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/NCT05966233</url>
    </required_header>
    <id_info>
      <org_study_id>FIL_POLA-R-DHAP</org_study_id>
      <nct_id>NCT05966233</nct_id>
    </id_info>
    <brief_title>R-DHAP vs POLA-R-DHAP Followed by Autologous Transplant as First Salvage Treatment in Patient With Relapsed or Refractory Diffuse Large B Cell Lymphoma</brief_title>
    <acronym>FIL_POLARDHAP</acronym>
    <official_title>Phase II Randomized Clinical Trial to Evaluate the Efficacy of the Addition of Polatuzumab Vedotin to Standard Chemotherapy R-DHAP (POLA-R-DHAP) as Induction Pre-transplantation Therapy in Patients With Diffuse Large B-Cell Lymphoma Refractory/Relapsed After First Line Treatment.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Fondazione Italiana Linfomi - ETS</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Roche Pharma AG</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Fondazione Italiana Linfomi - ETS</source>
    <oversight_info>
      <has_dmc>No</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>
        Prospective, multicenter, open label, phase II randomized clinical trial in DLBCL patients&#xD;
        relapsed or refractory to first line R-chemo, aged 18-70 years and candidate to autologous&#xD;
        transplant. Patients will be randomized 1:1 to received 4 cycles of R-DHAP or R-DHAP plus&#xD;
        Polatuzumab Vedotin as induction treatment plus autologous transplant.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Prospective, multicenter, open label, phase II randomized clinical trial in DLBCL patients&#xD;
        relapsed or refractory to first line R-chemo, aged 18-70 years and candidate to autologous&#xD;
        transplant. Patients will be randomized 1:1 to received 4 cycles of R-DHAP or R-DHAP plus&#xD;
        Polatuzumab Vedotin as induction treatment.&#xD;
  &#xD;
        PET-CT scan performed after induction be centrally review for disease response. Responding&#xD;
        patients (CR) after induction will be addressed to receive Autologous Stem Cells&#xD;
        Transplantation (ASCT) consolidation as per local guidelines. Patients achieving PR can&#xD;
        proceed with ASCT or with a 3rd-line treatment, according to the physician judgment. Patients&#xD;
        in SD/PD will be diverted to salvage strategies.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">October 2028</completion_date>
    <primary_completion_date type="Anticipated">October 2028</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 (PFS)</measure>
      <time_frame>From treatment start up to 30 months (6 months treatment period and 24 months of follow-up)</time_frame>
      <description>Time between the randomization to first documentation of recurrence, progression or death from any cause</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Event-Free Survival (EFS)</measure>
      <time_frame>From treatment start up to 30 months (6 months treatment period and 24 months of follow-up)</time_frame>
      <description>Time between the randomization to any treatment failure, including disease progression, or discontinuation of treatment for any reason (e.g., disease progression, toxicity, patient preference, initiation of a new treatment without documented progression) or death from any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Complete response rate (CRR)</measure>
      <time_frame>From treatment start up to end of treatment evaluation (about 6 months)</time_frame>
      <description>CRR will be defined according to Response Criteria for NHL with PET (Lugano 2014). CRR will include only patients who achieved a CR and will be evaluated on assessed patients and on all treated patients, considering patients without a response assessment (due to any reason) as non-responders.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall response rate (ORR)</measure>
      <time_frame>From treatment start up to end of treatment evaluation (about 6 months)</time_frame>
      <description>ORR will be defined as the proportion of patients who have a partial or complete response to therapy (CR+PR).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall Survival (OS)</measure>
      <time_frame>From treatment start up to 30 months (6 months treatment period and 24 months of follow-up)</time_frame>
      <description>Time between randomization to death from any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence and severity of AEs</measure>
      <time_frame>From start to end of induction treatment evaluation (about 3 months)</time_frame>
