<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/NCT01691807</url>
  </required_header>
  <id_info>
    <org_study_id>113603</org_study_id>
    <nct_id>NCT01691807</nct_id>
  </id_info>
  <brief_title>Drug-drug Interaction Study of Ofatumumab With Bendamustine in Subjects With Indolent B-cell Non-Hodgkin's Lymphoma</brief_title>
  <official_title>An Open-label Phase I Drug-drug Interaction Study of Ofatumumab With Bendamustine for the Treatment of Subjects With Indolent B-cell Non-Hodgkin's Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the potential drug-drug interactions between&#xD;
      ofatumumab and bendamustine in subjects with previously untreated or relapsed indolent B-cell&#xD;
      non-Hodgkin's lymphoma (NHL).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this study is to evaluate the potential drug-drug interactions between&#xD;
      ofatumumab and bendamustine in subjects with previously untreated or relapsed indolent B-cell&#xD;
      non-Hodgkin's lymphoma (NHL). Ofatumumab and bendamustine will be administered alone and in&#xD;
      combination in a two-arm, open-label study to evaluate the pharmacokinetic profile, safety,&#xD;
      tolerability, and efficacy of ofatumumab and bendamustine.&#xD;
&#xD;
      The primary objective of the study is to evaluate pharmacokinetic parameters of ofatumumab&#xD;
      and bendamustine alone and in combination. Secondary objectives are to evaluate safety,&#xD;
      tolerability, and efficacy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2013</start_date>
  <completion_date type="Actual">December 2015</completion_date>
  <primary_completion_date type="Actual">December 2015</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetic measures of Cmax and Area Under the Curve by analysis of blood samples for the amount of each drug present at different timepoints.</measure>
    <time_frame>4 months</time_frame>
    <description>The amount of ofatumumab and bendamustine in the blood will be measured when given individually or together to obtain Cmax and Area Under the Curve. Bendamustine levels will be collected at Cycles 1 and 2: Predose, 0.25, 0.5, 0.75, 1 (end of infusion), 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, and 24 hours. Ofatumumab will be collected at Cycle 4: Predose, end of infusion, then 1, 2, 24, and 72 hours after end of infusion, then once each on Days 8, 15, and 22.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in vital signs and the number adverse events</measure>
    <time_frame>14 months</time_frame>
    <description>Changes in vital signs will be measured during the entire study to determine any effect on the subjects health. Also the recording of all adverse events that occur during the study will be collected for analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measure the extent of the disease by CT scan or flow cytometry analysis</measure>
    <time_frame>14 months</time_frame>
    <description>Dimension measurement assessments by CT scan of disease will be collected at Screen, Cycle 5, 3 month follow up visit, and 6 month follow up visit. Flow cytometry measurements will be collected at Screen and Weeks 1, 2, 5, 13, 21, 41, and 53.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Cancer</condition>
  <arm_group>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>bendamustine and ofatumumab treatment of NHL</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ofatumumab only treatment of NHL</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ofatumumab</intervention_name>
    <description>treatment for NHL</description>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_label>Arm B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>bendamustine</intervention_name>
    <description>treatment for NHL</description>
    <arm_group_label>Arm A</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects with previously untreated or relapsed indolent B-cell NHL requiring&#xD;
             treatment. Indolent NHL is defined as small lymphocytic lymphoma (SLL),&#xD;
             lymphoplasmacytic lymphoma (LPL), marginal zone lymphoma (MZL), and follicular&#xD;
             lymphoma (FL); grades 1, 2, and 3A, defined according to WHO guidelines. Tumor&#xD;
             verified to be CD20+ positive from a previous or current lymph node biopsy.&#xD;
&#xD;
          -  At least 4 weeks after previous anti-cancer chemotherapy, or radiotherapy treatment.&#xD;
&#xD;
          -  At least 12 weeks after previous anti-CD20 radioimmunotherapy, anti-CD20 antibody&#xD;
             treatment, and non-anti-CD20 monoclonal antibody treatment.&#xD;
&#xD;
          -  Subjects who give consent to this study participation and sign the informed consent&#xD;
             form.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.&#xD;
&#xD;
          -  Age greater than or equal to 18 years at informed consent.&#xD;
&#xD;
          -  A female subject is eligible to participate if she is of Non-childbearing potential or&#xD;
