<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/NCT01701323</url>
  </required_header>
  <id_info>
    <org_study_id>2584</org_study_id>
    <secondary_id>NCI-2012-01724</secondary_id>
    <secondary_id>2584</secondary_id>
    <secondary_id>2584.00</secondary_id>
    <secondary_id>P30CA015704</secondary_id>
    <nct_id>NCT01701323</nct_id>
  </id_info>
  <brief_title>Expanded Cord Blood Cell Infusion Following Combination Chemotherapy in Younger Patients With Relapsed or Refractory Acute Myeloid Leukemia</brief_title>
  <official_title>Pilot Study Evaluating the Use of Ex Vivo Expanded Cord Blood Progenitors as Supportive Care Following Chemotherapy (FLAG) in Patients With AML or Acute Leukemia of Ambiguous Lineage</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nohla Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Fred Hutchinson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Nohla Therapeutics, Inc.</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>
      This pilot clinical trial studies infusion of expanded cord blood hematopoietic progenitor&#xD;
      cells following combination chemotherapy in treating younger patients with acute myeloid&#xD;
      leukemia that has relapsed or has not responded to treatment. Chemotherapy drugs work in&#xD;
      different ways to stop the growth of cancer cells, either by killing the cells, by stopping&#xD;
      them from dividing, or by stopping them from spreading. Chemotherapy also kills healthy&#xD;
      infection-fighting cells, increasing the risk of infection. The infusion of expanded cord&#xD;
      blood hematopoietic progenitor cells may be able to replace blood-forming cells that were&#xD;
      destroyed by chemotherapy. This cellular therapy may decrease the risk of infection following&#xD;
      chemotherapy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <start_date type="Actual">December 10, 2012</start_date>
  <completion_date type="Actual">May 10, 2018</completion_date>
  <primary_completion_date type="Actual">May 10, 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>Incidence of NCI CTCAE grade &gt; 3 infusional toxicities</measure>
    <time_frame>Up to 2 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrence of transfusion associated graft versus host disease</measure>
    <time_frame>Up to 2 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of platelet refractoriness in the presence of alloimmunization as a direct result of ex vivo expanded cord blood product infusion</measure>
    <time_frame>Up to 2 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of delayed marrow recovery</measure>
    <time_frame>Up to day 42</time_frame>
    <description>Failure to achieve ANC &gt;= 500 cells/µl by day 42 post treatment with marrow cellularity &lt; 5% and marrow blast count &lt; 5%.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Rate of treatment related mortality</measure>
    <time_frame>Up to 2 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to neutrophil recovery</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>ANC &gt;= 100 cells/ul and 500 cells/ul</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>In vivo persistence of ex vivo expanded cellular therapy</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Assessed by peripheral blood cell sorted deoxyribonucleic acid (DNA) chimerisms of the cluster of differentiation myeloid and lymphoid cell lineages as well as whole marrow chimerisms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient and infused expanded cord blood cells immune interaction</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Assessed by performing host-donor studies.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of NCI CTCAE grade 3 or 4 infections</measure>
    <time_frame>First 30 days following FLAG administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of NCI CTCAE grade &gt; 3 chemotherapy-related toxicity in the first 30 days following fludarabine phosphate, cytarabine, and filgrastim (FLAG) therapy</measure>
    <time_frame>First 30 days following FLAG administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of complete remission</measure>
    <time_frame>Up to 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Leukemia-free survival</measure>
    <time_frame>Up to 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Up to 2 years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">7</enrollment>
  <condition>Acute Leukemia of Ambiguous Lineage</condition>
  <condition>Acute Myeloid Leukemia</condition>
  <arm_group>
    <arm_group_label>Treatment (Ex-vivo expanded cord blood progenitors)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive filgrastim SC or IV on days 1-7, fludarabine phosphate IV QD over 30 minutes on days 2-6, cytarabine IV QD over 4 hours on days 2-6, and ex-vivo expanded cord blood progenitor cells IV over 30 minutes on day 8.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Ex-Vivo Expanded Cord Blood Progenitor Cell Infusion</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (Ex-vivo expanded cord blood progenitors)</arm_group_label>
    <other_name>NLA101</other_name>
    <other_name>Dilanubicel</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cytarabine</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (Ex-vivo expanded cord blood progenitors)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Filgrastim</intervention_name>
    <description>Given SC or IV</description>
    <arm_group_label>Treatment (Ex-vivo expanded cord blood progenitors)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fludarabine Phosphate</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (Ex-vivo expanded cord blood progenitors)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have a diagnosis of AML or acute leukemia of ambiguous lineage according&#xD;
             to World Health Organization (WHO) classification with &gt;= 5% of disease in bone marrow&#xD;
             (BM)&#xD;
&#xD;
          -  Recipients of prior allogeneic hematopoietic stem cell transplantation for AML or&#xD;
