<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/NCT03259503</url>
  </required_header>
  <id_info>
    <org_study_id>2017-0073</org_study_id>
    <secondary_id>NCI-2018-01094</secondary_id>
    <secondary_id>2017-0073</secondary_id>
    <nct_id>NCT03259503</nct_id>
  </id_info>
  <brief_title>Olaparib and High-Dose Chemotherapy in Treating Patients With Relapsed or Refractory Lymphomas Undergoing Stem Cell Transplant</brief_title>
  <official_title>Olaparib Combined With High-Dose Chemotherapy for Refractory Lymphomas</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>M.D. Anderson Cancer Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase I trial studies the side effects and best dose of olaparib when given together&#xD;
      with high-dose chemotherapy in treating patients with lymphomas that have come back or does&#xD;
      not treatment and are undergoing stem cell transplant. Drugs used in chemotherapy, such as&#xD;
      olaparib, vorinostat, gemcitabine, busulfan, and melphalan, work in different ways to stop&#xD;
      the growth of cancer cells, either by killing the cells, by stopping them from dividing, or&#xD;
      by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as rituximab,&#xD;
      may help the body's immune system attack the cancer, and may interfere with the ability of&#xD;
      tumor cells to grow and spread. Giving olaparib and high-dose chemotherapy together may work&#xD;
      better in treating patients with relapsed/refractory lymphomas undergoing stem cell&#xD;
      transplant than with chemotherapy alone.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. Establish the maximum tolerated dose (MTD) of olaparib combined with&#xD;
      vorinostat/gemcitabine/busulfan/melphalan with autologous stem-cell transplant [ASCT]).&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Determine the 2-year event-free survival (EFS). II. 2-year overall survival (OS). III.&#xD;
      Complete remission (CR) rate. IV. Overall remission rate (ORR). V. Describe the toxicity&#xD;
      profile. VI. Describe changes of deoxyribonucleic acid (DNA) damage response and repair,&#xD;
      poly(ADP-ribose) polymerase (PARP) inhibition and downstream cellular effects in peripheral&#xD;
      blood mononuclear cells and, when available, malignant lymphocytes obtained by fine needle&#xD;
      aspiration (FNA) of peripheral lymph nodes.&#xD;
&#xD;
      OUTLINE: This is a dose-escalation study of olaparib.&#xD;
&#xD;
      Patients receive olaparib orally (PO) twice daily (BID) on days -11 to -3, vorinostat PO on&#xD;
      days -10 to -3, gemcitabine intravenously (IV) over 4.5 hours on days -9 and -4, busulfan IV&#xD;
      over 3 hours on day -9 to -6, melphalan IV over 30 minutes on days -4 and -3, and undergo&#xD;
      peripheral blood stem cell transplant IV over 30-60 minutes on day 0. Patients with CD20+&#xD;
      tumors also receive rituximab IV over 3-6 hours on day -10.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 1-2 days for 30 days and&#xD;
      then every 2 weeks for up to 100 days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 13, 2019</start_date>
  <completion_date type="Anticipated">July 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">July 31, 2024</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Dose limiting toxicities (DLT)</measure>
    <time_frame>Up to 30 days</time_frame>
    <description>All adverse events will be tabulated by dose, and a Bayesian DLT curve will be fit.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>At 2 years</time_frame>
    <description>OS will be estimated by the method of Kaplan and Meier. Participants without an event at the analysis time point (2 years) will be censored.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Event-free survival (EFS)</measure>
    <time_frame>At 2 years</time_frame>
    <description>EFS will be estimated by the method of Kaplan and Meier. Patients without an event at the analysis time point (2 years) will be censored. EFS is the time to relapse, secondary hematological malignancy, death, whichever occurred first, or last follow-up.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response (OR)</measure>
    <time_frame>Up to 100 days</time_frame>
    <description>OR will be tabulated by dose, and a Bayesian DLT curve will be fit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complete response (CR)</measure>
    <time_frame>At 100 days</time_frame>
