<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/NCT04448834</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00104913</org_study_id>
    <nct_id>NCT04448834</nct_id>
  </id_info>
  <brief_title>Blincyto Amgen Acrotech BioPharma PH2 Blincyto Marqibo R/R Philadelphi CD19+ ALL</brief_title>
  <official_title>A Phase 2 Single Arm, Multicenter Trial to Evaluate the Efficacy of the BiTE® Antibody Blinatumomab (Blincyto) and Vincristine Sulfate Liposomal Injection (Marqibo) in Adult Subjects With Relapsed/Refractory Philadelphia Negative CD19+ Acute Lymphoblastic Leukemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dorothy Sipkins, MD, PhD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Amgen</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Acrotech Biopharma Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Hypotheses: The Investigator hypothesizes that targeting ALL cells with 2 different&#xD;
      modalities, ie liposomal vincristine sulfate as a microtubule inhibitor and blinatumomab as a&#xD;
      BITE immuno-oncology therapy, will have at least additive benefits and allow an effective,&#xD;
      safe therapeutic option for patients. Further, the Investigator hypothesizes that the&#xD;
      combination will result in a high rate of response and thus allow enhanced immunologic&#xD;
      recovery.&#xD;
&#xD;
      Primary Objectives To evaluate whether the combination will result in a median&#xD;
      progression-free survival (PFS) of at least 1 year.&#xD;
&#xD;
      To evaluate if the complete remission/complete remission with incomplete hematological&#xD;
      recovery (CR/CRi*) rate is ≧ 75% following 2 cycles in adult subjects with R/R Ph- ALL and&#xD;
      duration of remission Secondary Objectives To evaluate the rate of Minimal Residual Disease&#xD;
      (MRD) and duration To evaluate the proportion of patients who are able to progress to&#xD;
      allogeneic transplantation To evaluate the safety of blinatumomab and liposomal vincristine&#xD;
      sulfate in combination To evaluate the effect of the combination and response on measures of&#xD;
      immune reconstitution&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Study not moving forward&#xD;
  </why_stopped>
  <start_date type="Anticipated">January 2022</start_date>
  <completion_date type="Anticipated">June 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">June 1, 2023</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>Progression-free survival (PFS)</measure>
    <time_frame>At 1 year</time_frame>
    <description>patient report</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Complete remission/complete remission with incomplete hematological recovery (CR/CRi*) rate</measure>
    <time_frame>End of Cycle 2 (1 cycle is 6 weeks in duration)</time_frame>
    <description>lab reports</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Minimal Residual Disease (MRD) and duration</measure>
    <time_frame>End of Cycle 2 (1 cycle is 6 weeks in duration)</time_frame>
    <description>Flow Measurement</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimal Residual Disease (MRD) and duration</measure>
    <time_frame>End of Therapy (up to 58 weeks)</time_frame>
    <description>Flow Measurement</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients able to progress to allogeneic transplantation</measure>
    <time_frame>End of study (up to 58 weeks)</time_frame>
    <description>Investigator reported</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety of blinatumomab and liposomal vincristine sulfate in combination, as measured by rate of toxicity</measure>
    <time_frame>Through all cycles of therapy (up to 58 weeks)</time_frame>
    <description>Investigator report of toxicities</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immune reconstitution, as measured by the immune reconstitution panel</measure>
    <time_frame>End of study (up to 58 weeks)</time_frame>
    <description>immune reconstitution panel</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>B-cell Acute Lymphoblastic Leukemia</condition>
  <arm_group>
    <arm_group_label>Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single cycle of blinatumomab which includes 4 weeks of CIVI of blinatumomab followed by a 2 week treatment free interval</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Blinatumomab</intervention_name>
    <description>liposomal vincristine 2.25 mg/m2 weekly x 3 per cycle (weeks 3-5 in cycle 1 and 2-4 in subsequent cycles)</description>
    <arm_group_label>Treatment</arm_group_label>
    <other_name>liposomal vincristine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with Ph-, CD19+ ALL, with any of the following:&#xD;
&#xD;
          -  Relapsed or refractory to at least 2 prior regimens ≥ 5% blasts in the bone marrow or&#xD;
