<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/NCT02249429</url>
  </required_header>
  <id_info>
    <org_study_id>PQR309-002</org_study_id>
    <nct_id>NCT02249429</nct_id>
  </id_info>
  <brief_title>Open-Label, Non Randomized Phase 2 Study With Safety Run-In</brief_title>
  <official_title>Open-Label, Non Randomized Phase 2 Study With Safety Run-In Evaluating Efficacy and Safety of PQR309 in Patients With Relapsed or Refractory Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>PIQUR Therapeutics AG</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University College London Hospitals</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Churchill Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Royal Marsden NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Haifa</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Weill Medical College of Cornell University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Institut Curie</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Clinical Center, Sarajevo</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Clinical Center Kragujevac</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Clinical Center Nis, Nis</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Institute for Oncology and Radiology Serbia, Belgrade</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Clinical Centre of Republic of Srpska</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>PIQUR Therapeutics AG</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>
      The main goal of this study is to determine the Maximum Tolerated Dose (MTD) and the&#xD;
      Recommended Phase II Dose (RP2D) as well as preliminary antitumor activity of bimiralisib&#xD;
      (PQR309) administered orally, as once daily capsules continuously and on intermittent&#xD;
      schedule in patients with relapsed or refractory lymphomas.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Open-label, non-randomized, multicentre phase 2 study with a safety run-in evaluating&#xD;
      efficacy and safety of bimiralisib (PQR309) in patients with relapsed or refractory lymphoma.&#xD;
&#xD;
      The maximum tolerated dose (MTD) of bimiralisib in patients with advanced solid tumors was&#xD;
      defined as 80 mg once daily given continuously (q.d. schedule) in a previous phase 1 study.&#xD;
      The safety run-in of this study will follow a modified 3 + 3 design to evaluate the safety of&#xD;
      60 and 80 mg bimiralisib in patients with relapsed or refractory lymphoma administered p.o.&#xD;
      once daily during a DLT (dose-limiting toxicity) period of 28 days.&#xD;
&#xD;
      In the safety run-in, three patients will be treated at 60 mg bimiralisib for 28 days.&#xD;
      Enrollment and treatment of all three patients may occur simultaneously as 80 mg bimiralisib&#xD;
      p.o. qd was established as the MTD in solid tumors. Unless a DLT is observed in any of the&#xD;
      three patients during the first 28 days of treatment, the investigators and the sponsor will&#xD;
      decide to escalate the dose to 80 mg. Intermittent dosing schedules may be evaluated if,&#xD;
      based on the overall evaluation of all the clinical and PK (pharmacokinetic) data from this&#xD;
      and other studies with bimiralisib, data emerge during step 1 of the phase 2 expansion in&#xD;
      this study, indicating that daily dosing of bimiralisib is not adequately tolerated or&#xD;
      inefficacious.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 2015</start_date>
  <completion_date type="Actual">September 11, 2018</completion_date>
  <primary_completion_date type="Actual">September 11, 2018</primary_completion_date>
  <phase>Phase 2</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>Assessment of Change of Tumor Response Criteria in lymphoma patients During Treatment with PQR309 in patients with relapsed or refractory lymphoma according to Cheston Criteria (5)</measure>
    <time_frame>28 day prior to first treatment (baseline), during treatment every 8 weeks during 6 months and every 6 months afterwards up to 1 year)</time_frame>
    <description>Radiological lymphoma Evaluation (CT or other indicated according to institutional standard practice), clinical examination and bone marrow biopsy</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of serious adverse events (SAE) and severity of all adverse events (AEs)</measure>
    <time_frame>Before treatment on Day -1,-2 and during treatment on Day 1,2,8,15,22,36,50, at the end of treatment up to 1 year and 30 days after last dose</time_frame>
    <description>Continuous dosing and intermittent dosing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of pulse rate</measure>
    <time_frame>Before treatment on Day -1,-2 and during treatment on Day 1,2,8,15,22,36,50, at the end of treatment up to 1 year and 30 days after last dose</time_frame>
    <description>Continuous dosing and intermittent dosing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in blood pressure</measure>
    <time_frame>Before treatment on Day -1,-2 and during treatment on Day 1,2,8,15,22,36,50, subsequently every 4 weeks up to 1 year, at the end of treatment up to 1 year and 30 days after last dose</time_frame>