    <description>CR will be tabulated by dose, and a Bayesian DLT curve will be fit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events</measure>
    <time_frame>At 2 years</time_frame>
    <description>All adverse events will be tabulated by dose, and a Bayesian DLT curve will be fit.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Recurrent Diffuse Large B-Cell Lymphoma</condition>
  <condition>Recurrent T-Cell Non-Hodgkin Lymphoma</condition>
  <condition>Refractory Diffuse Large B-Cell Lymphoma</condition>
  <condition>Refractory Hodgkin Lymphoma</condition>
  <condition>Refractory T-Cell Non-Hodgkin Lymphoma</condition>
  <arm_group>
    <arm_group_label>Treatment (olaparib, high-dose chemotherapy, transplant)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive olaparib PO BID on days -11 to -3, vorinostat PO on days -10 to -3, gemcitabine IV over 4.5 hours on days -9 and -4, busulfan IV over 3 hours on day -9 to -6, melphalan IV over 30 minutes on days -4 and -3, and undergo peripheral blood stem cell transplant IV over 30-60 minutes on day 0. Patients with CD20+ tumors also receive rituximab IV over 3-6 hours on day -10.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Busulfan</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (olaparib, high-dose chemotherapy, transplant)</arm_group_label>
    <other_name>1, 4-Bis[methanesulfonoxy]butane</other_name>
    <other_name>BUS</other_name>
    <other_name>Bussulfam</other_name>
    <other_name>Busulfanum</other_name>
    <other_name>Busulfex</other_name>
    <other_name>Busulphan</other_name>
    <other_name>CB 2041</other_name>
    <other_name>CB-2041</other_name>
    <other_name>Glyzophrol</other_name>
    <other_name>GT 41</other_name>
    <other_name>GT-41</other_name>
    <other_name>Joacamine</other_name>
    <other_name>Methanesulfonic Acid Tetramethylene Ester</other_name>
    <other_name>Methanesulfonic acid, tetramethylene ester</other_name>
    <other_name>Mielucin</other_name>
    <other_name>Misulban</other_name>
    <other_name>Misulfan</other_name>
    <other_name>Mitosan</other_name>
    <other_name>Myeleukon</other_name>
    <other_name>Myeloleukon</other_name>
    <other_name>Myelosan</other_name>
    <other_name>Mylecytan</other_name>
    <other_name>Myleran</other_name>
    <other_name>Sulfabutin</other_name>
    <other_name>Tetramethylene Bis(methanesulfonate)</other_name>
    <other_name>Tetramethylene bis[methanesulfonate]</other_name>
    <other_name>WR-19508</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemcitabine</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (olaparib, high-dose chemotherapy, transplant)</arm_group_label>
    <other_name>dFdC</other_name>
    <other_name>dFdCyd</other_name>
    <other_name>Difluorodeoxycytidine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Melphalan</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (olaparib, high-dose chemotherapy, transplant)</arm_group_label>
    <other_name>Alanine Nitrogen Mustard</other_name>
    <other_name>CB-3025</other_name>
    <other_name>L-PAM</other_name>
    <other_name>L-Phenylalanine Mustard</other_name>
    <other_name>L-sarcolysin</other_name>
    <other_name>L-Sarcolysin Phenylalanine mustard</other_name>
    <other_name>L-Sarcolysine</other_name>
    <other_name>Melphalanum</other_name>
    <other_name>Phenylalanine Mustard</other_name>
    <other_name>Phenylalanine nitrogen mustard</other_name>
    <other_name>Sarcoclorin</other_name>
    <other_name>Sarkolysin</other_name>
    <other_name>WR-19813</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Olaparib</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (olaparib, high-dose chemotherapy, transplant)</arm_group_label>
    <other_name>AZD 2281</other_name>
    <other_name>AZD-2281</other_name>
    <other_name>AZD2281</other_name>
    <other_name>KU-0059436</other_name>
    <other_name>Lynparza</other_name>
    <other_name>PARP Inhibitor AZD2281</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Peripheral Blood Stem Cell Transplantation</intervention_name>
    <description>Undergo peripheral blood stem cell transplant</description>
    <arm_group_label>Treatment (olaparib, high-dose chemotherapy, transplant)</arm_group_label>
    <other_name>PBPC transplantation</other_name>
    <other_name>PBSCT</other_name>
    <other_name>Peripheral Blood Progenitor Cell Transplantation</other_name>
    <other_name>Peripheral Stem Cell Support</other_name>
    <other_name>Peripheral Stem Cell Transplant</other_name>
