<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/NCT02240719</url>
  </required_header>
  <id_info>
    <org_study_id>637004</org_study_id>
    <secondary_id>637004</secondary_id>
    <secondary_id>CRAD001NUS235T</secondary_id>
    <secondary_id>UCDCC#245</secondary_id>
    <secondary_id>NCI-2014-01934</secondary_id>
    <nct_id>NCT02240719</nct_id>
  </id_info>
  <brief_title>Everolimus and Bendamustine Hydrochloride in Treating Patients With Relapsed or Refractory Hematologic Cancer</brief_title>
  <official_title>Phase I Study of Everolimus + Bendamustine in Patients With Relapsed/Refractory Hematological Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, Davis</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novartis</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, Davis</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase I trial studies the side effects and the best dose of everolimus when given&#xD;
      together with bendamustine hydrochloride in treating patients with cancer of the blood&#xD;
      (hematologic cancer) that has returned after a period of improvement (relapsed) or did not&#xD;
      get better with a particular treatment (refractory). Everolimus may prevent cancer cells from&#xD;
      growing by blocking a protein that is needed for cell growth. Drugs used in chemotherapy,&#xD;
      such as bendamustine hydrochloride, work in different ways to stop the growth of cancer&#xD;
      cells, either by killing the cells, by stopping them from dividing, or by stopping them from&#xD;
      spreading. Giving everolimus together with bendamustine hydrochloride may be a better&#xD;
      treatment for hematologic cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the maximum tolerated dose (MTD) of everolimus when administered in&#xD;
      combination with bendamustine (bendamustine hydrochloride) in defined hematologic&#xD;
      malignancies.&#xD;
&#xD;
      II. To determine the safety and tolerability of administering everolimus in combination with&#xD;
      bendamustine chemotherapy.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the efficacy of everolimus when administered in combination with bendamustine&#xD;
      in adult patients with relapsed/refractory hematological malignancies.&#xD;
&#xD;
      OUTLINE: This is a dose-escalation study of everolimus.&#xD;
&#xD;
      Patients receive bendamustine hydrochloride intravenously (IV) over 30 minutes on days 1 and&#xD;
      2 and everolimus orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in&#xD;
      the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up for 30 days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">April 9, 2018</completion_date>
  <primary_completion_date type="Actual">April 9, 2018</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>MTD of everolimus, defined as the dose that produces dose-limiting toxicity (DLT) in =&lt; 1/6 patients, determined by incidence of DLT graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0</measure>
    <time_frame>28 days</time_frame>
    <description>The toxicities observed at each dose level will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by NCI CTCAE version 4.0) and nadir or maximum values for the laboratory measures, time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and by course.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence and severity of adverse events as defined by the NCI CTCAE version 4.03</measure>
    <time_frame>Up to 30 days post-treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response rates (complete response, partial response, stable disease)</measure>
    <time_frame>Up to 30 days post-treatment</time_frame>
    <description>Response rate among patients with measurable disease will be summarized by exact binomial confidence intervals.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Recurrent Adult Diffuse Large Cell Lymphoma</condition>
  <condition>Recurrent Adult Hodgkin Lymphoma</condition>
  <condition>Recurrent Grade 1 Follicular Lymphoma</condition>
  <condition>Recurrent Grade 2 Follicular Lymphoma</condition>
  <condition>Recurrent Grade 3 Follicular Lymphoma</condition>
  <condition>Recurrent Mantle Cell Lymphoma</condition>
  <condition>Refractory Chronic Lymphocytic Leukemia</condition>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Everolimus + Bendamustine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive bendamustine hydrochloride IV over 30 minutes on days 1 and 2 and everolimus PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>everolimus</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Everolimus + Bendamustine</arm_group_label>
    <other_name>42-O-(2-hydroxy)ethyl rapamycin</other_name>
    <other_name>Afinitor</other_name>
    <other_name>RAD001</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>bendamustine hydrochloride</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Everolimus + Bendamustine</arm_group_label>
    <other_name>bendamustin hydrochloride</other_name>
    <other_name>bendamustine</other_name>
    <other_name>cytostasan hydrochloride</other_name>
    <other_name>Treanda</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Measurable disease&#xD;
&#xD;
          -  Baseline hemoglobin level of &gt; 7.0 g/dl&#xD;
&#xD;
          -  Understand and voluntarily sign an informed consent form&#xD;
&#xD;
          -  Able to adhere to the study visit schedule and other protocol requirements&#xD;
&#xD;
          -  All the patients need to have biopsy proven active disease at the time of clinical&#xD;
             trial&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group performance status of =&lt; 2 study entry&#xD;
&#xD;
          -  Absolute neutrophil count &gt;= 1,000/mm^3&#xD;
&#xD;
          -  Platelet count &gt;= 50,000/mm^3&#xD;
&#xD;
          -  Calculated creatinine clearance &gt; 40 ml/min or 24 hour urine&#xD;
&#xD;
          -  Total bilirubin =&lt; 2 x upper limit of normal&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and&#xD;
             alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =&lt; 3 x&#xD;
             upper limit of normal&#xD;
&#xD;
          -  International normalized ratio &lt; 2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any serious medical condition, laboratory abnormality, or psychiatric illness that&#xD;
             would prevent the subject from signing the informed consent form&#xD;
&#xD;
          -  Currently part of or have participated in any clinical investigation with an&#xD;
             investigational drug within 1 month prior to dosing&#xD;
&#xD;
          -  Any severe and/or uncontrolled medical conditions&#xD;
&#xD;
          -  Uncontrolled diabetes mellitus&#xD;
&#xD;
          -  Known impairment of gastrointestinal (GI) function or GI disease that may&#xD;
             significantly alter the absorption of oral everolimus&#xD;
&#xD;
          -  Currently receiving anticancer therapies or who have received anticancer therapies&#xD;
             within 2 weeks of the start of everolimus&#xD;
&#xD;
          -  Known hypersensitivity to everolimus or bendamustine&#xD;
&#xD;
          -  Known central nervous system (CNS) disease (NHL, diffuse large B cell lymphoma&#xD;
             [DLBCL])&#xD;
&#xD;
          -  Recent major surgery within 14 days prior to cycle 1, day 1&#xD;
&#xD;
          -  Taking strong cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors&#xD;
&#xD;
          -  Received live attenuated vaccines&#xD;
&#xD;
          -  Known sero-positive for active or past viral infection with human immunodeficiency&#xD;
             virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); patients who are&#xD;
             sero-positive because of hepatitis B virus vaccine are eligible&#xD;
&#xD;
          -  History of another primary malignancy&#xD;
&#xD;
          -  History of non-compliance to medical regimens or who are considered potentially&#xD;
             unreliable or will not be able to complete the entire study&#xD;
&#xD;
          -  Pregnant or nursing (lactating) women&#xD;
&#xD;
          -  Women of childbearing potential&#xD;
&#xD;
          -  Women are considered post-menopausal and not of child-bearing potential if they have&#xD;
             had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile&#xD;
             (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral&#xD;
             oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior&#xD;
             to randomization; in the case of oophorectomy alone, only when the reproductive status&#xD;
             of the woman has been confirmed by follow up hormone level assessment is she&#xD;
             considered not of child-bearing potential&#xD;
&#xD;
          -  Male patients whose sexual partner(s) are WOCBP who are not willing to use adequate&#xD;
             contraception, during the study and for 8 weeks after the end of treatment&#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>Mehrdad Abedi</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, Davis</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California Davis</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>September 12, 2014</study_first_submitted>
  <study_first_submitted_qc>September 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 16, 2014</study_first_posted>
  <last_update_submitted>January 2, 2019</last_update_submitted>
  <last_update_submitted_qc>January 2, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 4, 2019</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>Multiple Myeloma</mesh_term>
    <mesh_term>Lymphoma, Follicular</mesh_term>
    <mesh_term>Leukemia, Lymphocytic, Chronic, B-Cell</mesh_term>
    <mesh_term>Hodgkin Disease</mesh_term>
    <mesh_term>Lymphoma, Mantle-Cell</mesh_term>
    <mesh_term>Lymphoma, Large B-Cell, Diffuse</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Everolimus</mesh_term>
    <mesh_term>Bendamustine Hydrochloride</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/NCT02240719
org study id: 637004
secondary id: 637004
secondary id: CRAD001NUS235T
secondary id: UCDCC#245
secondary id: NCI-2014-01934
nct id: NCT02240719
lead sponsor: 
collaborator: 
has dmc: Yes
This phase I trial studies the side effects and the best dose of everolimus when given
      together with bendamustine hydrochloride in treating patients with cancer of the blood
      (hematologic cancer) that has returned after a period of improvement (relapsed) or did not
      get better with a particular treatment (refractory). Everolimus may prevent cancer cells from
      growing by blocking a protein that is needed for cell growth. Drugs used in chemotherapy,
      such as bendamustine hydrochloride, 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. Giving everolimus together with bendamustine hydrochloride may be a better
      treatment for hematologic cancer.
PRIMARY OBJECTIVES:

      I. To determine the maximum tolerated dose (MTD) of everolimus when administered in
      combination with bendamustine (bendamustine hydrochloride) in defined hematologic
      malignancies.

      II. To determine the safety and tolerability of administering everolimus in combination with
      bendamustine chemotherapy.

      SECONDARY OBJECTIVES:

      I. To determine the efficacy of everolimus when administered in combination with bendamustine
      in adult patients with relapsed/refractory hematological malignancies.

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

      Patients receive bendamustine hydrochloride intravenously (IV) over 30 minutes on days 1 and
      2 and everolimus orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in
      the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up for 30 days.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: MTD of everolimus, defined as the dose that produces dose-limiting toxicity (DLT) in =< 1/6 patients, determined by incidence of DLT graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
time frame: 28 days
description: The toxicities observed at each dose level will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by NCI CTCAE version 4.0) and nadir or maximum values for the laboratory measures, time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and by course.
measure: Incidence and severity of adverse events as defined by the NCI CTCAE version 4.03
time frame: Up to 30 days post-treatment
measure: Response rates (complete response, partial response, stable disease)
time frame: Up to 30 days post-treatment
description: Response rate among patients with measurable disease will be summarized by exact binomial confidence intervals.
arm group label: Everolimus + Bendamustine
arm group type: Experimental
description: Patients receive bendamustine hydrochloride IV over 30 minutes on days 1 and 2 and everolimus PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: everolimus
description: Given PO
arm group label: Everolimus + Bendamustine
other name: 42-O-(2-hydroxy)ethyl rapamycin
other name: Afinitor
other name: RAD001
intervention type: Drug
intervention name: bendamustine hydrochloride
description: Given IV
arm group label: Everolimus + Bendamustine
other name: bendamustin hydrochloride
other name: bendamustine
other name: cytostasan hydrochloride
other name: Treanda
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Mehrdad Abedi
role: Principal Investigator
affiliation: University of California, Davis
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Multiple Myeloma
mesh term: Lymphoma, Follicular
mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
mesh term: Hodgkin Disease
mesh term: Lymphoma, Mantle-Cell
mesh term: Lymphoma, Large B-Cell, Diffuse
mesh term: Recurrence
mesh term: Everolimus
mesh term: Bendamustine Hydrochloride