    <description>Continuous dosing and intermittent dosing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in body temperature</measure>
    <time_frame>Before treatment on Day -1,-2 and during treatment on Day 1,2,8,15,22,36,50, subsequently every 4 weeks up to 1 year, at the end of treatment up to 1 year and 30 days after last dose</time_frame>
    <description>Continuous dosing and intermittent dosing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in ECOG (Eastern Cooperative Oncology Group) Performance status</measure>
    <time_frame>Before treatment on Day -1,-2 and during treatment on Day 1,2,8,15,22,36,50, subsequently every 4 weeks up to 1 year, at the end of treatment up to 1 year and 30 days after last dose</time_frame>
    <description>Continuous dosing and intermittent dosing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in body weight</measure>
    <time_frame>Before treatment on Day -1,-2 and during treatment on Day 1,2,8,15,22,36,50, subsequently every 4 weeks up to 1 year, at the end of treatment up to 1 year and 30 days after last dose</time_frame>
    <description>Continuous dosing and intermittent dosing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in haematology</measure>
    <time_frame>Before treatment on Day -1,-2 and during treatment on Day 1,2,8,15,22,36,50, subsequently every 4 weeks up to 1 year, at the end of treatment up to 1 year and 30 days after last dose</time_frame>
    <description>Continuous dosing and intermittent dosing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in blood chemistry</measure>
    <time_frame>Before treatment on Day -1 and during treatment on Day 1,22,50, subsequently every 4 weeks up to 1 year, at the end of treatment up to 1 year</time_frame>
    <description>Continuous dosing and intermittent dosing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in ECG (electrocardiogram)</measure>
    <time_frame>Before treatment on Day -1 and during treatment on Day 1,22,50, subsequently every 4 weeks up to 1 year, at the end of treatment up to 1 year</time_frame>
    <description>Continuous dosing and intermittent dosing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of urine analysis</measure>
    <time_frame>Before treatment on Day -1 and during treatment on Day 1,22,50, subsequently every 4 weeks up to 1 year, at the end of treatment up to 1 year</time_frame>
    <description>Continuous dosing and intermittent dosing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in HbA1c</measure>
    <time_frame>Before treatment on Day -1 and during treatment on Day 1,22,50, subsequently every 4 weeks up to 1 year, at the end of treatment up to 1 year</time_frame>
    <description>Continuous dosing and intermittent dosing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in tmax</measure>
    <time_frame>During treatment on Day 1,2, 8,15 22, 50</time_frame>
    <description>Continuous dosing and intermittent dosing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Cmax</measure>
    <time_frame>During treatment on Day 1,2, 8,15 22, 50</time_frame>
    <description>Continuous dosing and intermittent dosing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in AUC 0-24</measure>
    <time_frame>During treatment on Day 1,2, 8,15 22, 50</time_frame>
    <description>Continuous dosing and intermittent dosing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in AUClast</measure>
    <time_frame>During treatment on Day 1,2, 8,15 22, 50</time_frame>
    <description>Continuous dosing and intermittent dosing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in AUC0-∞,</measure>
    <time_frame>During treatment on Day 1,2, 8,15 22, 50</time_frame>
    <description>Continuous dosing and intermittent dosing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in t1/2</measure>
    <time_frame>During treatment on Day 1,2, 8,15 22, 50</time_frame>
    <description>Continuous dosing and intermittent dosing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in RAC</measure>
    <time_frame>During treatment on Day 1,2, 8,15 22, 50</time_frame>
    <description>Continuous dosing and intermittent dosing</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in insulin/ C-Peptide/ glucose</measure>
    <time_frame>During treatment on Day 1,2, 8,15 22, 50</time_frame>
    <description>Continuous dosing and intermittent dosing</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">53</enrollment>
  <condition>Lymphoma, Malignant</condition>
  <arm_group>
    <arm_group_label>bimiralisib (PQR309)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>bimiralisib</intervention_name>
    <description>60 mg or 80 mg bimiralisib per oral (p.o.) once daily or intermittent dosing (120mg,140mg and 160mg) until unacceptable AE, disease progression, patient's request for withdrawal, investigator judgement or death - whichever comes first.</description>
    <arm_group_label>bimiralisib (PQR309)</arm_group_label>
    <other_name>PQR309</other_name>
    <other_name>PI3K Inhibitor (phosphatidylinositol 3-kinase)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically confirmed diagnosis* of relapsed or refractory lymphoma, received at&#xD;
