<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/NCT02966730</url>
  </required_header>
  <id_info>
    <org_study_id>16-396</org_study_id>
    <nct_id>NCT02966730</nct_id>
  </id_info>
  <brief_title>Ibrutinib for Patients With Follicular Lymphoma Without Complete Response to Initial Chemoimmunotherapy</brief_title>
  <official_title>Protocol 20060 (PCYC): A Multicenter, Open-Label Pilot Study of Follicular Lymphoma Ibrutinib Consolidation for FDG-PET Positivity After Frontline Chemoimmunotherapy (FLIPP)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Memorial Sloan Kettering Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Fox Chase Cancer Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Pharmacyclics LLC.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Memorial Sloan Kettering Cancer Center</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to find out how successful ibrutinib is at putting follicular&#xD;
      lymphoma into full remission. In this study, remission will be determined by achieving a&#xD;
      normal PET scan after treatment. A PET scan is an imaging test that looks for active&#xD;
      lymphoma. People who don't have a complete remission on PET after their first treatment are&#xD;
      at high risk for having their lymphoma return. This study will investigate if ibrutinib will&#xD;
      help participants achieve a complete remission without giving additional chemotherapy. The&#xD;
      study will also investigate any possible side effects of the study drug ibrutinib.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Lack of accrual&#xD;
  </why_stopped>
  <start_date type="Actual">November 2016</start_date>
  <completion_date type="Actual">June 20, 2019</completion_date>
  <primary_completion_date type="Actual">June 20, 2019</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <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>Rate of conversion from FDG-PET positive to negative</measure>
    <time_frame>12 months</time_frame>
    <description>The primary objective is to determine the rate of conversion from FDG-PET positive to negative at 12 months from the start of ibrutinib in patients receiving at least 6 months of Ibrutinib consolidation therapy for follicular lymphoma achieving at least a PR but remaining FDG-PET positive after first line chemoimmunotherapy.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">2</enrollment>
  <condition>Follicular Lymphoma</condition>
  <condition>Follicular Lymphoma, Grade 1</condition>
  <condition>Follicular Lymphoma, Grade 2</condition>
  <condition>Follicular Lymphoma Grade IIIa</condition>
  <arm_group>
    <arm_group_label>Follicular Lymphoma</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be receive Ibrutinib as an oral capsule preparation once daily for a period of 2 years. The dose will be 560mg daily. Toxicities will be recorded and graded. Response to treatment will be determined by FDG-PET imaging every 6 months, or as clinically indicated, in conjunction with clinical assessment by a physician, including physical examination, every 4 weeks from day 1 (baseline) for the first 3 months and then every 3 months until the end of treatment at 2 years.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ibrutinib</intervention_name>
    <description>Ibrutinib will be administered orally, on a once daily continuous dosing schedule and in an outpatient setting. Treatment will continue for 2 years and there will be no planned treatment breaks. The dose of Ibrutinib will be initiated at 560mg per day, which will remain constant throughout the study period, unless otherwise specified.</description>
    <arm_group_label>Follicular Lymphoma</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Follicular lymphoma with histology documented by the participating institution (grades&#xD;
             1, 2 or 3a).&#xD;
&#xD;
             °For subjects with presumptive evidence of transformation based on clinical assessment&#xD;
             of factors such as, but not limited to, increasing lactate dehydrogenase (LDH),&#xD;
             rapidly worsening disease, or frequent B-symptoms, a pre-treatment biopsy is required&#xD;
             to rule out large cell transformation&#xD;
&#xD;
          -  Completion of a full course of first line immunochemotherapy including rituximab OR&#xD;
             completion of 4 cycles of first line immunochemotherapy including rituximab if&#xD;
             intolerant (e.g. which include, but are not limited to, R-CHOP, R-CVP,&#xD;
             Bendamustine-R).&#xD;
&#xD;
          -  Patients must have achieved PR to primary treatment and not be refractory to prior&#xD;
             treatment.&#xD;
&#xD;
          -  Residual FDG-PET activity defined as Deauville 4 or 5 on a PET-CT within 3 and 8 weeks&#xD;
             post the last dose of front line therapy.&#xD;
&#xD;
          -  Treatment must begin within 90 days of the last dose of immunochemotherapy.&#xD;
&#xD;
          -  Men and women ≥ 18 years of age.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.&#xD;
&#xD;
          -  ≥ 1 measurable disease site on computed tomography (CT) scan or positron emission&#xD;
             tomography (PET) (1.5 cm in longest dimension). (In select cases, for example&#xD;
             extremity lesions, an MRI may be substituted.)&#xD;
&#xD;
          -  Life expectancy of &gt; 3 months, in the opinion of the investigator.&#xD;
&#xD;
          -  Female subjects who are of non-reproductive potential (i.e. post-menopausal by history&#xD;
             - no menses for ≥ 2 years; OR history of hysterectomy; OR history of bilateral tubal&#xD;