    <other_name>Peripheral Stem Cell Transplantation</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Pharmacokinetic Study</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (olaparib, high-dose chemotherapy, transplant)</arm_group_label>
    <other_name>PHARMACOKINETIC</other_name>
    <other_name>PK Study</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Rituximab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (olaparib, high-dose chemotherapy, transplant)</arm_group_label>
    <other_name>ABP 798</other_name>
    <other_name>BI 695500</other_name>
    <other_name>C2B8 Monoclonal Antibody</other_name>
    <other_name>Chimeric Anti-CD20 Antibody</other_name>
    <other_name>CT-P10</other_name>
    <other_name>IDEC-102</other_name>
    <other_name>IDEC-C2B8</other_name>
    <other_name>IDEC-C2B8 Monoclonal Antibody</other_name>
    <other_name>MabThera</other_name>
    <other_name>Monoclonal Antibody IDEC-C2B8</other_name>
    <other_name>PF-05280586</other_name>
    <other_name>Rituxan</other_name>
    <other_name>Rituximab ABBS</other_name>
    <other_name>Rituximab Biosimilar ABP 798</other_name>
    <other_name>Rituximab Biosimilar BI 695500</other_name>
    <other_name>Rituximab Biosimilar CT-P10</other_name>
    <other_name>Rituximab Biosimilar GB241</other_name>
    <other_name>Rituximab Biosimilar IBI301</other_name>
    <other_name>Rituximab Biosimilar JHL1101</other_name>
    <other_name>Rituximab Biosimilar PF-05280586</other_name>
    <other_name>Rituximab Biosimilar RTXM83</other_name>
    <other_name>Rituximab Biosimilar SAIT101</other_name>
    <other_name>rituximab biosimilar TQB2303</other_name>
    <other_name>rituximab-abbs</other_name>
    <other_name>RTXM83</other_name>
    <other_name>Truxima</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vorinostat</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (olaparib, high-dose chemotherapy, transplant)</arm_group_label>
    <other_name>L-001079038</other_name>
    <other_name>MSK-390</other_name>
    <other_name>SAHA</other_name>
    <other_name>Suberanilohydroxamic Acid</other_name>
    <other_name>Suberoylanilide Hydroxamic Acid</other_name>
    <other_name>Zolinza</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 18-65&#xD;
&#xD;
          2. Patients with:&#xD;
&#xD;
             2.1 Diffuse large B-cell lymphoma (DLBCL) with one of the following: 2.1.1 Primary&#xD;
             refractory (no CR to 1st line) 2.1.2 High-risk relapse, defined as any of the&#xD;
             following: CR1 &lt;6 mo, secondary IPI &gt;1, or LDH &gt; 225 U/L. 2.1.3 Refractory relapse: No&#xD;
             response to &gt;/= 1 salvage line and not eligible to receive other novel salvage&#xD;
             therapies, such as CAR-T in a timely fashion or have already failed these.&#xD;
&#xD;
             2.2 Hodgkin's with one of the following: 2.2.1 Primary refractory (no CR or PD within&#xD;
             3 months) 2.2.2 High-risk relapse, defined as any of the following: CR1 &lt;1 year,&#xD;
             extranodal relapse, or B symptoms.&#xD;
&#xD;
             2.2.3 Refractory relapse: No response to &gt;/= 1 salvage line 2.3 T-non Hodgkin's&#xD;
             lymphoma (T-NHL) with one of the following: 2.3.1 Primary refractory (no CR to 1st&#xD;
             line) 2.3.2 High-risk relapse (within 6 months) 2.3.3 Refractory relapse to &gt;/= 1 line&#xD;
             of salvage 2.3.4 Any other lymphoma that is refractory or relapsed and that does not&#xD;
             qualify for autologous transplant protocols of higher priority.&#xD;
&#xD;
          3. Adequate renal function (creatinine clearance estimated using the Cockcroft-Gault&#xD;
             equation of &gt;/= 51 mL/min: Estimated creatinine clearance = (140-age [years]) x weight&#xD;
             (kg) (xF)a / serum creatinine (mg/dL) x 72 [a where F=0.85 for females and F=1 for&#xD;
             males.]&#xD;
&#xD;
          4. Adequate hepatic function (Aspartate aminotransferase (AST) (Serum Glutamic&#xD;
             Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic&#xD;
             Pyruvate Transaminase (SGPT)) &lt;/= 3.5 x institutional upper limit of normal unless&#xD;
             liver metastases or a systemic inflammatory picture secondary to the lymphoma are&#xD;
             present in which case they must be &lt;/= 6x ULN; total bilirubin &lt;/= 2.5 x ULN or &lt;/=&#xD;
             3.5 x ULN if Gilbert's disease)&#xD;
&#xD;
          5. Prothrombin time (PT) &lt;/=1.5 x institutional upper limit of normal&#xD;
&#xD;