             least two prior lines of therapy including immuno-chemotherapy. Patients with relapsed&#xD;
             Chronic Lymphoid Leukemia (CLL) are eligible if they have received one or more prior&#xD;
             lines of any approved standard therapy. * archival biopsies may be used if obtained up&#xD;
             to a year prior to enrollment; re-biopsy is strongly recommended if last biopsy was&#xD;
             obtained more than a year ago.&#xD;
&#xD;
          2. Only for patients in the Phase 2 part: At least one measurable nodal or extra-nodal&#xD;
             lesion defined as follows: Clearly measurable (i.e. well-defined boundaries) in at&#xD;
             least two perpendicular dimensions on imaging scan with &gt; 1.5 cm in longest transverse&#xD;
             diameter.&#xD;
&#xD;
          3. Age ≥ 18 years&#xD;
&#xD;
          4. Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1 (See Appendix 2).&#xD;
&#xD;
          5. Adequate organ system functions defined as:&#xD;
&#xD;
               1. Absolute neutrophil count (ANC) ≥1.0x109/l&#xD;
&#xD;
               2. Platelets ≥ 75x109/l&#xD;
&#xD;
               3. Haemoglobin ≥ 85g/L&#xD;
&#xD;
               4. Adequate hepatic function, defined as Total bilirubin ≤ 1.5 times the upper limit&#xD;
                  of normal (ULN) and Alanine aminotransferase (ALT) and aspartate aminotransferase&#xD;
                  (AST) ≤ 2.5 times ULN (or ALT/AST ≤ 5 times ULN in patients with liver&#xD;
                  involvement)&#xD;
&#xD;
               5. Adequate renal function, defined as serum creatinine ≤ 1.5 times ULN&#xD;
&#xD;
               6. Fasting glucose &lt; 7.0 mmol/L; Glycated haemoglobin (HbA1c) &lt; 6.4%&#xD;
&#xD;
          6. Ability and willingness to swallow and retain oral medication.&#xD;
&#xD;
          7. Willingness and ability to comply with the trial procedures&#xD;
&#xD;
          8. Female and male patients with reproductive potential must agree to use effective&#xD;
             contraception from screening until 90 days after discontinuation of PQR309&#xD;
&#xD;
          9. Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Any of the following conditions precludes enrollment of a patient:&#xD;
&#xD;
          1. Immunosuppression due to:&#xD;
&#xD;
               -  Allogeneic hematopoietic stem cell transplant (HSCT)&#xD;
&#xD;
               -  Any immune-suppressive therapy within 4 weeks prior to trial treatment start&#xD;
&#xD;
               -  Known HIV infection&#xD;
&#xD;
          2. Autologous stem cell transplant within 3 months prior to trial treatment start.&#xD;
&#xD;
          3. Concomitant anticancer therapy (e.g. chemotherapy, radiotherapy, hormonal therapy,&#xD;
             immunotherapy, biological response modifier, signal transduction inhibitors).&#xD;
&#xD;
          4. Concomitant treatment with medicinal products that increase the pH (reduce acidity) of&#xD;
             the upper gastrointestinal tract, including, but not limited to, proton-pump&#xD;
             inhibitors (e.g. omeprazole), H2-antagonists (e.g. ranitidine) and antacids. Patients&#xD;
             may be enrolled in the study after a wash-out period sufficient to terminate their&#xD;
             effect.&#xD;
&#xD;
          5. Use of any investigational drug within 21 days prior to trial treatment start.&#xD;
&#xD;
          6. Patients who experienced National Cancer Institute (NCI) Common Terminology Criteria&#xD;
             For Adverse Events (CTCAE) ≥ Grade 3 on PI3K/mTOR inhibitors&#xD;
&#xD;
          7. Any major surgery, chemotherapy or immunotherapy within 21 days prior to trial&#xD;
             treatment start.&#xD;
&#xD;
          8. Symptomatic or progressing Central nervous system (CNS) involvement. Exception:&#xD;
             Patients with meningeal involvement can be included upon discussion between the&#xD;
             sponsor and the investigator.&#xD;
&#xD;
          9. Persisting toxicities NCI CTCAE ≥2 related to prior anticancer therapy&#xD;
&#xD;
         10. Presence of gastrointestinal disease or any other condition that could interfere&#xD;
             significantly with the absorption of the study drug.&#xD;
&#xD;
         11. Severe/unstable angina, myocardial infarction or coronary artery bypass within the&#xD;
             last 3 years prior to trial treatment start, symptomatic congestive heart failure New&#xD;
             York Heart Association (NYHA) Class 3 or 4, hypertension BP&gt;150/100mmHg&#xD;
&#xD;
         12. A serious active infection at the time of treatment, or another serious underlying&#xD;
             medical condition that could impair the ability of the patient to receive treatment.&#xD;
&#xD;
         13. Lack of appropriate contraceptive measures (male and female)&#xD;
&#xD;
         14. Pregnant or lactating women&#xD;
&#xD;
         15. Known HIV infection&#xD;
&#xD;
         16. Significant medical conditions which could jeopardize compliance with the protocol.&#xD;
&#xD;
         17. Uncontrolled diabetes mellitus; patients with controlled diabetes may be enrolled (see&#xD;