             required to use a contraception method.&#xD;
&#xD;
          -  Male subjects with female partners of child-bearing potential must agree to use a&#xD;
             contraception method.&#xD;
&#xD;
          -  Subjects must agree to use contraception until 12 months after the last dose of study&#xD;
             drug.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects who failed to achieve a complete remission (CR) or partial remission (PR) or&#xD;
             progressed within 6 months of last rituximab-containing therapy&#xD;
&#xD;
          -  Previous treatment with ofatumumab.&#xD;
&#xD;
          -  Prior bendamustine treatment not resulting in a complete remission and partial&#xD;
             remission for at least 6 months.&#xD;
&#xD;
          -  Previous allogeneic stem cell transplant.&#xD;
&#xD;
          -  Previous autologous stem cell transplant.&#xD;
&#xD;
          -  High dose steroids greater than or equal to 100 mg prednisone/day (or equivalent) for&#xD;
             greater than or equal to 7 consecutive days, given as concomitant medication, within 3&#xD;
             months prior to randomization. No more than 20 mg prednisone or equivalent daily at&#xD;
             the time of randomization.&#xD;
&#xD;
          -  Grade 3b follicular lymphoma or evidence that the indolent lymphoma has transformed to&#xD;
             aggressive lymphoma as verified by biopsy confirmation.&#xD;
&#xD;
          -  Known central nervous system involvement by NHL.&#xD;
&#xD;
          -  Other past or current malignancy. Subjects who have been free of malignancy for at&#xD;
             least 2 years, or have a history of definitively treated non-melanoma skin cancer, or&#xD;
             successfully treated in situ carcinoma, are eligible.&#xD;
&#xD;
          -  Chronic or current active infectious disease requiring systemic antibiotics,&#xD;
             antifungal, or antiviral treatment such as, but not limited to, chronic renal&#xD;
             infection, chronic chest infection with bronchiectasis, tuberculosis, and active&#xD;
             Hepatitis B or C. Prophylactic antibiotics to prevent recurrent of a prior infection&#xD;
             (such as shingles, sinusitis or upper respiratory infection) is allowed.&#xD;
&#xD;
          -  Clinically significant cardiac disease as judged by the investigator, including&#xD;
             unstable angina, acute myocardial infarction within 6 months of randomization, and&#xD;
             uncontrolled congestive heart failure (CHF) or arrhythmia. Patients with a history of&#xD;
             CHF or arrhythmia are eligible if their cardiac disease is well controlled on a stable&#xD;
             medical regimen.&#xD;
&#xD;
          -  History of significant cerebrovascular disease or event with significant symptoms or&#xD;
             sequelae (as judged by the investigator).&#xD;
&#xD;
          -  Significant concurrent, uncontrolled medical condition that in the opinion of the&#xD;
             investigator contraindicates participation this study.&#xD;
&#xD;
          -  Positive serology for Hepatitis B (HB) defined as a positive test for Hepatitis B&#xD;
             surface antigen (HBsAg). In addition, if negative for HBsAg but Hepatitis B core&#xD;
             antibody (HBcAb) positive (regardless of Hepatitis B surface antibody [HBsAb] status),&#xD;
             a HB DNA test will be performed and if positive the subject will be excluded. If HBV&#xD;
             DNA is negative, the subject may be included but must undergo Hepatitis B virus (HBV)&#xD;
             DNA monitoring (see Section 7.7.5). Prophylactic antiviral therapy may be initiated at&#xD;
             the discretion of the investigator.&#xD;
&#xD;
          -  Current active liver or biliary disease (subjects with Gilbert's syndrome or&#xD;
             asymptomatic gallstones, liver metastases related to indolent NHL or otherwise stable&#xD;
             chronic liver disease per investigator assessment, are eligible).&#xD;
&#xD;
          -  Known human immunodeficiency virus (HIV) positive.&#xD;
&#xD;
          -  Screening laboratory values:&#xD;
&#xD;
               -  platelets &lt; 100 x 109/L (unless due to lymphoma involvement of the bone marrow)&#xD;
&#xD;
               -  neutrophils &lt; 1.5 x 109/L (unless due to lymphoma involvement of the bone marrow)&#xD;
&#xD;
               -  serum creatinine &gt; 1.5 times the institution's upper limit of normal (ULN);&#xD;
                  subjects with a serum creatinine &gt; 1.5 ULN will be eligible if the calculated&#xD;
                  creatinine clearance [Cockcroft, 1976] or creatinine clearance from a 24-hour&#xD;
                  urine collection is ≥ 40 mL/min&#xD;
&#xD;
               -  total bilirubin &gt; 1.5 times ULN (unless due to liver involvement by lymphoma or&#xD;
                  Gilbert's syndrome)&#xD;
&#xD;