      <description>Incidence and severity of AEs in R-DHAP vs POLA-R-DHAP according to latest CTCAE criteria during induction immunochemotherapy</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Adequate stem cells mobilization</measure>
      <time_frame>From beginning of 2nd cycle to end of induction treatment evaluation (about 2 months)</time_frame>
      <description>Adequate stem cells mobilization will be defined by the target cell harvesting of 3 x 10^6 CD34+ cells/kg</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Autologous consolidation feasibility</measure>
      <time_frame>At time of end of treatment assessment (up to 6 months from treatment begin)</time_frame>
      <description>Proportion of patients receiving autologous consolidation after POLA-R-DHAP vs R-DHAP</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">150</enrollment>
    <condition>Diffuse Large B Cell Lymphoma Refractory</condition>
    <condition>Diffuse Large B-cell Lymphoma Recurrent</condition>
    <arm_group>
      <arm_group_label>R-DHAP</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>R-DHAP x4 + autologous transplant/salvage treatment (based on centrally review response)</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Pola-R-DHAP</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Pola-R-DHAP x4 + autologous transplant/salvage treatment (based on centrally review response)</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>R-DHAP</intervention_name>
      <description>Rituximab 375 mg/m2 IV on D0 or D1&#xD;
  Dexamethasone 40 mg/day IV or PO on D1-4&#xD;
  Ara-C 2 g/m2 IV on D2 (2 doses every 12h) or D2 and D3&#xD;
  Cisplatin 100 mg/ m2 IV on D1</description>
      <arm_group_label>R-DHAP</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Pola-R-DHAP</intervention_name>
      <description>Polatuzumab Vedotin 1.8 mg/kg IV on D1&#xD;
  Rituximab 375 mg/m2 IV on D0 or D1&#xD;
  Dexamethasone 40 mg/day IV or PO on D1-4&#xD;
  Ara-C 2 g/m2 IV on D2 (2 doses every 12h) or D2 and D3&#xD;
  Cisplatin 100 mg/ m2 IV on D1</description>
      <arm_group_label>Pola-R-DHAP</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Histologically documented diagnosis of Diffuse Large B-Cell Lymphoma Not otherwise&#xD;
               specified (DLBCL-NOS) as defined in the 2022 edition of the World Health Organization&#xD;
               (WHO) classification; are also admitted documented diagnosis of:&#xD;
  &#xD;
                 -  T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL)&#xD;
  &#xD;
                 -  Epstein-barr virus (EBV)-associated DLBCL&#xD;
  &#xD;
                 -  Double-hit and triple-hit high grade B-cell lymphomas (HGBL DH/TH)&#xD;
  &#xD;
                 -  High-grade B-cell lymphoma, NOS (HGBL)&#xD;
  &#xD;
                 -  Transformed FL not previously untreated&#xD;
  &#xD;
                 -  Follicular large B-cell lymphoma (FLBL, former follicular 3b)&#xD;
  &#xD;
            2. Known availability of biopsy material (at relapse/refractory or previous most recent).&#xD;
               Re-biopsy highly encouraged even if not mandatory. Central pathology review required,&#xD;
               but not mandatory for registration and treatment start;&#xD;
  &#xD;
            3. Relapse or refractoriness after the first line R-chemo (R-CHOP o similar). Previous&#xD;
               treatment with polatuzumab containing regimen is allowed as per clinician judgment;&#xD;
  &#xD;
            4. CAR-T not indicated or unavailable;&#xD;
  &#xD;
            5. Age 18-70 years. sGA mandatory for patients 65-70 years old: only category FIT&#xD;
               admitted [20] (see Appendix A);&#xD;
  &#xD;
            6. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 if not related to&#xD;
               lymphoma disease (see Appendix B);&#xD;
  &#xD;
            7. Measurable disease ≥ 1.5 cm in longest diameter, and measurable in 2 perpendicular&#xD;
               dimensions;&#xD;
  &#xD;
            8. Normal blood count defined as: neutrophils at least 1.500/mmc, platelets at least&#xD;
               75.000/mmc, haemoglobin at least 8,0 g/dL with transfusion independence, unless&#xD;
               abnormalities due to underlying disease (bone marrow involvement), at the moment of&#xD;
               signing informed consent;&#xD;
  &#xD;
            9. Adequate liver function, assessed by baseline laboratory values; the increase to up to&#xD;
               2.5 ULN for transaminases and up to 1.5 ULN for bilirubin admitted for cases with&#xD;
               documented liver involvement by lymphoma;&#xD;
  &#xD;
           10. Adequate renal function defined as creatinine clearance ≥ 40 mL/min (Cockcroft-Gault&#xD;