             fasting glucose and HbA1c levels in inclusion criteria).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rakesh Popat</last_name>
    <role>Principal Investigator</role>
    <affiliation>Univeristy College London</affiliation>
  </overall_official>
  <overall_official>
    <last_name>David Cunningham</last_name>
    <role>Principal Investigator</role>
    <affiliation>Royal Marsden NHS Foundation Trust</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Paul Fields</last_name>
    <role>Principal Investigator</role>
    <affiliation>Guy's Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Graham Collins</last_name>
    <role>Principal Investigator</role>
    <affiliation>Churchill Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Netanel Horowitz</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Haifa</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Giulino Roth</last_name>
    <role>Principal Investigator</role>
    <affiliation>Weill Cornell Medicine New York</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Carole Soussain</last_name>
    <role>Principal Investigator</role>
    <affiliation>Curie Institute</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Sinisa Radulovic</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institute for Oncology and Radiology Serbia</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ivan Tijanic</last_name>
    <role>Principal Investigator</role>
    <affiliation>Clinical Center Nis</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Nebojsa Andjelkovic</last_name>
    <role>Principal Investigator</role>
    <affiliation>Clinical Center Kragujevac</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Sabrina Kurtovic</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Clinical Center, Sarajevo</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Danijela Mandic</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Clinical Centre of Republic of Srpska</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Weill Cornell Medicine</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Clinical Center Republic of Srpska</name>
      <address>
        <city>Banja Luka</city>
        <zip>78000</zip>
        <country>Bosnia and Herzegovina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Clinical Center Sarajevo</name>
      <address>
        <city>Sarajevo</city>
        <zip>71000</zip>
        <country>Bosnia and Herzegovina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Insitute Curie</name>
      <address>
        <city>Saint-Cloud</city>
        <state>Paris</state>
        <zip>92210</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Univeristy Hospital Haifa</name>
      <address>
        <city>Haifa</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institute for Oncology and radiology of Serbia</name>
      <address>
        <city>Belgrade</city>
        <zip>110000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Center Kragujevac</name>
      <address>
        <city>Kragujevac</city>
        <zip>34000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Center Nis</name>
      <address>
        <city>Nis</city>
        <zip>118000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Guy's Hospital</name>
      <address>
        <city>London</city>
        <zip>SE1 9RT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Marsden NHS Foundation Trust</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University College Hospital London</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Churchill Hospital</name>
      <address>
        <city>Oxford</city>
        <zip>OX3 7DQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Bosnia and Herzegovina</country>
    <country>France</country>
    <country>Israel</country>
    <country>Serbia</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Switzerland</country>
  </removed_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>September 8, 2014</study_first_submitted>
  <study_first_submitted_qc>September 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <disposition_first_submitted>August 22, 2019</disposition_first_submitted>
  <disposition_first_submitted_qc>August 27, 2019</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">September 6, 2019</disposition_first_posted>
  <last_update_submitted>August 27, 2019</last_update_submitted>
  <last_update_submitted_qc>August 27, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 6, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Non Hodgkin Lymphoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT02249429
org study id: PQR309-002
nct id: NCT02249429
lead sponsor: 
collaborator: 
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has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The main goal of this study is to determine the Maximum Tolerated Dose (MTD) and the
      Recommended Phase II Dose (RP2D) as well as preliminary antitumor activity of bimiralisib
      (PQR309) administered orally, as once daily capsules continuously and on intermittent
      schedule in patients with relapsed or refractory lymphomas.
