<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/NCT01719835</url>
  </required_header>
  <id_info>
    <org_study_id>RMH CCR: 3549</org_study_id>
    <secondary_id>2011-004146-18</secondary_id>
    <nct_id>NCT01719835</nct_id>
  </id_info>
  <brief_title>CHOP vs GEM-P in 1st Line Treatment of T-cell Lymphoma, Multicentre Phase II Study</brief_title>
  <acronym>CHEMO-T</acronym>
  <official_title>CHEMO-T: Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone (CHOP) Versus Gemcitabine, Cisplatin and Methyl Prednisolone (GEM-P) in the First Line Treatment Of T-cell Lymphoma,a Multicentre Randomised Phase II Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Royal Marsden NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Cancer Research UK</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Royal Marsden NHS Foundation Trust</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomised, open-label phase II study comparing GEM-P chemotherapy (experimental&#xD;
      arm) with CHOP (control arm) in previously untreated T-cell lymphoma. Eligible patients will&#xD;
      be randomised 1:1 between 4-weekly GEM-P or 3-weekly CHOP chemotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background:&#xD;
&#xD;
      T-cell lymphoma is an aggressive rare subset of Non-Hodgkin lymphoma (NHL) comprising several&#xD;
      different subtypes of disease within this group. No standard first-line treatment exists for&#xD;
      T-cell lymphoma as published series are small, with heterogeneous populations and often&#xD;
      retrospective.&#xD;
&#xD;
      Protocol Synopsis, Study Period: 5 years&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      Primary:&#xD;
&#xD;
      • To compare the complete response rate of GEM-P with CHOP chemotherapy in the first line&#xD;
      treatment of patients with T-Cell Lymphoma.&#xD;
&#xD;
      Secondary:&#xD;
&#xD;
      To investigate, between both arms:&#xD;
&#xD;
        -  Rate of metabolic complete response&#xD;
&#xD;
        -  Toxicity of treatment&#xD;
&#xD;
        -  Overall survival (OS)&#xD;
&#xD;
        -  Progression Free Survival (PFS)&#xD;
&#xD;
      Exploratory:&#xD;
&#xD;
      • Investigate impact of International Prognostic Index (IPI) on the outcomes response rate,&#xD;
      PFS and OS&#xD;
&#xD;
      Study Design:&#xD;
&#xD;
      A randomised multi-centre open-label phase II study&#xD;
&#xD;
      Indication: Previously untreated T-Cell lymphoma No of Participants: 186 (93 patients in each&#xD;
      arm)&#xD;
&#xD;
      Main Eligibility Criteria:&#xD;
&#xD;
        -  Histologically proven T-cell lymphoma of the following subtypes:&#xD;
&#xD;
        -  Peripheral T-cell lymphoma NOS&#xD;
&#xD;
        -  Systemic Anaplastic large cell lymphoma (ALCL) Anaplastic lymphoma kinase (ALK) negative&#xD;
           cases only&#xD;
&#xD;
        -  Angioimmunoblastic T-cell lymphoma&#xD;
&#xD;
        -  Hepatosplenic gamma/ delta T-cell lymphoma&#xD;
&#xD;
        -  Enteropathy-associated T-cell lymphoma&#xD;
&#xD;
        -  Bulky Stage I, Stage II, III or IV&#xD;
&#xD;
        -  No prior chemotherapy regimen&#xD;
&#xD;
        -  Patients aged 18 years or over.&#xD;
&#xD;
        -  WHO performance status 0,1 or 2&#xD;
&#xD;
        -  Adequate organ function:&#xD;
&#xD;
        -  No Central Nervous System(CNS) or leptomeningeal involvement with lymphoma&#xD;
&#xD;
        -  No treatment for lymphoma within 4 weeks of commencing trial therapy&#xD;
&#xD;
        -  No known HIV, active Hepatitis B or C infection&#xD;
&#xD;
      Treatment:&#xD;
&#xD;
      CHOP: cyclophosphamide, doxorubicin, vincristine, prednisolone every 21 days. GEM-P:&#xD;
      gemcitabine, methylprednisolone, cisplatin every 28 days.&#xD;
&#xD;
      Assessment Schedule:&#xD;
&#xD;
        -  Patients will be reviewed at baseline and prior to each scheduled dose of treatment for&#xD;
           toxicity&#xD;
&#xD;
        -  Radiological tumour assessment will be done with CT scan after every 2 cycles in Arm A&#xD;
           and after cycle 1, 3 and 4 in Arm B&#xD;
&#xD;
        -  PET/CT scan will be performed at baseline and upon completion of treatment..&#xD;
&#xD;
        -  Follow up after completion of treatment will be 3, 6, 9, 12, 18, 24 months then annually&#xD;
           for 5 years in total. CT scan will be performed at 3 &amp; 12 months.&#xD;
&#xD;
        -  Following disease progression patients will be followed for survival every 3 months&#xD;
           until death&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>March 2012</start_date>
  <completion_date type="Anticipated">August 2022</completion_date>