             peripheral blood or persistent extranodal/marrow site (such as skin).&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2&#xD;
&#xD;
          -  Age ≥ 18 years of age, at the time of informed consent.&#xD;
&#xD;
          -  Subject has provided informed consent. Those unable to provide consent for themselves&#xD;
             will not be eligible.&#xD;
&#xD;
          -  Pts may have been exposed to either agent in the past if they had at least 6 months of&#xD;
             response from start of therapy AND it has been at least 6 months since their last dose&#xD;
             of either agent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of malignancy other than ALL within 3 years prior to start of&#xD;
             protocol-required therapy with the exception of:&#xD;
&#xD;
          -  Malignancy treated with curative intent and with no known active disease present for 2&#xD;
             years before enrollment and felt to be at low risk for recurrence by the treating&#xD;
             physician&#xD;
&#xD;
          -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of&#xD;
             disease&#xD;
&#xD;
          -  Adequately treated cervical carcinoma in situ without evidence of disease&#xD;
&#xD;
          -  Adequately treated breast ductal carcinoma in situ without evidence of disease&#xD;
&#xD;
          -  Prostatic cancer without evidence of progression for 1 year.&#xD;
&#xD;
          -  History or presence of clinically relevant CNS pathology as adult seizures, recent&#xD;
             stroke (within 1 year), severe brain injuries, Parkinson's disease, psychosis&#xD;
&#xD;
          -  With the exception of CNS leukemia that is well controlled with therapy prior to&#xD;
             enrolling on this study. A negative CNS evaluation for active disease is required&#xD;
             within 3 months of enrollment in those with prior history within one year of active&#xD;
             CNS disease .&#xD;
&#xD;
          -  Current severe autoimmune disease or history of autoimmune disease with potential CNS&#xD;
             involvement such as lupus, sjogren's, psoriasis, multiple sclerosis, wegener's&#xD;
             granulomatosis.&#xD;
&#xD;
          -  Allogeneic HSCT within 12 weeks prior to start of blinatumomab/marqibo&#xD;
&#xD;
          -  Any active acute Graft-versus-Host Disease (GvHD) grade 2 to grade 4 according to the&#xD;
             Glucksberg criteria or active chronic GvHD requiring systemic treatment of more than&#xD;
             10 mg prednisone daily (or equivalent)&#xD;
&#xD;
          -  Cancer chemotherapy or immunotherapy within 2 weeks prior to start of&#xD;
             blinatumomab/marqibo. Administration of dexamethasone and hydrea permitted within the&#xD;
             21 day screening period.&#xD;
&#xD;
        Subject received prior anti-CD19 therapy ARE eligible however if they received prior&#xD;
        blinatumomab, however they are ineligible if they did not have a response to it lasting at&#xD;
        least 6 months; also they are ineligible if they had exposure to blinatumomab within 6&#xD;
        months of starting therapy on this study.&#xD;
&#xD;
          -  Abnormal screening laboratory values as defined below:&#xD;
&#xD;
          -  AST (SGOT) and/or ALT (SGPT) and/or alkaline phosphatase ≥ 5 x upper limit of normal&#xD;
             (ULN)&#xD;
&#xD;
          -  Total bilirubin ≥ 3 x ULN (unless related to Gilbert´s or Meulengracht disease)&#xD;
&#xD;
          -  Creatinine ≥ 3 ULN or creatinine clearance &lt; 40 mL/min (calculated)&#xD;
&#xD;
          -  Known infection with human immunodeficiency virus (HIV) or chronic active infection&#xD;
             with hepatitis B virus (PCR positive) or hepatitis C virus (PCR positive).&#xD;
&#xD;
          -  Subject is pregnant or breast feeding&#xD;
&#xD;
          -  Woman of childbearing potential and is not willing to use 2 highly effective methods&#xD;
             of contraception while receiving blinatumomab/marqibo and for an additional 3 months&#xD;
             after the last dose of protocol-specified therapy&#xD;
&#xD;
          -  Male who has a female partner of childbearing potential, and is not willing to use 2&#xD;
             highly effective forms of contraception for at least an additional 3 months after the&#xD;
             last dose of protocol-specified therapy&#xD;
&#xD;
          -  Male who has a pregnant partner, and is not willing to use a condom during sexual&#xD;
             activity for 3 months after the last dose of protocol-specified therapy&#xD;
&#xD;
          -  Currently receiving treatment in another investigational device or drug study or less&#xD;
             than 30 days since ending treatment on another investigational device or drug&#xD;
             study(s). The 30 days is calculated from day 1 of blinatumomab treatment.&#xD;
&#xD;