Open-label, non-randomized, multicentre phase 2 study with a safety run-in evaluating
      efficacy and safety of bimiralisib (PQR309) in patients with relapsed or refractory lymphoma.

      The maximum tolerated dose (MTD) of bimiralisib in patients with advanced solid tumors was
      defined as 80 mg once daily given continuously (q.d. schedule) in a previous phase 1 study.
      The safety run-in of this study will follow a modified 3 + 3 design to evaluate the safety of
      60 and 80 mg bimiralisib in patients with relapsed or refractory lymphoma administered p.o.
      once daily during a DLT (dose-limiting toxicity) period of 28 days.

      In the safety run-in, three patients will be treated at 60 mg bimiralisib for 28 days.
      Enrollment and treatment of all three patients may occur simultaneously as 80 mg bimiralisib
      p.o. qd was established as the MTD in solid tumors. Unless a DLT is observed in any of the
      three patients during the first 28 days of treatment, the investigators and the sponsor will
      decide to escalate the dose to 80 mg. Intermittent dosing schedules may be evaluated if,
      based on the overall evaluation of all the clinical and PK (pharmacokinetic) data from this
      and other studies with bimiralisib, data emerge during step 1 of the phase 2 expansion in
      this study, indicating that daily dosing of bimiralisib is not adequately tolerated or
      inefficacious.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Assessment of Change of Tumor Response Criteria in lymphoma patients During Treatment with PQR309 in patients with relapsed or refractory lymphoma according to Cheston Criteria (5)
time frame: 28 day prior to first treatment (baseline), during treatment every 8 weeks during 6 months and every 6 months afterwards up to 1 year)
description: Radiological lymphoma Evaluation (CT or other indicated according to institutional standard practice), clinical examination and bone marrow biopsy
measure: Incidence of serious adverse events (SAE) and severity of all adverse events (AEs)
time frame: Before treatment on Day -1,-2 and during treatment on Day 1,2,8,15,22,36,50, at the end of treatment up to 1 year and 30 days after last dose
description: Continuous dosing and intermittent dosing
measure: Change of pulse rate
time frame: Before treatment on Day -1,-2 and during treatment on Day 1,2,8,15,22,36,50, at the end of treatment up to 1 year and 30 days after last dose
description: Continuous dosing and intermittent dosing
measure: Change in blood pressure
time frame: Before treatment on Day -1,-2 and during treatment on Day 1,2,8,15,22,36,50, subsequently every 4 weeks up to 1 year, at the end of treatment up to 1 year and 30 days after last dose
description: Continuous dosing and intermittent dosing
measure: Change in body temperature
time frame: Before treatment on Day -1,-2 and during treatment on Day 1,2,8,15,22,36,50, subsequently every 4 weeks up to 1 year, at the end of treatment up to 1 year and 30 days after last dose
description: Continuous dosing and intermittent dosing
measure: Change in ECOG (Eastern Cooperative Oncology Group) Performance status
time frame: Before treatment on Day -1,-2 and during treatment on Day 1,2,8,15,22,36,50, subsequently every 4 weeks up to 1 year, at the end of treatment up to 1 year and 30 days after last dose
description: Continuous dosing and intermittent dosing
measure: Change in body weight
time frame: Before treatment on Day -1,-2 and during treatment on Day 1,2,8,15,22,36,50, subsequently every 4 weeks up to 1 year, at the end of treatment up to 1 year and 30 days after last dose
description: Continuous dosing and intermittent dosing
measure: Change in haematology
time frame: Before treatment on Day -1,-2 and during treatment on Day 1,2,8,15,22,36,50, subsequently every 4 weeks up to 1 year, at the end of treatment up to 1 year and 30 days after last dose
description: Continuous dosing and intermittent dosing