               formula; see Appendix C)&#xD;
  &#xD;
           11. Subjects HBsAg negative but positive for antibodies to hepatitis B core antigen with&#xD;
               undetectable HBV-DNA measured by real-time polymerase chain reaction (PCR).&#xD;
  &#xD;
           12. Women of childbearing potential (WOCBP) and men must agree to use effective&#xD;
               contraception if sexually active. Females of childbearing potential and males with&#xD;
               female partners of reproductive potential should be advised to use effective&#xD;
               contraception while receiving polatuzumab vedotin and for 9 months after the last dose&#xD;
               of polatuzumab vedotin for female patients and for 6 months after the last dose of&#xD;
               polatuzumab vedotin for male patients with female partners of reproductive potential.&#xD;
               A woman is considered of childbearing potential, i.e. fertile, following menarche and&#xD;
               until becoming post-menopausal unless permanently sterile. Permanent sterilization&#xD;
               methods include but are not limited to hysterectomy, bilateral salpingectomy and&#xD;
               bilateral oophorectomy. A postmenopausal state is defined as no menses for continuous&#xD;
               12 months without an alternative medical cause. A high follicle stimulating hormone&#xD;
               (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state&#xD;
               in women not using hormonal contraception or hormonal replacement therapy. The&#xD;
               investigator or a designated associate is requested to advise the patient how to&#xD;
               achieve highly effective birth control method (failure rate of less than 1%) e.g.&#xD;
               intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral&#xD;
               tubal occlusion, vasectomized partner. The use of condoms by male patients is required&#xD;
               (even if surgically sterilized, i.e., status post vasectomy) unless the female partner&#xD;
               is permanently sterile. Full sexual abstinence is admitted when this is in line with&#xD;
               the preferred and usual lifestyle of the subject, for the same time period planned for&#xD;
               other methods of birth control (see above). Periodic abstinence (e.g., calendar,&#xD;
               ovulation, symptothermal, post ovulation methods for the female partner) and&#xD;
               withdrawal are not acceptable methods of contraception&#xD;
  &#xD;
           13. WOCBP must have a negative serum (beta-human chorionic gonadotropin [b-hCG]) or urine&#xD;
               pregnancy test at Screening. Women who are pregnant or breastfeeding are ineligible&#xD;
               for this study;&#xD;
  &#xD;
           14. Life expectancy &gt; 6 months;&#xD;
  &#xD;
           15. Subject understands and voluntarily signs an informed consent form approved by the&#xD;
               National Ethics Committee prior to the initiation of any screening or study-specific&#xD;
               procedures;&#xD;
  &#xD;
           16. Subject must be able to adhere to the study visit schedule and other protocol&#xD;
               requirements.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Any histology other than DLBCL&#xD;
  &#xD;
            2. Primary mediastinal lymphoma (PMBCL)&#xD;
  &#xD;
            3. Known central nervous system lymphoma&#xD;
  &#xD;
            4. Known history of severe allergic or anaphylactic reactions to human, humanized,&#xD;
               chimeric, or murine monoclonal antibodies&#xD;
  &#xD;
            5. Contraindication to any drug in the chemotherapy regimen&#xD;
  &#xD;
            6. Left ventricular ejection fraction (LVEF) &lt; 50%&#xD;
  &#xD;
            7. Neuropathy ≥ grade 2&#xD;
  &#xD;
            8. Subject is:&#xD;
  &#xD;
                 -  Seropositive for hepatitis B, defined by a positive test for hepatitis B surface&#xD;
                    antigen [HBsAg]. EXCEPTION: Subjects with serologic findings suggestive of HBV&#xD;
                    vaccination (HBsAb positivity as the only serologic marker) AND a known history&#xD;
                    of prior HBV vaccination, do not need to be tested for HBV DNA by PCR&#xD;
  &#xD;
                 -  Known to be seropositive for hepatitis C. EXCEPTION: Patients with presence of&#xD;
                    HCV antibody, but PCR negative for HCV-RNA are eligible&#xD;
  &#xD;
                 -  Positive for human immunodeficiency virus (HIV) infection&#xD;
  &#xD;