  <primary_completion_date type="Actual">November 30, 2016</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>complete response rate (CR/CRu)</measure>
    <time_frame>approximately 20 weeks after randomisation</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Toxicity</measure>
    <time_frame>approximately 20 weeks after randomisation</time_frame>
    <description>using Common Terminology Criteria for Adverse Events (CTCAE)v4.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>1 and 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free survival</measure>
    <time_frame>1 and 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Metabolic Complete Response Rate</measure>
    <time_frame>approximately 20 weeks after randomisation</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">87</enrollment>
  <condition>Peripheral T-cell Lymphoma NOS</condition>
  <condition>Anaplastic Large Cell Lymphoma, ALK-Negative</condition>
  <condition>Angioimmunoblastic T-cell Lymphoma</condition>
  <condition>Hepatosplenic Gamma/ Delta T-cell Lymphoma</condition>
  <condition>Enteropathy-Associated T-Cell Lymphoma</condition>
  <arm_group>
    <arm_group_label>Chemotherapy GEM-P</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Gemcitabine, Methylprednisolone, Cisplatin</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Chemotherapy CHOP</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>750mg/m2 IV every 21 days</description>
    <arm_group_label>Chemotherapy CHOP</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemcitabine</intervention_name>
    <description>1000mg/m2 IV Days 1, 8, 15 every 28 days</description>
    <arm_group_label>Chemotherapy GEM-P</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doxorubicin</intervention_name>
    <description>50mg/m2 IV every 21 days</description>
    <arm_group_label>Chemotherapy CHOP</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vincristine</intervention_name>
    <description>1.4mg/m2 (max 2mg) IV every 21 days</description>
    <arm_group_label>Chemotherapy CHOP</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prednisolone</intervention_name>
    <description>100mg PO Days 1-5 every 21 days</description>
    <arm_group_label>Chemotherapy CHOP</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>methylprednisolone</intervention_name>
    <description>1000mg oral or IV Days 1-5 every 28 days</description>
    <arm_group_label>Chemotherapy GEM-P</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>100mg/m2 IV Day 15 every 28 days</description>
    <arm_group_label>Chemotherapy GEM-P</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Previously untreated, histologically proven T-cell Lymphoma (any of the following):&#xD;
&#xD;
          -  Peripheral T-cell lymphoma Not Otherwise Specified (PTCL NOS)&#xD;
&#xD;
          -  Systemic Anaplastic large cell lymphoma (ALCL) ALK negative cases only&#xD;
&#xD;
          -  Angioimmunoblastic T-cell lymphoma&#xD;
&#xD;
          -  Hepatosplenic gamma/ delta T-cell lymphoma&#xD;
&#xD;
          -  Enteropathy-associated T-cell lymphoma (EATL)&#xD;
&#xD;
               -  Bulky stage I not being considered for reduced chemotherapy plus involved field&#xD;
                  radiotherapy or stage II, III or IV.&#xD;
&#xD;
               -  Patient is male or female, and ≥18 years of age on the day of signing informed&#xD;
                  consent.&#xD;
&#xD;
               -  WHO performance status 0, 1 or 2.&#xD;
&#xD;
               -  Cross sectional imaging from a baseline contrast enhanced CT should show at least&#xD;
                  one measurable disease site that is at least 2 cm in longest diameter and&#xD;
                  measurable in two perpendicular dimensions with or without corresponding&#xD;
                  Fluorodeoxyglucose(FDG) avid lesions.&#xD;
&#xD;
               -  Adequate cardiac function; formal assessment of left ventricular ejection&#xD;
                  fraction is only required if clinically indicated (a baseline echocardiogram&#xD;
                  should be done for patients with either hypertension, age &gt; 60 years or history&#xD;
                  of cardiac disease)&#xD;
&#xD;
               -  Adequate bone marrow function: absolute neutrophil count (ANC) ≥1.0x109/l; white&#xD;
                  blood cell count ≥ 3x109/l; platelets ≥ 100x109/l; haemoglobin (Hb) ≥ 9g/dl (can&#xD;
                  be post-transfusion), unless deemed disease related&#xD;
&#xD;
               -  Adequate renal function: calculated creatinine clearance ≥50ml/minute.&#xD;
&#xD;
