xml: <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/NCT06003179</url>
    </required_header>
    <id_info>
      <org_study_id>OZM-123</org_study_id>
      <nct_id>NCT06003179</nct_id>
    </id_info>
    <brief_title>Optimizing Lymphodepletion to Improve Outcomes in Patients Receiving Cell Therapy With Kymriah</brief_title>
    <acronym>LOKI</acronym>
    <official_title>Optimizing Lymphodepletion to Improve Outcomes in Patients Receiving Anti-CD19 CAR T Cell Therapy With Kymriah/tIsagenlecleucel (LOKI)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University Health Network, Toronto</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University Health Network, Toronto</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This is a Phase 1b study of participants with Diffuse Large B Cell Lymphoma (DLBCL). The&#xD;
        purpose of this study is to identify an optimized lymphodenpletion (LD) regimen by evaluating&#xD;
        standard and intermediate doses of Fludarabine (Flu) / Cyclophosphamide (Cy) with or without&#xD;
        a fixed dose of total lymphoid irradiation (TLI) in the setting of standard of care CAR T&#xD;
        cell therapy.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 2023</start_date>
    <completion_date type="Anticipated">August 2028</completion_date>
    <primary_completion_date type="Anticipated">August 2026</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <intervention_model_description>Patients will be enrolled in two stages: the dose escalation stage to assess the safety and tolerability of a modified LD regimen, and once the maximum tolerated dose (MTD) is determined, a cohort expansion phase to further characterize the toxicity and efficacy profile and determine the recommended phase 2 dose (RP2D). The study will enroll approximately 20-40 patients in the dose escalation stage (Part 1), and approximately 20 further patients at cohort expansion (Part 2).</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>MTD and dose limiting toxicity (DLT) for chemo plus radiation as lymphodepletion</measure>
      <time_frame>baseline through end of study completion, approximately 2 years</time_frame>
      <description>(LD) regimen (Fludarabine (Flu)/Cyclophosphamide (Cy) + total lymphoid irradiation (TLI ) in patients receiving standard of care CAR T cell therapy for relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL) by establishing the maximum tolerated doses (MTD) of standard (JULIET) dose Flu/Cy + TLI, and of intermediate dose iCy/Flu +/- TLI and the dose limiting toxicities (DLT) of standard dose Flu/Cy + TLI, and of intermediate dose iCy/Flu +/- TLI</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>overall response rate (ORR) at 12 months of chemo rads</measure>
      <time_frame>baseline to 12 months post CAR-T</time_frame>
      <description>To assess the ORR at 12 months of a combination chemo-radiation LD regimen (standard dose Flu/Cy + TLI) in patients receiving CAR T cell therapy for R/R DLBCL.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>complete response (CR) rate at 12 months of chemo rads</measure>
      <time_frame>baseline to 12 months post CAR-T</time_frame>
      <description>To assess the CR rate of a combination chemo-radiation LD regimen (standard dose Flu/Cy + TLI) in patients receiving CAR T cell therapy for R/R DLBCL.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>progression free survival (PFS) at 12 months of chemo rads</measure>
      <time_frame>baseline to 12 months post CAR-T</time_frame>
      <description>To assess the PFS rate at 12 months of a combination chemo-radiation LD regimen (standard dose Flu/Cy + TLI) in patients receiving CAR T cell therapy for R/R DLBCL.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>ORR at 12 months of an intermediate dose iCy/Flu +/- TLI LD regimen</measure>
      <time_frame>baseline to 12 months post CAR-T</time_frame>
      <description>To assess the ORR at 12 months of an intermediate dose iCy/Flu +/- TLI LD regimen in patients receiving CAR T cell therapy for R/R DLBCL</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>CR rate at 12 months of an intermediate dose iCy/Flu +/- TLI LD regimen</measure>
      <time_frame>baseline to 12 months post CAR-T</time_frame>
      <description>To assess the CR rate at 12 months of an intermediate dose iCy/Flu +/- TLI LD regimen in patients receiving CAR T cell therapy for R/R DLBCL</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PFS at 12 months of an intermediate dose iCy/Flu +/- TLI LD regimen</measure>