            9. Any uncontrolled active systemic infection requiring intravenous (IV) antibiotics&#xD;
  &#xD;
           10. History of stroke or intracranial hemorrhage within the past 6 months.&#xD;
  &#xD;
           11. History of clinically relevant liver or renal insufficiency; significant cardiac,&#xD;
               vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic,&#xD;
               hematologic, psychiatric, or metabolic disturbances&#xD;
  &#xD;
           12. Clinically significant cardiovascular disease&#xD;
  &#xD;
           13. Major surgical intervention prior 4 weeks to enrollment if not due to lymphoma and/or&#xD;
               other disease life-threatening that can compromise chemotherapy treatment&#xD;
  &#xD;
           14. Prior malignancies other than lymphoma in the last 5 years with exception of currently&#xD;
               treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma&#xD;
               of the cervix&#xD;
  &#xD;
           15. Any life-threatening illness, medical condition, or organ system dysfunction which, in&#xD;
               the investigator's opinion, could compromise the subject's safety&#xD;
  &#xD;
           16. If female, the patient is pregnant or breast-feeding&#xD;
  &#xD;
           17. Patients participating in other clinical studies&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>70 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Monica Balzarotti, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Dipartimento di Oncologia Medica ed Ematologia - Istituto Clinico Humanitas - Rozzano (MI)</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Uffici Studi FIL</last_name>
      <phone>+390131033153</phone>
      <email>startup@filinf.it</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Uffici Studi FIL</last_name>
      <phone>+390599769913</phone>
      <email>gestionestudi@filinf.it</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>A.O. SS. Antonio e Biagio e Cesare Arrigo, S.C. Ematologia</name>
        <address>
          <city>Alessandria</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Manuela Zanni, MD</last_name>
        <email>manuela.zanni@ospedale.al.it</email>
      </contact>
      <investigator>
        <last_name>Manuela Zanni, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>AOU Ospedali Riuniti, Clinica di Ematologia</name>
        <address>
          <city>Ancona</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Guido Gini, MD</last_name>
        <email>guido.gini@ospedaliriuniti.marche.it</email>
      </contact>
      <investigator>
        <last_name>Guido Gini, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Azienda Ospedaliera S.Giuseppe Moscati, S.C. Ematologia e Trapianto emopoietico</name>
        <address>
          <city>Avellino</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Sonya De Lorenzo, MD</last_name>
        <email>sonya.delorenzo@tin.it</email>
      </contact>
      <investigator>
        <last_name>Sonya De Lorenzo, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>IRCCS Centro di Riferimento Oncologico di Aviano, Divisione di Oncologia e dei Tumori immuto-correlati</name>
        <address>
          <city>Aviano</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Michele Spina, MD</last_name>
        <email>mspina@cro.it</email>
      </contact>
      <investigator>
        <last_name>Michele Spina, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>IRCCS Istituto Tumori Giovanni Paolo II, U.O.C Ematologia</name>
        <address>
          <city>Bari</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Giacomo Loseto, MD</last_name>
        <email>loseto.giacomo@gmail.com</email>
      </contact>
      <investigator>
        <last_name>Giacomo Loseto, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Cliniche Humanitas Gavazzeni, Oncologia</name>
        <address>
          <city>Bergamo</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Daniele Laszlo, MD</last_name>
        <email>daniele.laszlo@gavazzeni.it</email>
      </contact>
      <investigator>
        <last_name>Daniele Laszlo, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>ASST Spedali Civili di Brescia, Ematologia</name>
        <address>
          <city>Brescia</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Alessandra Tucci, MD</last_name>
        <email>alessandra.tucci@asst-spedalicivili.it</email>
      </contact>
      <investigator>
        <last_name>Alessandra Tucci, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Ospedale Businco, SC Ematologia e CTMO</name>
        <address>