          6. Adequate pulmonary function (FEV1, FVC and DLCOc &gt;/= 50% of predicted)&#xD;
&#xD;
          7. Adequate cardiac function (LVEF &gt;/= 40%, no uncontrolled arrhythmias or symptomatic&#xD;
             cardiac disease&#xD;
&#xD;
          8. ECOG performance status &lt;2&#xD;
&#xD;
          9. Provision of informed consent prior to any study specific procedures&#xD;
&#xD;
         10. Patients must have a life expectancy &gt;/= 16 weeks&#xD;
&#xD;
         11. Postmenopausal or evidence of non-childbearing status for women of childbearing&#xD;
             potential: negative urine or serum pregnancy test within 28 days and within 72 hours&#xD;
             of study treatment and confirmed prior to receiving treatment on this study. Patients&#xD;
             with positive results will be removed from the study. Postmenopausal is defined as one&#xD;
             of the following:&#xD;
&#xD;
             11.1 Amenorrheic for 1 year or more following cessation of exogenous hormonal&#xD;
             treatments.&#xD;
&#xD;
             11.2 Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the&#xD;
             postmenopausal range for women under 50.&#xD;
&#xD;
             11.3 Radiation-induced oophorectomy with last menses &gt;1 year ago. 11.4&#xD;
             Chemotherapy-induced menopause with &gt;1 year interval since last menses. 11.5 Surgical&#xD;
             sterilization (bilateral oophorectomy or hysterectomy). 11.6 Female patients must&#xD;
             agree to use a highly effective birth control method while on study and for at least 6&#xD;
             months after the last dose of study drug(s).&#xD;
&#xD;
         12. Male patients and their partners, who are sexually active and of childbearing&#xD;
             potential, must agree to the use of two highly effective forms of contraception in&#xD;
             combination, throughout the period of taking study treatment and for 6 months after&#xD;
             last dose of study drug(s) to prevent pregnancy in a partner.&#xD;
&#xD;
         13. Patient is willing and able to comply with the protocol for the duration of the study&#xD;
             including undergoing treatment and scheduled visits and examinations.&#xD;
&#xD;
         14. Prior apheresis of &gt;/= 3 million CD34+ cells/Kg.&#xD;
&#xD;
        Eligibility for ASCT is determined by the above inclusion criteria 3-7.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Persistent toxicities (&gt;Common Terminology Criteria for Adverse Event (CTCAE) grade 2)&#xD;
             caused by previous cancer therapy, excluding alopecia.&#xD;
&#xD;
          2. Prior whole brain irradiation&#xD;
&#xD;
          3. Active hepatitis B, either active carrier (HBsAg +) or viremic (HBV DNA &gt;/= 10,000&#xD;
             copies/mL, or &gt;/= 2,000 IU/mL)&#xD;
&#xD;
          4. Evidence of either cirrhosis or stage 3-4 liver fibrosis in patients with chronic&#xD;
             hepatitis C or positive hepatitis C serology&#xD;
&#xD;
          5. Active infection requiring parenteral antibiotics&#xD;
&#xD;
          6. Patients who are known to be serologically positive for human immunodeficiency virus&#xD;
             (HIV).&#xD;
&#xD;
          7. Patients receiving any systemic chemotherapy or radiotherapy (except for palliative&#xD;
             reasons) within 3 weeks prior to study treatment&#xD;
&#xD;
          8. Pregnancy&#xD;
&#xD;
          9. Other malignancy within the last 5 years except: adequately treated non-melanoma skin&#xD;
             cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ&#xD;
             (DCIS), Stage 1, grade 1 endometrial carcinoma, or other solid tumors.&#xD;
&#xD;
         10. Resting ECG with QTcF &gt; 470 msec on 2 or more time points within a 24 hour period or&#xD;
             family history of long QT syndrome.&#xD;
&#xD;
         11. Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin,&#xD;
             clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir,&#xD;
             saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg.&#xD;
             ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout&#xD;
             period prior to starting olaparib is 2 weeks.&#xD;
&#xD;
         12. Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin,&#xD;
             rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort ) or&#xD;
             moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout&#xD;
             period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3&#xD;