      <time_frame>baseline to 12 months post CAR-T</time_frame>
      <description>To assess the PFS rate at 12 months of an intermediate dose iCy/Flu +/- TLI LD regimen in patients receiving CAR T cell therapy for R/R DLBCL</description>
    </secondary_outcome>
    <number_of_arms>6</number_of_arms>
    <enrollment type="Anticipated">40</enrollment>
    <condition>Lymphoma, Large B-Cell, Diffuse</condition>
    <arm_group>
      <arm_group_label>Cyclophosphamide and fludarabine, standard dose</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Fludarabine 25mg/m2 Cyclophosphamide 250mg/m2 Days -4, -3, -2</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cyclophosphamide and fludarabine, standard dose with radiation</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Fludarabine 25mg/m2 Cyclophosphamide 250mg/m2 Days -6, -5, -4 2 Gy in 2 Fractions Days -3, -2</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cyclophosphamide (intermediate dose) and fludarabine</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Fludarabine 25mg/m2 Cyclophosphamide 500mg/m2 Days -4, -3, -2</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cyclophosphamide (intermediate dose) and fludarabine with radiation</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Fludarabine 25mg/m2 Cyclophosphamide 500mg/m2 Days -6, -5, -4 2 Gy in 2 Fractions Days -3, -2</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cyclophosphamide (high dose) and fludarabine</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Fludarabine 25mg/m2 Cyclophosphamide 750mg/m2 Days -4, -3, -2</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cyclophosphamide (high dose) and fludarabine with radiation</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Fludarabine 25mg/m2 Cyclophosphamide 750mg/m2 Days -6, -5, -4 2 Gy in 2 Fractions Days -3, -2</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Cyclophosphamide</intervention_name>
      <description>Conditioning chemo at different doses</description>
      <arm_group_label>Cyclophosphamide (high dose) and fludarabine</arm_group_label>
      <arm_group_label>Cyclophosphamide (high dose) and fludarabine with radiation</arm_group_label>
      <arm_group_label>Cyclophosphamide (intermediate dose) and fludarabine</arm_group_label>
      <arm_group_label>Cyclophosphamide (intermediate dose) and fludarabine with radiation</arm_group_label>
      <arm_group_label>Cyclophosphamide and fludarabine, standard dose</arm_group_label>
      <other_name>Cytoxan, neosar</other_name>
    </intervention>
    <intervention>
      <intervention_type>Radiation</intervention_type>
      <intervention_name>TLI</intervention_name>
      <description>radiation given with conditioning chemo</description>
      <arm_group_label>Cyclophosphamide (high dose) and fludarabine with radiation</arm_group_label>
      <arm_group_label>Cyclophosphamide (intermediate dose) and fludarabine with radiation</arm_group_label>
      <arm_group_label>Cyclophosphamide and fludarabine, standard dose with radiation</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Fludarabine</intervention_name>
      <description>Fludarabine given as part of standard treatment</description>
      <arm_group_label>Cyclophosphamide (high dose) and fludarabine</arm_group_label>
      <arm_group_label>Cyclophosphamide (high dose) and fludarabine with radiation</arm_group_label>
      <arm_group_label>Cyclophosphamide (intermediate dose) and fludarabine</arm_group_label>
      <arm_group_label>Cyclophosphamide (intermediate dose) and fludarabine with radiation</arm_group_label>
      <arm_group_label>Cyclophosphamide and fludarabine, standard dose</arm_group_label>
      <arm_group_label>Cyclophosphamide and fludarabine, standard dose with radiation</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Age ≥ 18 years at the time of informed consent&#xD;
  &#xD;
            2. Life expectancy ≥ 12 weeks&#xD;
  &#xD;
            3. Biopsy-proven and histologically confirmed R/R large B cell lymphoma, including PMBCL,&#xD;
               R/R DLBCL and transformation from FL.&#xD;
  &#xD;
            4. Radiographically documented measurable disease as per Lugano response criteria (i.e.&#xD;
               LDi &gt; 1.5 cm that is FDG avid).&#xD;
  &#xD;
            5. At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any&#xD;
               prior systemic cancer therapy at the time the subject provides consent&#xD;
  &#xD;
            6. Eligible for standard of care CAR T cell therapy, specifically, relapsed or refractory&#xD;