          <city>Cagliari</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Sara Veronica Usai, MD</last_name>
        <email>sara.v.usai@aob.it</email>
      </contact>
      <investigator>
        <last_name>Sara Veronica Usai, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Fondazione del Piemonte per l'Oncologia - IRCCS, Ematologia</name>
        <address>
          <city>Candiolo</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Pio Manlio Mirko Frascione, MD</last_name>
        <email>piomanliomirko.frascione@ircc.it</email>
      </contact>
      <investigator>
        <last_name>Pio Manlio Mirko Frascione, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Arnas Nuovo Ospedale Garibaldi Nesima, U.O.C. Ematologia</name>
        <address>
          <city>Catania</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Ugo Consoli, MD</last_name>
        <email>ugo.consoli144@gmail.com</email>
      </contact>
      <investigator>
        <last_name>Ugo Consoli, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>A.O. S. Croce e Carle, S.C. di Ematologia e Trapianto di Midollo Osseo</name>
        <address>
          <city>Cuneo</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Claudia Castellino, MD</last_name>
        <email>castellino.c@ospedale.cuneo.it</email>
      </contact>
      <investigator>
        <last_name>Claudia Castellino, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Azienda Ospedaliera Universitaria Careggi, Unitа funzionale di Ematologia</name>
        <address>
          <city>Firenze</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Luca Nassi, MD</last_name>
        <email>nassil@aou-careggi.toscana.it</email>
      </contact>
      <investigator>
        <last_name>Luca Nassi, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Ospedale Vito Fazzi, Ematologia</name>
        <address>
          <city>Lecce</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Valentina Bozzoli, MD</last_name>
        <email>vbozzoli.ematolecce@gmail.com</email>
      </contact>
      <investigator>
        <last_name>Valentina Bozzoli, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>ASST Ovest Milanese - Legnano, U.O.C. Ematologia</name>
        <address>
          <city>Legnano</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Michela Draisci, MD</last_name>
        <email>michela.draisci@asst-ovestmi.it</email>
      </contact>
      <investigator>
        <last_name>Michela Draisci, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>ASST Grande Ospedale Metropolitano Niguarda, SC Ematologia</name>
        <address>
          <city>Milano</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Emanuele Ravano, MD</last_name>
        <email>emanuele.ravano@ospedaleniguarda.it</email>
      </contact>
      <investigator>
        <last_name>Emanuele Ravano, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Istituto Scientifico San Raffaele, Unitа Linfomi - Dipartimento Oncoematologia</name>
        <address>
          <city>Milano</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Andrés Ferreri, MD</last_name>
        <email>andres.ferreri@hsr.it</email>
      </contact>
      <investigator>
        <last_name>Andrés Ferreri, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Ospedale Maggiore Policlinico - Fondazione IRCCS Ca Granda, Ematologia</name>
        <address>
          <city>Milano</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Francesca Gaia Rossi, MD</last_name>
        <email>francescagaia.rossi@policlinico.mi.it</email>
      </contact>
      <investigator>
        <last_name>Francesca Gaia Rossi, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Fondazione IRCCS San Gerardo dei Tintori, Ematologia</name>
        <address>
          <city>Monza</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Federica Cocito, MD</last_name>
        <email>cocitofederica@gmail.com</email>
      </contact>
      <investigator>
        <last_name>Federica Cocito, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>AOU Maggiore della Caritа di Novara, SCDU Ematologia</name>
        <address>
          <city>Novara</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Riccardo Bruna</last_name>
        <email>riccardo.bruna@med.uniupo.it</email>
      </contact>
      <investigator>
        <last_name>Riccardo Bruna, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Presidio ospedaliero &quot;A. TORTORA&quot;, U.O. Onco-ematologia</name>
        <address>
          <city>Pagani</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Catello Califano, MD</last_name>
        <email>c.califano@aslsalerno.it</email>
      </contact>
      <investigator>