measure: Change in blood chemistry
time frame: Before treatment on Day -1 and during treatment on Day 1,22,50, subsequently every 4 weeks up to 1 year, at the end of treatment up to 1 year
description: Continuous dosing and intermittent dosing
measure: Change in ECG (electrocardiogram)
time frame: Before treatment on Day -1 and during treatment on Day 1,22,50, subsequently every 4 weeks up to 1 year, at the end of treatment up to 1 year
description: Continuous dosing and intermittent dosing
measure: Change of urine analysis
time frame: Before treatment on Day -1 and during treatment on Day 1,22,50, subsequently every 4 weeks up to 1 year, at the end of treatment up to 1 year
description: Continuous dosing and intermittent dosing
measure: Change in HbA1c
time frame: Before treatment on Day -1 and during treatment on Day 1,22,50, subsequently every 4 weeks up to 1 year, at the end of treatment up to 1 year
description: Continuous dosing and intermittent dosing
measure: Change in tmax
time frame: During treatment on Day 1,2, 8,15 22, 50
description: Continuous dosing and intermittent dosing
measure: Change in Cmax
time frame: During treatment on Day 1,2, 8,15 22, 50
description: Continuous dosing and intermittent dosing
measure: Change in AUC 0-24
time frame: During treatment on Day 1,2, 8,15 22, 50
description: Continuous dosing and intermittent dosing
measure: Change in AUClast
time frame: During treatment on Day 1,2, 8,15 22, 50
description: Continuous dosing and intermittent dosing
measure: Change in AUC0-∞,
time frame: During treatment on Day 1,2, 8,15 22, 50
description: Continuous dosing and intermittent dosing
measure: Change in t1/2
time frame: During treatment on Day 1,2, 8,15 22, 50
description: Continuous dosing and intermittent dosing
measure: Change in RAC
time frame: During treatment on Day 1,2, 8,15 22, 50
description: Continuous dosing and intermittent dosing
measure: Change in insulin/ C-Peptide/ glucose
time frame: During treatment on Day 1,2, 8,15 22, 50
description: Continuous dosing and intermittent dosing
arm group label: bimiralisib (PQR309)
arm group type: Experimental
intervention type: Drug
intervention name: bimiralisib
description: 60 mg or 80 mg bimiralisib per oral (p.o.) once daily or intermittent dosing (120mg,140mg and 160mg) until unacceptable AE, disease progression, patient's request for withdrawal, investigator judgement or death - whichever comes first.
arm group label: bimiralisib (PQR309)
other name: PQR309
other name: PI3K Inhibitor (phosphatidylinositol 3-kinase)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Rakesh Popat
role: Principal Investigator
affiliation: Univeristy College London
last name: David Cunningham
role: Principal Investigator
affiliation: Royal Marsden NHS Foundation Trust
last name: Paul Fields
role: Principal Investigator
affiliation: Guy's Hospital
last name: Graham Collins
role: Principal Investigator
affiliation: Churchill Hospital
last name: Netanel Horowitz
role: Principal Investigator
affiliation: University of Haifa
last name: Giulino Roth
role: Principal Investigator
affiliation: Weill Cornell Medicine New York
last name: Carole Soussain
role: Principal Investigator
affiliation: Curie Institute
last name: Sinisa Radulovic
role: Principal Investigator
affiliation: Institute for Oncology and Radiology Serbia
last name: Ivan Tijanic
role: Principal Investigator
affiliation: Clinical Center Nis
last name: Nebojsa Andjelkovic
role: Principal Investigator
affiliation: Clinical Center Kragujevac
last name: Sabrina Kurtovic
role: Principal Investigator
affiliation: University Clinical Center, Sarajevo
last name: Danijela Mandic
role: Principal Investigator
affiliation: University Clinical Centre of Republic of Srpska
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country: Bosnia and Herzegovina
country: France
country: Israel
country: Serbia
country: United Kingdom
country: United States
country: Switzerland
responsible party type: Sponsor
mesh term: Lymphoma
sharing ipd: No