               large B cell lymphoma after two or more lines of systemic therapy, and subjects must&#xD;
               have received adequate first-line therapy including at a minimum:&#xD;
  &#xD;
            7. Patient is sufficiently stable to facilitate planned CAR T-cell therapy (e.g. not&#xD;
               rapidly progressing on temporizing therapy, no significant compromise of vital organ&#xD;
               functions (intubation, dialysis, requiring ICU/vasopressor support)) and has good&#xD;
               performance status&#xD;
  &#xD;
            8. Patient does not have active CNS disease&#xD;
  &#xD;
            9. ECOG performance status 0 or 1 at enrollment&#xD;
  &#xD;
           10. Patient has not received prior adoptive T-cell immunotherapy&#xD;
  &#xD;
           11. Patient is not HIV positive&#xD;
  &#xD;
           12. Patient did not receive prior allogeneic stem cell transplant&#xD;
  &#xD;
           13. Adequate bone marrow, renal, hepatic, pulmonary and cardiac function&#xD;
  &#xD;
           14. Females of childbearing potential must have a negative serum or urine pregnancy test&#xD;
               (females who have undergone surgical sterilization or who have been postmenopausal for&#xD;
               at least 2 years are not considered to be of childbearing potential)&#xD;
  &#xD;
           15. Sexually active males who accept to use a condom during intercourse during treatment&#xD;
               and for 12 months after treatment as they should not father a child in this period. A&#xD;
               condom is required to be used also by vasectomized men (as well as during intercourse&#xD;
               with a male partner) in order to prevent delivery of the drug via seminal fluid&#xD;
  &#xD;
           16. Must have an apheresis product of non-mobilized cells accepted for manufacturing.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Persisting disease bulk (defined as ≥10 cm) on restaging imaging following bridging&#xD;
               therapy.&#xD;
  &#xD;
            2. History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g.&#xD;
               cervix, bladder, breast) unless disease free for at least 3 years&#xD;
  &#xD;
            3. History of Richter's transformation of CLL&#xD;
  &#xD;
            4. History of allogeneic stem cell transplant&#xD;
  &#xD;
            5. Received &lt; 2 lines of therapy for large B cell lymphoma&#xD;
  &#xD;
            6. Prior CD19 targeted therapy&#xD;
  &#xD;
            7. Subject has received or undergone the protocol defined treatments/therapies&#xD;
  &#xD;
            8. Prior chimeric antigen receptor therapy or other genetically modified T-cell therapy&#xD;
  &#xD;
            9. Presence of fungal, bacterial, viral, or other infection that is uncontrolled or&#xD;
               requiring intravenous (IV) antimicrobials for management. Simple urinary tract&#xD;
               infection (UTI) and uncomplicated bacterial pharyngitis are permitted if responding to&#xD;
               active treatment.&#xD;
  &#xD;
           10. Known history of infection with human immunodeficiency virus (HIV) or hepatitis B&#xD;
               (HBsAg positive) or hepatitis C virus (anti-HCV positive). If there is a positive&#xD;
               history of treated hepatitis B or hepatitis C, the viral load must be undetectable per&#xD;
               quantitative polymerase chain reaction (PCR) and/or nucleic acid testing.&#xD;
  &#xD;
           11. Active tuberculosis&#xD;
  &#xD;
           12. Subjects with detectable cerebrospinal fluid malignant cells or known CNS involvement;&#xD;
               a history of prior treated CNS lymphoma which is not active at the time of relapse is&#xD;
               permitted&#xD;
  &#xD;
           13. History or presence of significant non-malignant CNS disorder such as seizure&#xD;
               disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any&#xD;
               autoimmune disease with CNS involvement&#xD;
  &#xD;
           14. Subjects with cardiac atrial or cardiac ventricular lymphoma involvement&#xD;
  &#xD;
           15. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina,&#xD;
               New York Heart Association Class II or greater congestive heart failure, or other&#xD;
               clinically significant cardiac disease within 12 months of enrollment&#xD;
  &#xD;
           16. Requirement for urgent therapy due to tumor mass effects such as bowel obstruction or&#xD;
               blood vessel compression&#xD;
  &#xD;
           17. History of autoimmune disease, requiring systemic immunosuppression and/or systemic&#xD;