        <last_name>Catello Califano, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>A.O. Ospedali Riuniti Villa Sofia-Cervello, Divisione di Ematologia</name>
        <address>
          <city>Palermo</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Caterina Patti, MD</last_name>
        <email>k.patti@villasofia.it</email>
      </contact>
      <investigator>
        <last_name>Caterina Patti, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Ospedale S. Maria della Misericordia, Ematologia</name>
        <address>
          <city>Perugia</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Leonardo Flenghi, MD</last_name>
        <email>leonardo.flenghi@ospedale.perugia.it</email>
      </contact>
      <investigator>
        <last_name>Leonardo Flenghi, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>P.O. Spirito Santo di Pescara, UOS Dipartimentale - Centro di diagnosi e Terapia dei linfomi</name>
        <address>
          <city>Pescara</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Elsa Pennese, MD</last_name>
        <email>elsa.pennese@asl.pe.it</email>
      </contact>
      <investigator>
        <last_name>Elsa Pennese, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Ospedale Guglielmo da Saliceto, U.O.Ematologia</name>
        <address>
          <city>Piacenza</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Annalisa Arcari, MD</last_name>
        <email>a.arcari@ausl.pc.it</email>
      </contact>
      <investigator>
        <last_name>Annalisa Arcari, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>AOU Pisana, U.O. Ematologia</name>
        <address>
          <city>Pisa</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Sara Galimberti, MD</last_name>
        <email>sara.galimberti@med.unipi.it</email>
      </contact>
      <investigator>
        <last_name>Sara Galimberti, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>A.O.R. &quot;San Carlo&quot;, U.O. Ematologia</name>
        <address>
          <city>Potenza</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Michele Cimminiello</last_name>
        <email>miki-doc@virgilio.it</email>
      </contact>
      <investigator>
        <last_name>Michele Cimminiello, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Ospedale delle Croci, Ematologia</name>
        <address>
          <city>Ravenna</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Monica Tani, MD</last_name>
        <email>monica.tani@auslromagna.it</email>
      </contact>
      <investigator>
        <last_name>Monica Tani, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Azienda Unitа Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova, Ematologia</name>
        <address>
          <city>Reggio Emilia</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Maria Elena Nizzoli, MD</last_name>
        <email>mariaelena.nizzoli@ausl.re.it</email>
      </contact>
      <investigator>
        <last_name>Maria Elena Nizzoli, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>AO San Giovanni Addolorata, S.C. Ematologia</name>
        <address>
          <city>Roma</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Erica Finolezzi, MD</last_name>
        <email>erica.finolezzi@gmail.com</email>
      </contact>
      <investigator>
        <last_name>Erica Finolezzi, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>AO Sant Andrea, Ematologia</name>
        <address>
          <city>Roma</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Agostino Tafuri, MD</last_name>
        <email>agostino.tafuri@ospedalesantandrea.it</email>
      </contact>
      <investigator>
        <last_name>Agostino Tafuri, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Policlinico Umberto I - Universitа &quot;La Sapienza&quot;, Istituto Ematologia -Dipartimento di Medicina Traslazionale e di Precisione</name>
        <address>
          <city>Roma</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Alice Di Rocco, MD</last_name>
        <email>dirocco@bce.uniroma1.it</email>
      </contact>
      <investigator>
        <last_name>Alice Di Rocco, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Policlinico Universitario Campus Bio-Medico, Ematologia - Trapianto cellule staminali - Medicina Trasfusionale e Terapia cellulare</name>
        <address>
          <city>Roma</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Luigi Rigacci, MD</last_name>
        <email>l.rigacci@policlinicocampus.it</email>
      </contact>
      <investigator>
        <last_name>Luigi Rigacci, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Istituto Clinico Humanitas, U.O. Ematologia</name>
        <address>