               -  transaminases &gt; 2 times ULN&#xD;
&#xD;
          -  Known or suspected hypersensitivity to ofatumumab, bendamustine, or mannitol.&#xD;
&#xD;
          -  Treatment with any known non-marketed drug substance or experimental therapy within 5&#xD;
             terminal half-lives or 4 weeks prior to Visit 1, whichever is longer or currently&#xD;
             participating in any other interventional clinical study&#xD;
&#xD;
          -  Lactating women, women with a positive pregnancy test at Visit 1, or women (of&#xD;
             childbearing potential) as well as men with partners of childbearing potential, who&#xD;
             are not willing to use adequate contraception until 12 months after the last dose of&#xD;
             study drug. Adequate contraception is defined in Section 8.1.&#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>Novartis Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294-3300</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Southaven</city>
        <state>Mississippi</state>
        <zip>38671</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Morgantown</city>
        <state>West Virginia</state>
        <zip>26506</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2018</verification_date>
  <study_first_submitted>September 13, 2012</study_first_submitted>
  <study_first_submitted_qc>September 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2012</study_first_posted>
  <last_update_submitted>February 27, 2018</last_update_submitted>
  <last_update_submitted_qc>February 27, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">February 28, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Non-Hodgkin's Lymphoma</keyword>
  <keyword>drug-drug interaction</keyword>
  <keyword>ofatumumab</keyword>
  <keyword>bendamustine</keyword>
  <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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bendamustine Hydrochloride</mesh_term>
    <mesh_term>Ofatumumab</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/NCT01691807
org study id: 113603
nct id: NCT01691807
lead sponsor: 
has dmc: No
The purpose of this study is to evaluate the potential drug-drug interactions between
      ofatumumab and bendamustine in subjects with previously untreated or relapsed indolent B-cell
      non-Hodgkin's lymphoma (NHL).
The purpose of this study is to evaluate the potential drug-drug interactions between
      ofatumumab and bendamustine in subjects with previously untreated or relapsed indolent B-cell
      non-Hodgkin's lymphoma (NHL). Ofatumumab and bendamustine will be administered alone and in
      combination in a two-arm, open-label study to evaluate the pharmacokinetic profile, safety,
      tolerability, and efficacy of ofatumumab and bendamustine.

      The primary objective of the study is to evaluate pharmacokinetic parameters of ofatumumab
      and bendamustine alone and in combination. Secondary objectives are to evaluate safety,
      tolerability, and efficacy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Pharmacokinetic measures of Cmax and Area Under the Curve by analysis of blood samples for the amount of each drug present at different timepoints.
time frame: 4 months
description: The amount of ofatumumab and bendamustine in the blood will be measured when given individually or together to obtain Cmax and Area Under the Curve. Bendamustine levels will be collected at Cycles 1 and 2: Predose, 0.25, 0.5, 0.75, 1 (end of infusion), 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, and 24 hours. Ofatumumab will be collected at Cycle 4: Predose, end of infusion, then 1, 2, 24, and 72 hours after end of infusion, then once each on Days 8, 15, and 22.
measure: Changes in vital signs and the number adverse events
time frame: 14 months
description: Changes in vital signs will be measured during the entire study to determine any effect on the subjects health. Also the recording of all adverse events that occur during the study will be collected for analysis.
measure: Measure the extent of the disease by CT scan or flow cytometry analysis
time frame: 14 months
description: Dimension measurement assessments by CT scan of disease will be collected at Screen, Cycle 5, 3 month follow up visit, and 6 month follow up visit. Flow cytometry measurements will be collected at Screen and Weeks 1, 2, 5, 13, 21, 41, and 53.
arm group label: Arm A
arm group type: Experimental
description: bendamustine and ofatumumab treatment of NHL
arm group label: Arm B
arm group type: Experimental
description: ofatumumab only treatment of NHL
intervention type: Drug
intervention name: ofatumumab
description: treatment for NHL
arm group label: Arm A
arm group label: Arm B
intervention type: Drug
intervention name: bendamustine
description: treatment for NHL
arm group label: Arm A
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, Non-Hodgkin
mesh term: Lymphoma, B-Cell
mesh term: Bendamustine Hydrochloride
mesh term: Ofatumumab