<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/NCT01680796</url>
  </required_header>
  <id_info>
    <org_study_id>CTKI258AU012T</org_study_id>
    <nct_id>NCT01680796</nct_id>
  </id_info>
  <brief_title>Dovitinib Combined With Bortezomib and Dexamethasone for Relapsed/Refractory Multiple Myeloma</brief_title>
  <official_title>Phase I, Open Label, Clinical Study to Determine the Maximum Tolerated Dose (MTD) of Oral Dovitinib (TKI258) When Given in Combination With Bortezomib and Dexamethasone for the Treatment of Relapsed/Refractory Multiple Myeloma Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Florida</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Florida</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open-label phase I study in which dovitinib is given in combination with&#xD;
      bortezomib and dexamethasone. Dovitinib dose escalation is planned in order to determine its&#xD;
      maximum tolerated dose when given in this combination.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    The target drug, dovitinib, failed as a single agent in prior studies in patients with heavily&#xD;
    treated multiple myeloma.&#xD;
  </why_stopped>
  <start_date>February 2013</start_date>
  <completion_date type="Actual">February 2013</completion_date>
  <primary_completion_date type="Actual">February 2013</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>Evaluate the safety and dose-limiting toxicity of treatment with dovitinib in combination with bortezomib/ dexamethasone.</measure>
    <time_frame>Treatment Cycle 1 (three weeks) for each participant.</time_frame>
    <description>Determination of the maximum tolerated dose of dovitinib will be based on Treatment Cycle 1 safety data for all subjects for whom all safety assessments during Treatment Cycle 1, as well as the pre-dosing safety assessments performed on Study Day 1 of Treatment Cycle 2, are completed and who do not receive alternate anti-neoplastic therapies during that period.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To assess the overall response rate for the combination dovitinib/bortezomib/ dexamethasone in patients receiving at least 4 cycles of therapy.</measure>
    <time_frame>Participants will be followed for up to one year.</time_frame>
    <description>Starting with Treatment Cycle 2, response to treatment will be determined during each treatment cycle (Stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), and Stable Disease (SD)).</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Other Secondary Efficacy Objectives</measure>
    <time_frame>Up to 10 years</time_frame>
    <description>Participants will be evaluated for time to first response, duration of response, time to best response, and time to disease progression.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Active Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dovitinib will be given at up to four different dose levels beginning with dose level 1 on a 5 days on/2 days off dosing schedule of each 21-day cycle.&#xD;
Bortezomib will be given at two different dose levels intravenously on Days 1 and 8 of each 21-day cycle.&#xD;
Dexamethasone will be given orally on Days 1, 2, 8, and 9 of each 21-day cycle.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dovitinib</intervention_name>
    <description>Dose Level 0: 200 mg daily&#xD;
Dose Level 1: 300 mg daily&#xD;
Dose Level 2: 300 mg daily&#xD;
Dose Level 3: 400 mg daily&#xD;
Dose Level 4: 500 mg daily</description>
    <arm_group_label>Active Treatment</arm_group_label>
    <other_name>TKI258</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bortezomib</intervention_name>
    <description>Dose Level 0: 1.3 mg/m2 IV on days 1 and 8&#xD;
Dose Level 1: 1.3 mg/m2 IV on days 1 and 8&#xD;
Dose Level 2: 1.6 mg/m2 IV on days 1 and 8&#xD;
Dose Level 3: 1.6 mg/m2 IV on days 1 and 8&#xD;
Dose Level 4: 1.6 mg/m2 IV on days 1 and 8</description>
    <arm_group_label>Active Treatment</arm_group_label>
    <other_name>Velcade</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>Dexamethasone 20 mg will be given orally on Days 1, 2, 8, and 9 of each 21-day cycle.</description>
    <arm_group_label>Active Treatment</arm_group_label>
    <other_name>Decadron</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of multiple myeloma&#xD;
&#xD;
          -  Karnofsky performance status ≥ 70&#xD;
&#xD;
          -  Age ≥ 18 years old&#xD;
&#xD;
          -  Evidence of relapsed or refractory disease as documented from the prior treatment&#xD;
             history&#xD;
&#xD;
          -  Have received at least 1, but not more than 3, prior treatment regimens for multiple&#xD;
             myeloma including chemotherapy, autologous stem cell transplantation, immunotherapy,&#xD;
             or other investigational agents. Prior allogeneic stem cell transplant and prior&#xD;
             therapy with bortezomib (with no evidence of disease resistance to bortezomib) are&#xD;