          <city>Rozzano</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Monica Balzarotti, MD</last_name>
        <email>monica.balzarotti@humanitas.it</email>
      </contact>
      <investigator>
        <last_name>Monica Balzarotti, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>AOU Senese, U.O.C. Ematologia</name>
        <address>
          <city>Siena</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Alberto Fabbri, MD</last_name>
        <email>fabbri7@unisi.it</email>
      </contact>
      <investigator>
        <last_name>Alberto Fabbri, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>A.O.U. Citta della Salute e della Scienza di Torino, Ematologia Universitaria</name>
        <address>
          <city>Torino</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Federica Cavallo, MD</last_name>
        <email>f.cavallo@unito.it</email>
      </contact>
      <investigator>
        <last_name>Federica Cavallo, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>A.O.U. Citta della Salute e della Scienza di Torino, S.C.Ematologia</name>
        <address>
          <city>Torino</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Mattia Novo, MD</last_name>
        <email>mnovo@cittadellasalute.to.it</email>
      </contact>
      <investigator>
        <last_name>Mattia Novo, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Ospedale Ca Foncello, S.C di Ematologia</name>
        <address>
          <city>Treviso</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Piero Maria Stefani, MD</last_name>
        <email>pieromaria.stefani@aulss2.veneto.it</email>
      </contact>
      <investigator>
        <last_name>Piero Maria Stefani, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>A.O.C. Panico, U.O.C Ematologia e Trapianto</name>
        <address>
          <city>Tricase</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Vincenzo Pavone, MD</last_name>
        <email>salentoematologia@piafondazionepanico.it</email>
      </contact>
      <investigator>
        <last_name>Vincenzo Pavone, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), SC Ematologia</name>
        <address>
          <city>Trieste</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Francesco Zaja, MD</last_name>
        <email>francesco.zaja@asugi.sanita.fvg.it</email>
      </contact>
      <investigator>
        <last_name>Francesco Zaja, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>AOU Integrata di Verona, U.O. Ematologia</name>
        <address>
          <city>Verona</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Angelo Andreini, MD</last_name>
        <email>angelo.andreini@univr.it</email>
      </contact>
      <investigator>
        <last_name>Angelo Andreini, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Italy</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 21, 2023</study_first_submitted>
    <study_first_submitted_qc>July 21, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">July 28, 2023</study_first_posted>
    <last_update_submitted>July 28, 2023</last_update_submitted>
    <last_update_submitted_qc>July 28, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Lymphoma</keyword>
    <keyword>Diffuse Large B cell Lymphoma</keyword>
    <keyword>Immunochemotherapy</keyword>
    <keyword>DLBCL</keyword>
    <keyword>Autologous</keyword>
    <keyword>Transplant</keyword>
    <keyword>Relapsed</keyword>
    <keyword>Refractory</keyword>
    <keyword>DHAP</keyword>
    <keyword>Rituximab</keyword>
    <keyword>Polatuzumab Vedotin</keyword>
    <keyword>Randomized</keyword>
    <keyword>R-DHAP</keyword>
    <keyword>CD79</keyword>
    <keyword>PET</keyword>
    <keyword>Review</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>
    <!-- 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/NCT05966233
  org study id: FIL_POLA-R-DHAP
  nct id: NCT05966233
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Prospective, multicenter, open label, phase II randomized clinical trial in DLBCL patients
        relapsed or refractory to first line R-chemo, aged 18-70 years and candidate to autologous
        transplant. Patients will be randomized 1:1 to received 4 cycles of R-DHAP or R-DHAP plus
        Polatuzumab Vedotin as induction treatment plus autologous transplant.
  Prospective, multicenter, open label, phase II randomized clinical trial in DLBCL patients
        relapsed or refractory to first line R-chemo, aged 18-70 years and candidate to autologous
        transplant. Patients will be randomized 1:1 to received 4 cycles of R-DHAP or R-DHAP plus
        Polatuzumab Vedotin as induction treatment.
