Trafford General Hospital)</name>
      <address>
        <city>Wythenshawe</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>July 23, 2012</study_first_submitted>
  <study_first_submitted_qc>August 30, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 5, 2012</study_first_posted>
  <last_update_submitted>May 17, 2022</last_update_submitted>
  <last_update_submitted_qc>May 17, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 18, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Diffuse large b cell lymphoma</keyword>
  <keyword>Inotuzumab Ozogamicin</keyword>
  <keyword>Gemcitabine</keyword>
  <keyword>Rituximab</keyword>
  <keyword>Cyclophosphamide</keyword>
  <keyword>Vincristine</keyword>
  <keyword>Prednisolone</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, B-Cell</mesh_term>
    <mesh_term>Lymphoma, Large B-Cell, Diffuse</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prednisolone</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Rituximab</mesh_term>
    <mesh_term>Gemcitabine</mesh_term>
    <mesh_term>Vincristine</mesh_term>
    <mesh_term>Inotuzumab Ozogamicin</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01679119
org study id: UCL 11/0475
nct id: NCT01679119
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
The purpose of this trial is to compare the efficacy and safety of Inotuzumab Ozogamicin in
      combination with R-CVP with that of R-G-CVP for the treatment of Diffuse Large B Cell
      Lymphoma (DLBCL) in a population of patients not suitable for anthracycline based
      chemotherapy.

      There is no standard of care for the treatment of this group of patients. If demonstrated to
      be efficacious and safe to deliver this regimen will be further tested in a phase III trial
      to determine whether this should become the standard of care amongst patients with DLBCL not
      fit for anthracycline (R-CHOP).
The incidence of DLBCL is increasing and with an expanding elderly population, the incidence
      will continue to rise. Given that about 40% of cases of DLBCL occur in patients aged over 70
      and the number of co-mobilities increases with age, research to investigate the optimal
      treatment of DLBCL in this group of patients is needed. R-CHOP remains the standard of care
      for the majority of patients with DLBCL, anthracycline use is precluded in a proportion of
      these patients by a high risk of developing cardiotoxicity, especially congestive cardiac
      failure. Currently there is no standard of care for patients who are unfit for anthracycline
      treatment. It has been routine to omit the doxorubicin from R-CHOP, giving R-CVP instead.
      However the outcome for patients treated with R-CVP is poor and attempts have been made to
      replace the doxorubicin with alternative agents. The trial will compare an experimental arm
      consisting of Inotuzumab Ozogamicin added to the standard immunochemotherapy regimen of
      rituximab, cyclophosphamide, vincristine and prednisolone (R-CVP) with the control arm of
      gemcitabine added to the same combination (Gem-R-CVP).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression free survival
time frame: At 2 years following date of randomisation.
description: Progression free survival rate and will be analysed using Kaplan-Meier survival analysis. PFS time will be measured from date of randomisation until progression or death.
measure: Overall response rate
time frame: Approximately 6 months after treatment start
description: At the end of treatment
measure: Overall Survival
time frame: 5 years from date of registration
description: Date of registration until death.
measure: Treatment toxicity
time frame: 7 months from beginning of treatment
description: During treatment and follow up visits
measure: Quality of life of patients during and after treatment
time frame: Baseline, during treatment and 6 month and 2 year follow up
description: QoL questionnaires (EORTC QLQ-C30; Quality of life of cancer patients; 30 questions) to be completed by patient at time points listed below
measure: Activities of Daily Living of patients during and after treatment
time frame: Baseline, during treatment and 6 month and 2 year follow up
description: Activities of Daily Living questionnaire (ADL) to be completed by patient at time points listed below (6 questions about ability to undertake self-care)
measure: Instrumental Activities of Daily Living of patients during and after treatment
time frame: Baseline, during treatment and 6 month and 2 year follow up
description: Instrumental Activities of Daily Living questionnaire (IADL) to be completed by patient at time points listed below (8 questions about ability to undertake daily activities/self-care)
measure: Performance status post treatment
time frame: Baseline, every 21 days for 8 cycles, 5 1/2 months at the end of treatment and then up to 3 years after the end of treatment.
description: Performance status to be measured by investigator at time points listed below
measure: Co-morbidities of patients
time frame: Baseline
description: Details of co-morbidities to be recorded at point of randomisation by investigator
arm group label: IO-R-CVP
arm group type: Experimental
description: Inotuzumab Ozogamicin plus Rituximab and CVP (Cyclophosphamide, vincristine & prednisolone).
arm group label: Gem-R-CVP
arm group type: Active Comparator
description: Gemcitabine plus Rituximab and CVP (Cyclophosphamide, Vincristine and Prednisolone).
intervention type: Drug
intervention name: Cyclophosphamide
description: Cyclophosphamide 750mg/m2 IV, given day 1
arm group label: Gem-R-CVP
arm group label: IO-R-CVP
intervention type: Drug
intervention name: Vincristine
description: Vincristine 1.4mg/m2(max 2mg)IV given day 1
arm group label: Gem-R-CVP
arm group label: IO-R-CVP
intervention type: Drug
intervention name: Prednisolone
description: Prednisolone 100mg OD Oral given days 1-5
arm group label: Gem-R-CVP
arm group label: IO-R-CVP
intervention type: Drug
intervention name: Rituximab
description: Rituximab 375mg/m2 IV given day 1
arm group label: Gem-R-CVP
arm group label: IO-R-CVP
other name: MabThera
intervention type: Drug
intervention name: Inotuzumab Ozogamicin
description: Inotuzumab Ozogamicin 0.8mg/m2 IV given on day 2
arm group label: IO-R-CVP
intervention type: Drug
intervention name: Gemcitabine
description: Gemcitabine up to 1g/m2 IV given day 1 and day 8 (Patients with ECOG PS 0-1: starting dose: 875mg/m2 (1st cycle). If tolerated can be escalated to 1g/m2 in cycle 2 and subsequent cycles. Patients with ECOG PS 2: starting dose 750mg/m2 (1st cycle). If tolerated can be escalated to 875mg/m2 in cycle 2 and then escalated to 1g/m2 in cycle 3 and subsequent cycles.)
arm group label: Gem-R-CVP
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Andrew McMillan
role: Principal Investigator
affiliation: Nottingham University Hospitals NHS Trust
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country: United Kingdom
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, B-Cell
mesh term: Lymphoma, Large B-Cell, Diffuse
mesh term: Prednisolone
mesh term: Cyclophosphamide
mesh term: Rituximab
mesh term: Gemcitabine
mesh term: Vincristine
mesh term: Inotuzumab Ozogamicin