             permitted.&#xD;
&#xD;
          -  Last dose of chemotherapy no less than 4 weeks prior to receipt of study medication&#xD;
             and have recovered from the side effects of such therapy&#xD;
&#xD;
          -  Last dose of biological therapy, or antibody, or other investigational agents, no less&#xD;
             than 4 weeks prior to receipt of study medication&#xD;
&#xD;
          -  Subjects must have the following laboratory values:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1.5 x 109/L&#xD;
&#xD;
               -  Platelets ≥ 100 x 109/L&#xD;
&#xD;
               -  Hemoglobin (Hgb) &gt; 9 g/dL&#xD;
&#xD;
               -  Serum total bilirubin: ≤ 1.5 x ULN&#xD;
&#xD;
               -  ALT and AST ≤ 3.0 x ULN&#xD;
&#xD;
               -  Serum creatinine ≤ 1.5 x ULN&#xD;
&#xD;
          -  Willing and able to undergo bone marrow aspirates as per protocol, with/without bone&#xD;
             marrow biopsy according to the study center's practice. - Life expectancy of ≥ 12&#xD;
             weeks&#xD;
&#xD;
          -  All subjects (male and female) of child bearing potential must agree to use adequate&#xD;
             contraceptive methods.&#xD;
&#xD;
          -  Negative serum pregnancy test (≤ 72 hours prior to the first dosing of dovitinib) in&#xD;
             all women of childbearing potential&#xD;
&#xD;
          -  Subjects who give a written informed consent obtained according to local guidelines&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with CNS (central nervous system) disease&#xD;
&#xD;
          -  Subjects with another primary malignancy within 3 years prior to starting study drug,&#xD;
             with the exception of adequately treated in-situ carcinoma of the uterine cervix, or&#xD;
             skin cancer&#xD;
&#xD;
          -  Subjects who have received the last administration of an anticancer therapy including&#xD;
             chemotherapy, immunotherapy, hormonal therapy and monoclonal antibodies (but excluding&#xD;
             nitrosurea, mitomycin-C, targeted therapy and radiation) ≤ 4 weeks prior to starting&#xD;
             study drug, or who have not recovered from the side effects of such therapy&#xD;
&#xD;
          -  Subjects who have had radiotherapy ≤ 4 weeks prior to starting study drug, or ≤ 2&#xD;
             weeks prior to starting study drug in the case of localized radiotherapy (e.g. for&#xD;
             analgesic purpose or for lytic lesions at risk of fracture), or who have not recovered&#xD;
             from radiotherapy toxicities&#xD;
&#xD;
          -  Subjects who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or&#xD;
             intra-pelvic), open biopsy or significant traumatic injury ≤ 4 weeks prior to starting&#xD;
             study drug, or subjects who have had minor procedures, percutaneous biopsies or&#xD;
             placement of vascular access device ≤ 1 week prior to starting study drug, or who have&#xD;
             not recovered from side effects of such procedure or injury&#xD;
&#xD;
          -  Subjects with any of the following concurrent severe and/or uncontrolled medical&#xD;
             conditions which could compromise participation in the study:&#xD;
&#xD;
               -  Impaired cardiac function or clinically significant cardiac diseases, including&#xD;
                  any of the following:&#xD;
&#xD;
                    1. History or presence of serious uncontrolled ventricular arrhythmias&#xD;
&#xD;
                    2. Clinically significant resting bradycardia&#xD;
&#xD;
                    3. LVEF assessed by 2-D echocardiogram (ECHO) &lt; 50% or lower limit of normal&#xD;
                       (whichever is higher) or multiple gated acquisition scan (MUGA) &lt; 45% or&#xD;
                       lower limit of normal (whichever is higher).&#xD;
&#xD;
                    4. Any of the following within 6 months prior to starting study drug:&#xD;
                       myocardial infarction (MI), severe/unstable angina, Coronary Artery Bypass&#xD;
                       Graft (CABG), Congestive Heart Failure (CHF), Cerebrovascular Accident&#xD;
                       (CVA), Transient Ischemic Attack (TIA), Pulmonary Embolism (PE)&#xD;
&#xD;
                    5. Uncontrolled hypertension defined by a SBP ≥ 160 mm Hg and/or DBP ≥ 100 mm&#xD;
                       Hg, with or without anti-hypertensive medication(s),&#xD;
&#xD;
               -  Impairment of gastrointestinal (GI) function or GI disease that may significantly&#xD;
                  alter the absorption of dovitinib (e.g. ulcerative diseases, uncontrolled nausea,&#xD;
                  vomiting, diarrhea, malabsorption syndrome, or small bowel resection),&#xD;
&#xD;
               -  Cirrhosis, chronic active hepatitis or chronic persistent hepatitis,&#xD;
&#xD;
               -  Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is&#xD;