             weeks for other agents.&#xD;
&#xD;
         13. Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features&#xD;
             suggestive of MDS/AML.&#xD;
&#xD;
         14. Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence&#xD;
             of brain metastases is not required. The patient can receive a stable dose of&#xD;
             corticosteroids before and during the study as long as these were started at least 4&#xD;
             weeks prior to treatment. Patients with spinal cord compression unless considered to&#xD;
             have received definitive treatment for this and evidence of clinically stable disease&#xD;
             for 28 days.&#xD;
&#xD;
         15. Major surgery within 2 weeks of starting study treatment and patients must have&#xD;
             recovered from any effects of any major surgery.&#xD;
&#xD;
         16. Uncontrolled non-malignant systemic disease or active, uncontrolled infection.&#xD;
             Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent&#xD;
             (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable&#xD;
             spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral&#xD;
             lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric&#xD;
             disorder that prohibits obtaining informed consent.&#xD;
&#xD;
         17. Patients unable to swallow orally administered medication and patients with&#xD;
             gastrointestinal disorders likely to interfere with absorption of the study&#xD;
             medication.&#xD;
&#xD;
         18. Breast feeding women.&#xD;
&#xD;
         19. Patients with a known hypersensitivity to olaparib or any of the excipients of the&#xD;
             product.&#xD;
&#xD;
         20. Medical, psychiatric, cognitive or other conditions that compromise the patient's&#xD;
             ability to understand the patient information, to give informed consent, to comply&#xD;
             with the study protocol or to complete the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yago L Nieto</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>M D Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mdanderson.org</url>
    <description>MD Anderson Cancer Center</description>
  </link>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>August 22, 2017</study_first_submitted>
  <study_first_submitted_qc>August 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 23, 2017</study_first_posted>
  <last_update_submitted>August 29, 2023</last_update_submitted>
  <last_update_submitted_qc>August 29, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 31, 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</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
    <mesh_term>Lymphoma, B-Cell</mesh_term>
    <mesh_term>Lymphoma, Large B-Cell, Diffuse</mesh_term>
    <mesh_term>Lymphoma, T-Cell</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rituximab</mesh_term>
    <mesh_term>Antineoplastic Agents, Immunological</mesh_term>
    <mesh_term>Gemcitabine</mesh_term>
    <mesh_term>Melphalan</mesh_term>
    <mesh_term>Busulfan</mesh_term>
    <mesh_term>Olaparib</mesh_term>
    <mesh_term>Mechlorethamine</mesh_term>
    <mesh_term>Vorinostat</mesh_term>
    <mesh_term>Nitrogen Mustard Compounds</mesh_term>
    <mesh_term>Antibodies</mesh_term>
    <mesh_term>Immunoglobulins</mesh_term>
    <mesh_term>Antibodies, Monoclonal</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/NCT03259503
org study id: 2017-0073
secondary id: NCI-2018-01094
secondary id: 2017-0073
nct id: NCT03259503
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This phase I trial studies the side effects and best dose of olaparib when given together
      with high-dose chemotherapy in treating patients with lymphomas that have come back or does
      not treatment and are undergoing stem cell transplant. Drugs used in chemotherapy, such as
      olaparib, vorinostat, gemcitabine, busulfan, and melphalan, work in different ways to stop
      the growth of cancer cells, either by killing the cells, by stopping them from dividing, or
      by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as rituximab,
      may help the body's immune system attack the cancer, and may interfere with the ability of
      tumor cells to grow and spread. Giving olaparib and high-dose chemotherapy together may work
      better in treating patients with relapsed/refractory lymphomas undergoing stem cell
      transplant than with chemotherapy alone.