  
        PET-CT scan performed after induction be centrally review for disease response. Responding
        patients (CR) after induction will be addressed to receive Autologous Stem Cells
        Transplantation (ASCT) consolidation as per local guidelines. Patients achieving PR can
        proceed with ASCT or with a 3rd-line treatment, according to the physician judgment. Patients
        in SD/PD will be diverted to salvage strategies.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Progression free survival (PFS)
  time frame: From treatment start up to 30 months (6 months treatment period and 24 months of follow-up)
  description: Time between the randomization to first documentation of recurrence, progression or death from any cause
  measure: Event-Free Survival (EFS)
  time frame: From treatment start up to 30 months (6 months treatment period and 24 months of follow-up)
  description: Time between the randomization to any treatment failure, including disease progression, or discontinuation of treatment for any reason (e.g., disease progression, toxicity, patient preference, initiation of a new treatment without documented progression) or death from any cause.
  measure: Complete response rate (CRR)
  time frame: From treatment start up to end of treatment evaluation (about 6 months)
  description: CRR will be defined according to Response Criteria for NHL with PET (Lugano 2014). CRR will include only patients who achieved a CR and will be evaluated on assessed patients and on all treated patients, considering patients without a response assessment (due to any reason) as non-responders.
  measure: Overall response rate (ORR)
  time frame: From treatment start up to end of treatment evaluation (about 6 months)
  description: ORR will be defined as the proportion of patients who have a partial or complete response to therapy (CR+PR).
  measure: Overall Survival (OS)
  time frame: From treatment start up to 30 months (6 months treatment period and 24 months of follow-up)
  description: Time between randomization to death from any cause.
  measure: Incidence and severity of AEs
  time frame: From start to end of induction treatment evaluation (about 3 months)
  description: Incidence and severity of AEs in R-DHAP vs POLA-R-DHAP according to latest CTCAE criteria during induction immunochemotherapy
  measure: Adequate stem cells mobilization
  time frame: From beginning of 2nd cycle to end of induction treatment evaluation (about 2 months)
  description: Adequate stem cells mobilization will be defined by the target cell harvesting of 3 x 10^6 CD34+ cells/kg
  measure: Autologous consolidation feasibility
  time frame: At time of end of treatment assessment (up to 6 months from treatment begin)
  description: Proportion of patients receiving autologous consolidation after POLA-R-DHAP vs R-DHAP
  arm group label: R-DHAP
  arm group type: Active Comparator
  description: R-DHAP x4 + autologous transplant/salvage treatment (based on centrally review response)
  arm group label: Pola-R-DHAP
  arm group type: Experimental
  description: Pola-R-DHAP x4 + autologous transplant/salvage treatment (based on centrally review response)
  intervention type: Drug
  intervention name: R-DHAP
  description: Rituximab 375 mg/m2 IV on D0 or D1
  Dexamethasone 40 mg/day IV or PO on D1-4
  Ara-C 2 g/m2 IV on D2 (2 doses every 12h) or D2 and D3
  Cisplatin 100 mg/ m2 IV on D1
  arm group label: R-DHAP
  intervention type: Drug
  intervention name: Pola-R-DHAP
  description: Polatuzumab Vedotin 1.8 mg/kg IV on D1
  Rituximab 375 mg/m2 IV on D0 or D1
  Dexamethasone 40 mg/day IV or PO on D1-4
  Ara-C 2 g/m2 IV on D2 (2 doses every 12h) or D2 and D3
  Cisplatin 100 mg/ m2 IV on D1
  arm group label: Pola-R-DHAP
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 70 Years
  healthy volunteers: No
  last name: Monica Balzarotti, MD
  role: Principal Investigator
  affiliation: Dipartimento di Oncologia Medica ed Ematologia - Istituto Clinico Humanitas - Rozzano (MI)
  last name: Uffici Studi FIL
  phone: +390131033153
  email: startup@filinf.it
  last name: Uffici Studi FIL
  phone: +390599769913
  email: gestionestudi@filinf.it
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  country: Italy
  responsible party type: Sponsor
  mesh term: Lymphoma
  mesh term: Lymphoma, B-Cell
  mesh term: Lymphoma, Large B-Cell, Diffuse