             ligation; OR history of bilateral oophorectomy). Female subjects of childbearing&#xD;
             potential must have a negative serum pregnancy test upon study entry.&#xD;
&#xD;
          -  Male and female subjects who agree to use highly effective methods of birth control&#xD;
             (e.g., implants, injectables, combined oral contraceptives, some intrauterine devices&#xD;
             [IUDs], sexual abstinence, or sterilized partner) and a barrier method (e.g. condoms,&#xD;
             vaginal ring, sponge, etc) during the period of therapy and for 30 days (females) and&#xD;
             90 days (males) after the last dose of study drug.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Medically apparent central nervous system lymphoma or leptomeningeal disease.&#xD;
&#xD;
          -  History of any other active malignancies.&#xD;
&#xD;
          -  History of any prior cancer curatively treated within the last two years except:&#xD;
&#xD;
               -  Any non-melanoma skin cancer&#xD;
&#xD;
               -  Any cancer excised, not treated with chemotherapy and with less than a 30% chance&#xD;
                  of recurrence within the next 2 years from registration&#xD;
&#xD;
          -  History of any organ transplantation.&#xD;
&#xD;
          -  History of stroke or intracranial hemorrhage within 6 months prior to enrollment.&#xD;
&#xD;
          -  More than one prior line of any systemic chemoimmunotherapy for follicular lymphoma.&#xD;
&#xD;
          -  Chemotherapy ≤ 21 days prior to first administration of study treatment and/or&#xD;
             monoclonal antibody ≥ 3 weeks prior to first administration of study treatment.&#xD;
&#xD;
          -  Prior exposure to radio- or toxin-immunoconjugates.&#xD;
&#xD;
          -  Concurrent use of warfarin or other vitamin K antagonists.&#xD;
&#xD;
          -  Concurrent use of a strong cytochrome P450 (CYP)3A4/5 inhibitor.&#xD;
&#xD;
          -  Concurrent systemic immunosuppressant therapy (e.g., cyclosporine A, tacrolimus, etc.,&#xD;
             or chronic administration of &gt; 20 mg/day of prednisone) within 28 days of the first&#xD;
             dose of study drug.&#xD;
&#xD;
          -  Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.&#xD;
&#xD;
          -  Significant screening electrocardiogram (ECG) abnormalities including left bundle&#xD;
             branch block, 2nd degree atrioventricular (AV) block type II, 3rd degree block, or&#xD;
             corrected QT interval (QTc) &gt;/= 470 msec.&#xD;
&#xD;
          -  Clinically significant cardiovascular disease such as uncontrolled or symptomatic&#xD;
             arrhythmias, congestive heart failure (new York Heart Association &gt;Class 2), unstable&#xD;
             angina, uncontrolled hypertension, or myocardial infarction within 6 months of&#xD;
             Screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart&#xD;
             Association Functional Classification.&#xD;
&#xD;
          -  Any uncontrolled active systemic infection or recent infection requiring intravenous&#xD;
             anti-infective treatment that was complete ≤ 14 days before the first dose of study&#xD;
             drug.&#xD;
&#xD;
          -  Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved&#xD;
             to Common Terminology Criteria for Adverse Event (CTCAE, version 4.0), Grade 0 or 1,&#xD;
             or to the levels dictated in the inclusion/exclusion criteria with the exception of&#xD;
             alopecia.&#xD;
&#xD;
          -  Known bleeding diathesis (e.g., von Willebrand's disease) or hemophilia.&#xD;
&#xD;
          -  Known history of infection with human immunodeficiency virus (HIV) or history of&#xD;
             active or chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV),&#xD;
             or any uncontrolled active systemic infection. Hepatitis B surface antigen must be&#xD;
             confirmed negative within on year before enrollment. Subjects who are positive for&#xD;
             hepatitis B core antibody or hepatitis B surface antigen must have a negative&#xD;
             polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive&#xD;
             will be excluded.&#xD;
&#xD;
          -  Any of the following abnormalities&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) &lt;750 cells/mm^3 (0.75 x 10^9/L)&#xD;
&#xD;
               -  Platelet count &lt;50,000 cells/mm^3 (50 x 10^9/L) independent of transfusion&#xD;
                  support&#xD;
&#xD;
               -  Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≥3.0 x upper&#xD;
                  limit of normal (ULN)&#xD;
&#xD;
               -  Creatinine clearance (CrCl) &lt;30mL/min&#xD;
&#xD;
               -  Hemoglobin &lt;8.0 g/dL&#xD;
&#xD;
               -  Bilirubin &gt;1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of&#xD;
                  non-hepatic origin)&#xD;
&#xD;
               -  PT/INR &gt;1.5 x ULN and PTT (aPTT) &gt;1.5 x ULN(unless abnormalities are unrelated to&#xD;
                  coagulopathy or bleeding disorder).&#xD;
&#xD;
          -  Unable to swallow capsules or disease significantly affecting gastrointestinal&#xD;
             function such as malabsorption syndrome, resection of the stomach or small bowel, or&#xD;
             complete bowel obstruction.&#xD;
&#xD;
          -  Major surgery planned within 4 weeks of the first dose of study drug.&#xD;
&#xD;
          -  Any life-threatening illness, medical condition, including uncontrolled diabetes&#xD;