PRIMARY OBJECTIVE:

      I. Establish the maximum tolerated dose (MTD) of olaparib combined with
      vorinostat/gemcitabine/busulfan/melphalan with autologous stem-cell transplant [ASCT]).

      SECONDARY OBJECTIVES:

      I. Determine the 2-year event-free survival (EFS). II. 2-year overall survival (OS). III.
      Complete remission (CR) rate. IV. Overall remission rate (ORR). V. Describe the toxicity
      profile. VI. Describe changes of deoxyribonucleic acid (DNA) damage response and repair,
      poly(ADP-ribose) polymerase (PARP) inhibition and downstream cellular effects in peripheral
      blood mononuclear cells and, when available, malignant lymphocytes obtained by fine needle
      aspiration (FNA) of peripheral lymph nodes.

      OUTLINE: This is a dose-escalation study of olaparib.

      Patients receive olaparib orally (PO) twice daily (BID) on days -11 to -3, vorinostat PO on
      days -10 to -3, gemcitabine intravenously (IV) over 4.5 hours on days -9 and -4, busulfan IV
      over 3 hours on day -9 to -6, melphalan IV over 30 minutes on days -4 and -3, and undergo
      peripheral blood stem cell transplant IV over 30-60 minutes on day 0. Patients with CD20+
      tumors also receive rituximab IV over 3-6 hours on day -10.

      After completion of study treatment, patients are followed up every 1-2 days for 30 days and
      then every 2 weeks for up to 100 days.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Dose limiting toxicities (DLT)
time frame: Up to 30 days
description: All adverse events will be tabulated by dose, and a Bayesian DLT curve will be fit.
measure: Overall survival (OS)
time frame: At 2 years
description: OS will be estimated by the method of Kaplan and Meier. Participants without an event at the analysis time point (2 years) will be censored.
measure: Event-free survival (EFS)
time frame: At 2 years
description: EFS will be estimated by the method of Kaplan and Meier. Patients without an event at the analysis time point (2 years) will be censored. EFS is the time to relapse, secondary hematological malignancy, death, whichever occurred first, or last follow-up.
measure: Objective response (OR)
time frame: Up to 100 days
description: OR will be tabulated by dose, and a Bayesian DLT curve will be fit.
measure: Complete response (CR)
time frame: At 100 days
description: CR will be tabulated by dose, and a Bayesian DLT curve will be fit.
measure: Incidence of adverse events
time frame: At 2 years
description: All adverse events will be tabulated by dose, and a Bayesian DLT curve will be fit.
arm group label: Treatment (olaparib, high-dose chemotherapy, transplant)
arm group type: Experimental
description: Patients receive olaparib PO BID on days -11 to -3, vorinostat PO on days -10 to -3, gemcitabine IV over 4.5 hours on days -9 and -4, busulfan IV over 3 hours on day -9 to -6, melphalan IV over 30 minutes on days -4 and -3, and undergo peripheral blood stem cell transplant IV over 30-60 minutes on day 0. Patients with CD20+ tumors also receive rituximab IV over 3-6 hours on day -10.