               disease modifying agents within the last 2 years.&#xD;
  &#xD;
           18. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis&#xD;
               obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active&#xD;
               pneumonitis per chest computed tomography (CT) scan at screening. History of radiation&#xD;
               pneumonitis in the radiation field (fibrosis) is allowed.&#xD;
  &#xD;
           19. History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of&#xD;
               enrollment&#xD;
  &#xD;
           20. Any medical condition likely to interfere with assessment of safety or efficacy of&#xD;
               study treatment&#xD;
  &#xD;
           21. History of severe immediate hypersensitivity reaction to tocilizumab or any of the&#xD;
               agents used in this study&#xD;
  &#xD;
           22. Treatment with a live, attenuated vaccine within 6 weeks prior to initiation of study&#xD;
               treatment, or anticipation of need for such a vaccine during the course of the study&#xD;
  &#xD;
           23. Women of childbearing potential who are pregnant or breastfeeding because of the&#xD;
               potentially dangerous effects of chemotherapy on the fetus or infant.&#xD;
  &#xD;
           24. Subjects of either sex who are not willing to practice birth control from the time of&#xD;
               consent and at least 6 months after tisagenlecleucel infusion&#xD;
  &#xD;
           25. In the investigators judgment, the subject is unlikely to complete all&#xD;
               protocol-required study visits or procedures, including follow-up visits, or comply&#xD;
               with the study requirements for participation.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 10, 2023</study_first_submitted>
    <study_first_submitted_qc>August 18, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>August 18, 2023</last_update_submitted>
    <last_update_submitted_qc>August 18, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <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>Cyclophosphamide</mesh_term>
      <mesh_term>Fludarabine</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06003179
  org study id: OZM-123
  nct id: NCT06003179
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  This is a Phase 1b study of participants with Diffuse Large B Cell Lymphoma (DLBCL). The
        purpose of this study is to identify an optimized lymphodenpletion (LD) regimen by evaluating
        standard and intermediate doses of Fludarabine (Flu) / Cyclophosphamide (Cy) with or without
        a fixed dose of total lymphoid irradiation (TLI) in the setting of standard of care CAR T
        cell therapy.
  allocation: Non-Randomized
  intervention model: Sequential Assignment
  intervention model description: Patients will be enrolled in two stages: the dose escalation stage to assess the safety and tolerability of a modified LD regimen, and once the maximum tolerated dose (MTD) is determined, a cohort expansion phase to further characterize the toxicity and efficacy profile and determine the recommended phase 2 dose (RP2D). The study will enroll approximately 20-40 patients in the dose escalation stage (Part 1), and approximately 20 further patients at cohort expansion (Part 2).
  primary purpose: Treatment
  masking: None (Open Label)
  measure: MTD and dose limiting toxicity (DLT) for chemo plus radiation as lymphodepletion
  time frame: baseline through end of study completion, approximately 2 years
  description: (LD) regimen (Fludarabine (Flu)/Cyclophosphamide (Cy) + total lymphoid irradiation (TLI ) in patients receiving standard of care CAR T cell therapy for relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL) by establishing the maximum tolerated doses (MTD) of standard (JULIET) dose Flu/Cy + TLI, and of intermediate dose iCy/Flu +/- TLI and the dose limiting toxicities (DLT) of standard dose Flu/Cy + TLI, and of intermediate dose iCy/Flu +/- TLI
  measure: overall response rate (ORR) at 12 months of chemo rads
  time frame: baseline to 12 months post CAR-T
  description: To assess the ORR at 12 months of a combination chemo-radiation LD regimen (standard dose Flu/Cy + TLI) in patients receiving CAR T cell therapy for R/R DLBCL.
  measure: complete response (CR) rate at 12 months of chemo rads
  time frame: baseline to 12 months post CAR-T
  description: To assess the CR rate of a combination chemo-radiation LD regimen (standard dose Flu/Cy + TLI) in patients receiving CAR T cell therapy for R/R DLBCL.