             mellitus (DM), or organ system dysfunction that, in the opinion of the investigator,&#xD;
             could compromise the subject's safety or put the study outcomes at undue risk.&#xD;
&#xD;
          -  Concurrent enrollment in another therapeutic investigational study or have previously&#xD;
             taken ibrutinib.&#xD;
&#xD;
          -  Lactating or pregnant.&#xD;
&#xD;
          -  Unwilling or unable to participate in all required study evaluations and procedures.&#xD;
&#xD;
          -  Unable to understand the purpose and risks of the study and to provide a signed and&#xD;
             dated informed consent form (ICF) and authorization to use protected health&#xD;
             information (in accordance with national and local subject privacy regulations).&#xD;
&#xD;
          -  Currently active, clinically significant hepatic impairment Child-Pugh class B or C&#xD;
             according to the Child Pugh classification.&#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>Ariela Noy, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Memorial Sloan Kettering Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Basking Ridge</name>
      <address>
        <city>Basking Ridge</city>
        <state>New Jersey</state>
        <zip>07920</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Monmouth</name>
      <address>
        <city>Middletown</city>
        <state>New Jersey</state>
        <zip>07748</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Bergen</name>
      <address>
        <city>Montvale</city>
        <state>New Jersey</state>
        <zip>07645</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center @ Commack</name>
      <address>
        <city>Commack</city>
        <state>New York</state>
        <zip>11725</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Westchester</name>
      <address>
        <city>Harrison</city>
        <state>New York</state>
        <zip>10604</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan - Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering at Mercy Medical Center</name>
      <address>
        <city>Rockville Centre</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fox Chase Cancer Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.mskcc.org/</url>
    <description>Memorial Sloan Kettering Cancer Center</description>
  </link>
  <verification_date>June 2019</verification_date>
  <study_first_submitted>November 14, 2016</study_first_submitted>
  <study_first_submitted_qc>November 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 17, 2016</study_first_posted>
  <last_update_submitted>June 21, 2019</last_update_submitted>
  <last_update_submitted_qc>June 21, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">June 25, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>follicular lymphoma</keyword>
  <keyword>Ibrutinib</keyword>
  <keyword>FLIPP</keyword>
  <keyword>16-396</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, Follicular</mesh_term>
  </condition_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/NCT02966730
org study id: 16-396
nct id: NCT02966730
lead sponsor: 
collaborator: 
collaborator: 
is fda regulated drug: Yes
The purpose of this study is to find out how successful ibrutinib is at putting follicular
      lymphoma into full remission. In this study, remission will be determined by achieving a
      normal PET scan after treatment. A PET scan is an imaging test that looks for active
      lymphoma. People who don't have a complete remission on PET after their first treatment are
      at high risk for having their lymphoma return. This study will investigate if ibrutinib will
      help participants achieve a complete remission without giving additional chemotherapy. The
      study will also investigate any possible side effects of the study drug ibrutinib.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Rate of conversion from FDG-PET positive to negative
time frame: 12 months
description: The primary objective is to determine the rate of conversion from FDG-PET positive to negative at 12 months from the start of ibrutinib in patients receiving at least 6 months of Ibrutinib consolidation therapy for follicular lymphoma achieving at least a PR but remaining FDG-PET positive after first line chemoimmunotherapy.
arm group label: Follicular Lymphoma
arm group type: Experimental
description: Participants will be receive Ibrutinib as an oral capsule preparation once daily for a period of 2 years. The dose will be 560mg daily. Toxicities will be recorded and graded. Response to treatment will be determined by FDG-PET imaging every 6 months, or as clinically indicated, in conjunction with clinical assessment by a physician, including physical examination, every 4 weeks from day 1 (baseline) for the first 3 months and then every 3 months until the end of treatment at 2 years.
intervention type: Drug
intervention name: Ibrutinib
description: Ibrutinib will be administered orally, on a once daily continuous dosing schedule and in an outpatient setting. Treatment will continue for 2 years and there will be no planned treatment breaks. The dose of Ibrutinib will be initiated at 560mg per day, which will remain constant throughout the study period, unless otherwise specified.
arm group label: Follicular Lymphoma
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ariela Noy, MD
role: Principal Investigator
affiliation: Memorial Sloan Kettering Cancer Center
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: https://www.mskcc.org/
description: Memorial Sloan Kettering Cancer Center
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, Follicular