                  not mandatory),&#xD;
&#xD;
               -  Subjects who are currently receiving anticoagulation treatment with therapeutic&#xD;
                  doses of warfarin,&#xD;
&#xD;
               -  Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g.&#xD;
                  active or uncontrolled infection, uncontrolled diabetes) that could cause&#xD;
                  unacceptable safety risks or compromise compliance with the protocol&#xD;
&#xD;
          -  Pregnant or breast-feeding women&#xD;
&#xD;
          -  Women of child-bearing potential, who are biologically able to conceive, not willing&#xD;
             to employ two forms of highly effective contraception&#xD;
&#xD;
          -  Fertile males not willing to use contraception&#xD;
&#xD;
          -  Subject has a known hypersensitivity to bortezomib, or known Grade ≥ 2&#xD;
             bortezomib-related neuropathy&#xD;
&#xD;
          -  Subjects unwilling or unable to comply with the protocol&#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>Jan S. Moreb, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Florida</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <verification_date>February 2013</verification_date>
  <study_first_submitted>August 29, 2012</study_first_submitted>
  <study_first_submitted_qc>September 4, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 7, 2012</study_first_posted>
  <last_update_submitted>February 18, 2013</last_update_submitted>
  <last_update_submitted_qc>February 18, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 20, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Multiple Myeloma</keyword>
  <keyword>Relapsed Multiple Myeloma</keyword>
  <keyword>Refractory Multiple Myeloma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexamethasone</mesh_term>
    <mesh_term>Bortezomib</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/NCT01680796
org study id: CTKI258AU012T
nct id: NCT01680796
lead sponsor: 
collaborator: 
has dmc: Yes
This is an open-label phase I study in which dovitinib is given in combination with
      bortezomib and dexamethasone. Dovitinib dose escalation is planned in order to determine its
      maximum tolerated dose when given in this combination.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Evaluate the safety and dose-limiting toxicity of treatment with dovitinib in combination with bortezomib/ dexamethasone.
time frame: Treatment Cycle 1 (three weeks) for each participant.
description: Determination of the maximum tolerated dose of dovitinib will be based on Treatment Cycle 1 safety data for all subjects for whom all safety assessments during Treatment Cycle 1, as well as the pre-dosing safety assessments performed on Study Day 1 of Treatment Cycle 2, are completed and who do not receive alternate anti-neoplastic therapies during that period.
measure: To assess the overall response rate for the combination dovitinib/bortezomib/ dexamethasone in patients receiving at least 4 cycles of therapy.
time frame: Participants will be followed for up to one year.
description: Starting with Treatment Cycle 2, response to treatment will be determined during each treatment cycle (Stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), and Stable Disease (SD)).
measure: Other Secondary Efficacy Objectives
time frame: Up to 10 years
description: Participants will be evaluated for time to first response, duration of response, time to best response, and time to disease progression.
arm group label: Active Treatment
arm group type: Experimental
description: Dovitinib will be given at up to four different dose levels beginning with dose level 1 on a 5 days on/2 days off dosing schedule of each 21-day cycle.
Bortezomib will be given at two different dose levels intravenously on Days 1 and 8 of each 21-day cycle.
Dexamethasone will be given orally on Days 1, 2, 8, and 9 of each 21-day cycle.
intervention type: Drug
intervention name: Dovitinib
description: Dose Level 0: 200 mg daily
Dose Level 1: 300 mg daily
Dose Level 2: 300 mg daily
Dose Level 3: 400 mg daily
Dose Level 4: 500 mg daily
arm group label: Active Treatment
other name: TKI258
intervention type: Drug
intervention name: Bortezomib
description: Dose Level 0: 1.3 mg/m2 IV on days 1 and 8
Dose Level 1: 1.3 mg/m2 IV on days 1 and 8
Dose Level 2: 1.6 mg/m2 IV on days 1 and 8
Dose Level 3: 1.6 mg/m2 IV on days 1 and 8
Dose Level 4: 1.6 mg/m2 IV on days 1 and 8
arm group label: Active Treatment
other name: Velcade
intervention type: Drug
intervention name: Dexamethasone
description: Dexamethasone 20 mg will be given orally on Days 1, 2, 8, and 9 of each 21-day cycle.
arm group label: Active Treatment
other name: Decadron
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jan S. Moreb, MD
role: Principal Investigator
affiliation: University of Florida
country: United States
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Dexamethasone
mesh term: Bortezomib