          -  Subject has known severe sensitivity to immunoglobulins or any of the products or&#xD;
             components to be administered during dosing.&#xD;
&#xD;
          -  History or evidence of any other clinically significant disorder, condition or disease&#xD;
             (with the exception of those outlined above) that, in the opinion of the Investigator,&#xD;
             would pose a risk to subject safety or interfere with the study evaluation, procedures&#xD;
             or completion.&#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>Dorothy Sipkins, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Moffitt Cancer Center</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novant Health Cancer Institute and Innovation Center</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>June 22, 2020</study_first_submitted>
  <study_first_submitted_qc>June 24, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 26, 2020</study_first_posted>
  <last_update_submitted>February 14, 2022</last_update_submitted>
  <last_update_submitted_qc>February 14, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Duke University</investigator_affiliation>
    <investigator_full_name>Dorothy Sipkins, MD, PhD</investigator_full_name>
    <investigator_title>Instructor in the Department of Medicine</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Leukemia, Lymphoid</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vincristine</mesh_term>
    <mesh_term>Blinatumomab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04448834
org study id: Pro00104913
nct id: NCT04448834
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Hypotheses: The Investigator hypothesizes that targeting ALL cells with 2 different
      modalities, ie liposomal vincristine sulfate as a microtubule inhibitor and blinatumomab as a
      BITE immuno-oncology therapy, will have at least additive benefits and allow an effective,
      safe therapeutic option for patients. Further, the Investigator hypothesizes that the
      combination will result in a high rate of response and thus allow enhanced immunologic
      recovery.

      Primary Objectives To evaluate whether the combination will result in a median
      progression-free survival (PFS) of at least 1 year.

      To evaluate if the complete remission/complete remission with incomplete hematological
      recovery (CR/CRi*) rate is ≧ 75% following 2 cycles in adult subjects with R/R Ph- ALL and
      duration of remission Secondary Objectives To evaluate the rate of Minimal Residual Disease
      (MRD) and duration To evaluate the proportion of patients who are able to progress to
      allogeneic transplantation To evaluate the safety of blinatumomab and liposomal vincristine
      sulfate in combination To evaluate the effect of the combination and response on measures of
      immune reconstitution
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-free survival (PFS)
time frame: At 1 year
description: patient report
measure: Complete remission/complete remission with incomplete hematological recovery (CR/CRi*) rate
time frame: End of Cycle 2 (1 cycle is 6 weeks in duration)
description: lab reports
measure: Minimal Residual Disease (MRD) and duration
time frame: End of Cycle 2 (1 cycle is 6 weeks in duration)
description: Flow Measurement
measure: Minimal Residual Disease (MRD) and duration
time frame: End of Therapy (up to 58 weeks)
description: Flow Measurement
measure: Proportion of patients able to progress to allogeneic transplantation
time frame: End of study (up to 58 weeks)
description: Investigator reported
measure: Safety of blinatumomab and liposomal vincristine sulfate in combination, as measured by rate of toxicity
time frame: Through all cycles of therapy (up to 58 weeks)
description: Investigator report of toxicities
measure: Immune reconstitution, as measured by the immune reconstitution panel
time frame: End of study (up to 58 weeks)
description: immune reconstitution panel
arm group label: Treatment
arm group type: Experimental
description: A single cycle of blinatumomab which includes 4 weeks of CIVI of blinatumomab followed by a 2 week treatment free interval
intervention type: Drug
intervention name: Blinatumomab
description: liposomal vincristine 2.25 mg/m2 weekly x 3 per cycle (weeks 3-5 in cycle 1 and 2-4 in subsequent cycles)
arm group label: Treatment
other name: liposomal vincristine
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Dorothy Sipkins, MD
role: Principal Investigator
affiliation: Duke University
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Duke University
investigator full name: Dorothy Sipkins, MD, PhD
investigator title: Instructor in the Department of Medicine
mesh term: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Lymphoid
mesh term: Vincristine
mesh term: Blinatumomab
sharing ipd: No