intervention type: Drug
intervention name: Busulfan
description: Given IV
arm group label: Treatment (olaparib, high-dose chemotherapy, transplant)
other name: 1, 4-Bis[methanesulfonoxy]butane
other name: BUS
other name: Bussulfam
other name: Busulfanum
other name: Busulfex
other name: Busulphan
other name: CB 2041
other name: CB-2041
other name: Glyzophrol
other name: GT 41
other name: GT-41
other name: Joacamine
other name: Methanesulfonic Acid Tetramethylene Ester
other name: Methanesulfonic acid, tetramethylene ester
other name: Mielucin
other name: Misulban
other name: Misulfan
other name: Mitosan
other name: Myeleukon
other name: Myeloleukon
other name: Myelosan
other name: Mylecytan
other name: Myleran
other name: Sulfabutin
other name: Tetramethylene Bis(methanesulfonate)
other name: Tetramethylene bis[methanesulfonate]
other name: WR-19508
intervention type: Drug
intervention name: Gemcitabine
description: Given IV
arm group label: Treatment (olaparib, high-dose chemotherapy, transplant)
other name: dFdC
other name: dFdCyd
other name: Difluorodeoxycytidine
intervention type: Drug
intervention name: Melphalan
description: Given IV
arm group label: Treatment (olaparib, high-dose chemotherapy, transplant)
other name: Alanine Nitrogen Mustard
other name: CB-3025
other name: L-PAM
other name: L-Phenylalanine Mustard
other name: L-sarcolysin
other name: L-Sarcolysin Phenylalanine mustard
other name: L-Sarcolysine
other name: Melphalanum
other name: Phenylalanine Mustard
other name: Phenylalanine nitrogen mustard
other name: Sarcoclorin
other name: Sarkolysin
other name: WR-19813
intervention type: Drug
intervention name: Olaparib
description: Given PO
arm group label: Treatment (olaparib, high-dose chemotherapy, transplant)
other name: AZD 2281
other name: AZD-2281
other name: AZD2281
other name: KU-0059436
other name: Lynparza
other name: PARP Inhibitor AZD2281
intervention type: Procedure
intervention name: Peripheral Blood Stem Cell Transplantation
description: Undergo peripheral blood stem cell transplant
arm group label: Treatment (olaparib, high-dose chemotherapy, transplant)
other name: PBPC transplantation
other name: PBSCT
other name: Peripheral Blood Progenitor Cell Transplantation
other name: Peripheral Stem Cell Support
other name: Peripheral Stem Cell Transplant
other name: Peripheral Stem Cell Transplantation
intervention type: Other
intervention name: Pharmacokinetic Study
description: Correlative studies
arm group label: Treatment (olaparib, high-dose chemotherapy, transplant)
other name: PHARMACOKINETIC
other name: PK Study
intervention type: Biological
intervention name: Rituximab
description: Given IV
arm group label: Treatment (olaparib, high-dose chemotherapy, transplant)
other name: ABP 798
other name: BI 695500
other name: C2B8 Monoclonal Antibody
other name: Chimeric Anti-CD20 Antibody
other name: CT-P10
other name: IDEC-102
other name: IDEC-C2B8
other name: IDEC-C2B8 Monoclonal Antibody
other name: MabThera
other name: Monoclonal Antibody IDEC-C2B8
other name: PF-05280586
other name: Rituxan
other name: Rituximab ABBS
other name: Rituximab Biosimilar ABP 798
other name: Rituximab Biosimilar BI 695500
other name: Rituximab Biosimilar CT-P10
other name: Rituximab Biosimilar GB241
other name: Rituximab Biosimilar IBI301
other name: Rituximab Biosimilar JHL1101
other name: Rituximab Biosimilar PF-05280586
other name: Rituximab Biosimilar RTXM83
other name: Rituximab Biosimilar SAIT101
other name: rituximab biosimilar TQB2303
other name: rituximab-abbs
other name: RTXM83
other name: Truxima
intervention type: Drug
intervention name: Vorinostat
description: Given PO
arm group label: Treatment (olaparib, high-dose chemotherapy, transplant)
other name: L-001079038
other name: MSK-390
other name: SAHA
other name: Suberanilohydroxamic Acid
other name: Suberoylanilide Hydroxamic Acid
other name: Zolinza
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Yago L Nieto
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
facility: 
country: United States
url: http://www.mdanderson.org
description: MD Anderson Cancer Center
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, Non-Hodgkin
mesh term: Lymphoma, B-Cell
mesh term: Lymphoma, Large B-Cell, Diffuse
mesh term: Lymphoma, T-Cell
mesh term: Recurrence
mesh term: Rituximab
mesh term: Antineoplastic Agents, Immunological
mesh term: Gemcitabine
mesh term: Melphalan
mesh term: Busulfan
mesh term: Olaparib
mesh term: Mechlorethamine
mesh term: Vorinostat
mesh term: Nitrogen Mustard Compounds
mesh term: Antibodies
mesh term: Immunoglobulins
mesh term: Antibodies, Monoclonal