  measure: progression free survival (PFS) at 12 months of chemo rads
  time frame: baseline to 12 months post CAR-T
  description: To assess the PFS rate at 12 months of a combination chemo-radiation LD regimen (standard dose Flu/Cy + TLI) in patients receiving CAR T cell therapy for R/R DLBCL.
  measure: ORR at 12 months of an intermediate dose iCy/Flu +/- TLI LD regimen
  time frame: baseline to 12 months post CAR-T
  description: To assess the ORR at 12 months of an intermediate dose iCy/Flu +/- TLI LD regimen in patients receiving CAR T cell therapy for R/R DLBCL
  measure: CR rate at 12 months of an intermediate dose iCy/Flu +/- TLI LD regimen
  time frame: baseline to 12 months post CAR-T
  description: To assess the CR rate at 12 months of an intermediate dose iCy/Flu +/- TLI LD regimen in patients receiving CAR T cell therapy for R/R DLBCL
  measure: PFS at 12 months of an intermediate dose iCy/Flu +/- TLI LD regimen
  time frame: baseline to 12 months post CAR-T
  description: To assess the PFS rate at 12 months of an intermediate dose iCy/Flu +/- TLI LD regimen in patients receiving CAR T cell therapy for R/R DLBCL
  arm group label: Cyclophosphamide and fludarabine, standard dose
  arm group type: Active Comparator
  description: Fludarabine 25mg/m2 Cyclophosphamide 250mg/m2 Days -4, -3, -2
  arm group label: Cyclophosphamide and fludarabine, standard dose with radiation
  arm group type: Experimental
  description: Fludarabine 25mg/m2 Cyclophosphamide 250mg/m2 Days -6, -5, -4 2 Gy in 2 Fractions Days -3, -2
  arm group label: Cyclophosphamide (intermediate dose) and fludarabine
  arm group type: Experimental
  description: Fludarabine 25mg/m2 Cyclophosphamide 500mg/m2 Days -4, -3, -2
  arm group label: Cyclophosphamide (intermediate dose) and fludarabine with radiation
  arm group type: Experimental
  description: Fludarabine 25mg/m2 Cyclophosphamide 500mg/m2 Days -6, -5, -4 2 Gy in 2 Fractions Days -3, -2
  arm group label: Cyclophosphamide (high dose) and fludarabine
  arm group type: Experimental
  description: Fludarabine 25mg/m2 Cyclophosphamide 750mg/m2 Days -4, -3, -2
  arm group label: Cyclophosphamide (high dose) and fludarabine with radiation
  arm group type: Experimental
  description: Fludarabine 25mg/m2 Cyclophosphamide 750mg/m2 Days -6, -5, -4 2 Gy in 2 Fractions Days -3, -2
  intervention type: Drug
  intervention name: Cyclophosphamide
  description: Conditioning chemo at different doses
  arm group label: Cyclophosphamide (high dose) and fludarabine
  arm group label: Cyclophosphamide (high dose) and fludarabine with radiation
  arm group label: Cyclophosphamide (intermediate dose) and fludarabine
  arm group label: Cyclophosphamide (intermediate dose) and fludarabine with radiation
  arm group label: Cyclophosphamide and fludarabine, standard dose
  other name: Cytoxan, neosar
  intervention type: Radiation
  intervention name: TLI
  description: radiation given with conditioning chemo
  arm group label: Cyclophosphamide (high dose) and fludarabine with radiation
  arm group label: Cyclophosphamide (intermediate dose) and fludarabine with radiation
  arm group label: Cyclophosphamide and fludarabine, standard dose with radiation
  intervention type: Drug
  intervention name: Fludarabine
  description: Fludarabine given as part of standard treatment
  arm group label: Cyclophosphamide (high dose) and fludarabine
  arm group label: Cyclophosphamide (high dose) and fludarabine with radiation
  arm group label: Cyclophosphamide (intermediate dose) and fludarabine
  arm group label: Cyclophosphamide (intermediate dose) and fludarabine with radiation
  arm group label: Cyclophosphamide and fludarabine, standard dose
  arm group label: Cyclophosphamide and fludarabine, standard dose with radiation
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  responsible party type: Sponsor
  mesh term: Lymphoma, Large B-Cell, Diffuse
  mesh term: Cyclophosphamide
  mesh term: Fludarabine