               -  Adequate liver function: serum bilirubin ≤1.5x Upper limit of normal (ULN);&#xD;
                  Alanine transaminase/Aspartate transaminase (ALT/AST) ≤2.5x ULN; ALP ≤3x ULN (in&#xD;
                  the absence of liver metastases). If liver metastases are present, ALT, AST or&#xD;
                  Alkaline phosphatase (ALP) ≤5x ULN are permitted. Isolated hyperbilirubinaemia&#xD;
                  due to Gilbert's disease is acceptable&#xD;
&#xD;
               -  Female patient of childbearing potential must have a negative serum or urine&#xD;
                  β-human chorionic gonadotropin(hCG)pregnancy test at baseline.&#xD;
&#xD;
               -  Written informed consent must be obtained prior to start of study treatments.&#xD;
                  Scans and bone marrow biopsies performed within 4 weeks of commencement of&#xD;
                  therapy will be acceptable provided they have been performed according to study&#xD;
                  requirements.&#xD;
&#xD;
               -  Patient agreeable to use contraception for the period of study treatment and up&#xD;
                  to 12 months after the last dose of study drugs.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Documented or symptomatic central nervous system involvement or leptomeningeal&#xD;
             disease.&#xD;
&#xD;
          -  Patients with no measurable disease on the contrast enhanced CT scan at baseline.&#xD;
&#xD;
          -  Any other clinically significant disease or co-morbidity which may adversely affect&#xD;
             the safe delivery of treatment within this trial.&#xD;
&#xD;
          -  Any other malignancies diagnosed or treated within the last 5 years (other than&#xD;
             curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the&#xD;
             cervix).&#xD;
&#xD;
          -  Treatment with another investigational agent within 30 days of commencing study&#xD;
             treatment.&#xD;
&#xD;
          -  Known positive tests for human immunodeficiency virus (HIV) infection, hepatitis C&#xD;
             virus, acute or active hepatitis B infection.&#xD;
&#xD;
          -  Patient is pregnant or breastfeeding, or expecting to conceive or father children&#xD;
             within one year of finishing study treatment.&#xD;
&#xD;
          -  Patients with poorly controlled diabetes mellitus&#xD;
&#xD;
          -  Hypersensitivity or contraindication to any of the study drugs as stated in the&#xD;
             Summaries of product characteristics(SmPCs)for each of the study drugs. Patients with&#xD;
             previous cardiac infarct but satisfactory cardiac function may be allowed at the&#xD;
             discretion of Chief Investigator.&#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>David Cunningham, MD FRCP</last_name>
    <role>Principal Investigator</role>
    <affiliation>Royal Marsden NHS Foundation Trust</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Royal Marsden NHS Foundation Trust - London and Surrey</name>
      <address>
        <city>London</city>
        <zip>SM2 5PT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>March 2018</verification_date>
  <study_first_submitted>April 12, 2012</study_first_submitted>
  <study_first_submitted_qc>October 30, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 1, 2012</study_first_posted>
  <last_update_submitted>March 13, 2018</last_update_submitted>
  <last_update_submitted_qc>March 13, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">March 15, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>T-Cell Lymphoma</keyword>
  <keyword>Untreated</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, T-Cell</mesh_term>
    <mesh_term>Lymphoma, T-Cell, Peripheral</mesh_term>
    <mesh_term>Lymphoma, Large-Cell, Anaplastic</mesh_term>
    <mesh_term>Enteropathy-Associated T-Cell Lymphoma</mesh_term>
    <mesh_term>Immunoblastic Lymphadenopathy</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Methylprednisolone</mesh_term>
    <mesh_term>Prednisolone</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Gemcitabine</mesh_term>
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Vincristine</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/NCT01719835
org study id: RMH CCR: 3549
secondary id: 2011-004146-18
nct id: NCT01719835
lead sponsor: 
collaborator: 
has dmc: Yes
This is a randomised, open-label phase II study comparing GEM-P chemotherapy (experimental
      arm) with CHOP (control arm) in previously untreated T-cell lymphoma. Eligible patients will
      be randomised 1:1 between 4-weekly GEM-P or 3-weekly CHOP chemotherapy.
Background:

      T-cell lymphoma is an aggressive rare subset of Non-Hodgkin lymphoma (NHL) comprising several
      different subtypes of disease within this group. No standard first-line treatment exists for
      T-cell lymphoma as published series are small, with heterogeneous populations and often
      retrospective.

      Protocol Synopsis, Study Period: 5 years

      Objectives:

      Primary:

      • To compare the complete response rate of GEM-P with CHOP chemotherapy in the first line
      treatment of patients with T-Cell Lymphoma.

      Secondary:

      To investigate, between both arms:

        -  Rate of metabolic complete response

        -  Toxicity of treatment

        -  Overall survival (OS)

        -  Progression Free Survival (PFS)

      Exploratory:

      • Investigate impact of International Prognostic Index (IPI) on the outcomes response rate,
      PFS and OS

      Study Design:

      A randomised multi-centre open-label phase II study

      Indication: Previously untreated T-Cell lymphoma No of Participants: 186 (93 patients in each
      arm)

      Main Eligibility Criteria:

        -  Histologically proven T-cell lymphoma of the following subtypes:

        -  Peripheral T-cell lymphoma NOS

        -  Systemic Anaplastic large cell lymphoma (ALCL) Anaplastic lymphoma kinase (ALK) negative
           cases only

        -  Angioimmunoblastic T-cell lymphoma

        -  Hepatosplenic gamma/ delta T-cell lymphoma

        -  Enteropathy-associated T-cell lymphoma

        -  Bulky Stage I, Stage II, III or IV

        -  No prior chemotherapy regimen

        -  Patients aged 18 years or over.

        -  WHO performance status 0,1 or 2

        -  Adequate organ function:

        -  No Central Nervous System(CNS) or leptomeningeal involvement with lymphoma

        -  No treatment for lymphoma within 4 weeks of commencing trial therapy

        -  No known HIV, active Hepatitis B or C infection

      Treatment:

      CHOP: cyclophosphamide, doxorubicin, vincristine, prednisolone every 21 days. GEM-P:
      gemcitabine, methylprednisolone, cisplatin every 28 days.

      Assessment Schedule:

        -  Patients will be reviewed at baseline and prior to each scheduled dose of treatment for
           toxicity

        -  Radiological tumour assessment will be done with CT scan after every 2 cycles in Arm A
           and after cycle 1, 3 and 4 in Arm B

        -  PET/CT scan will be performed at baseline and upon completion of treatment..

        -  Follow up after completion of treatment will be 3, 6, 9, 12, 18, 24 months then annually
           for 5 years in total. CT scan will be performed at 3 & 12 months.

        -  Following disease progression patients will be followed for survival every 3 months
           until death
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: complete response rate (CR/CRu)
time frame: approximately 20 weeks after randomisation
measure: Toxicity
time frame: approximately 20 weeks after randomisation
description: using Common Terminology Criteria for Adverse Events (CTCAE)v4.0
measure: Overall Survival
time frame: 1 and 2 years
measure: Progression Free survival
time frame: 1 and 2 years
measure: Metabolic Complete Response Rate
time frame: approximately 20 weeks after randomisation
arm group label: Chemotherapy GEM-P
arm group type: Experimental
description: Gemcitabine, Methylprednisolone, Cisplatin
arm group label: Chemotherapy CHOP
arm group type: Active Comparator
description: Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone
intervention type: Drug
intervention name: Cyclophosphamide
description: 750mg/m2 IV every 21 days
arm group label: Chemotherapy CHOP
intervention type: Drug
intervention name: Gemcitabine
description: 1000mg/m2 IV Days 1, 8, 15 every 28 days
arm group label: Chemotherapy GEM-P
intervention type: Drug
intervention name: Doxorubicin
description: 50mg/m2 IV every 21 days
arm group label: Chemotherapy CHOP
intervention type: Drug
intervention name: Vincristine
description: 1.4mg/m2 (max 2mg) IV every 21 days
arm group label: Chemotherapy CHOP
intervention type: Drug
intervention name: Prednisolone
description: 100mg PO Days 1-5 every 21 days
arm group label: Chemotherapy CHOP
intervention type: Drug
intervention name: methylprednisolone
description: 1000mg oral or IV Days 1-5 every 28 days
arm group label: Chemotherapy GEM-P
intervention type: Drug
intervention name: Cisplatin
description: 100mg/m2 IV Day 15 every 28 days
arm group label: Chemotherapy GEM-P
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: David Cunningham, MD FRCP
role: Principal Investigator
affiliation: Royal Marsden NHS Foundation Trust
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, T-Cell
mesh term: Lymphoma, T-Cell, Peripheral
mesh term: Lymphoma, Large-Cell, Anaplastic
mesh term: Enteropathy-Associated T-Cell Lymphoma
mesh term: Immunoblastic Lymphadenopathy
mesh term: Methylprednisolone
mesh term: Prednisolone
mesh term: Cyclophosphamide
mesh term: Gemcitabine
mesh term: Doxorubicin
mesh term: Vincristine