             acute leukemia of ambiguous lineage are eligible if they do not have graft-versus-host&#xD;
             disease (GVHD) or they have quiescent GVHD whether or not they are receiving&#xD;
             immunosuppressive therapy&#xD;
&#xD;
          -  Must have a Lansky or Karnofsky performance status of &gt;= 50; use Karnofsky for&#xD;
             patients &gt; 16 years of age and Lansky for patients =&lt; 16 years of age&#xD;
&#xD;
          -  Patients must have recovered from the acute toxicity of all prior chemotherapy&#xD;
&#xD;
          -  The following amounts of time must have elapsed prior to entry on study:&#xD;
&#xD;
               -  2 weeks from local radiation therapy (XRT)&#xD;
&#xD;
               -  8 weeks from prior craniospinal or if &gt; 50% of the pelvis has been irradiated&#xD;
&#xD;
               -  6 weeks must have elapsed if other bone marrow radiation has occurred&#xD;
&#xD;
          -  Adequate cardiac, renal, pulmonary, and hepatic function&#xD;
&#xD;
          -  Patient must have a life expectancy of at least 2 months&#xD;
&#xD;
          -  Females of childbearing potential must have a negative serum pregnancy test performed&#xD;
             within 7 days prior to the start of treatment&#xD;
&#xD;
          -  Females of childbearing potential and males should agree to use adequate contraception&#xD;
             (barrier method of birth control) prior to study entry and for the duration of study&#xD;
             participation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Recipients of prior allogeneic hematopoietic stem cell transplant (HSCT) with active&#xD;
             acute or chronic GVHD&#xD;
&#xD;
          -  Patients with history of Down's syndrome, Fanconi anemia or other known marrow failure&#xD;
             condition&#xD;
&#xD;
          -  Patients currently receiving other investigational drugs are not eligible&#xD;
&#xD;
          -  Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as&#xD;
             specified in the protocol with the exception of intrathecal chemotherapy; this&#xD;
             includes the tyrosine kinase inhibitor sorafenib which must not be initiated until&#xD;
             patient demonstrates count recovery&#xD;
&#xD;
          -  Patients with a systemic fungal, bacterial, viral, or other infection not controlled&#xD;
             despite appropriate antibiotics or other treatment; uncontrolled systemic infections&#xD;
             require infectious disease consultation for verification&#xD;
&#xD;
          -  Patients who are platelet refractory prior to initiation of protocol therapy&#xD;
&#xD;
          -  Pregnant or lactating patients&#xD;
&#xD;
          -  Any significant concurrent disease, illness, or psychiatric disorder that would&#xD;
             compromise patient safety or compliance, interfere with consent, study participation,&#xD;
             follow up, or interpretation of study results&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>30 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ann Dahlberg</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Emory University/Winship Cancer Institute</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>October 3, 2012</study_first_submitted>
  <study_first_submitted_qc>October 3, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 5, 2012</study_first_posted>
  <last_update_submitted>February 27, 2019</last_update_submitted>
  <last_update_submitted_qc>February 27, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 1, 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>Leukemia</mesh_term>
    <mesh_term>Leukemia, Myeloid</mesh_term>
    <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cytarabine</mesh_term>
    <mesh_term>Fludarabine</mesh_term>
    <mesh_term>Fludarabine phosphate</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/NCT01701323
org study id: 2584
secondary id: NCI-2012-01724
secondary id: 2584
secondary id: 2584.00
secondary id: P30CA015704
nct id: NCT01701323
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This pilot clinical trial studies infusion of expanded cord blood hematopoietic progenitor
      cells following combination chemotherapy in treating younger patients with acute myeloid
      leukemia that has relapsed or has not responded to treatment. Chemotherapy drugs 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. Chemotherapy also kills healthy
      infection-fighting cells, increasing the risk of infection. The infusion of expanded cord
      blood hematopoietic progenitor cells may be able to replace blood-forming cells that were
      destroyed by chemotherapy. This cellular therapy may decrease the risk of infection following
      chemotherapy.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of NCI CTCAE grade > 3 infusional toxicities
time frame: Up to 2 years
measure: Occurrence of transfusion associated graft versus host disease
time frame: Up to 2 years
measure: Incidence of platelet refractoriness in the presence of alloimmunization as a direct result of ex vivo expanded cord blood product infusion
time frame: Up to 2 years
measure: Incidence of delayed marrow recovery
time frame: Up to day 42
description: Failure to achieve ANC >= 500 cells/µl by day 42 post treatment with marrow cellularity < 5% and marrow blast count < 5%.
measure: Rate of treatment related mortality
time frame: Up to 2 years
measure: Time to neutrophil recovery
time frame: Up to 2 years
description: ANC >= 100 cells/ul and 500 cells/ul
measure: In vivo persistence of ex vivo expanded cellular therapy
time frame: Up to 2 years
description: Assessed by peripheral blood cell sorted deoxyribonucleic acid (DNA) chimerisms of the cluster of differentiation myeloid and lymphoid cell lineages as well as whole marrow chimerisms.
measure: Patient and infused expanded cord blood cells immune interaction
time frame: Up to 2 years
description: Assessed by performing host-donor studies.
measure: Incidence of NCI CTCAE grade 3 or 4 infections
time frame: First 30 days following FLAG administration
measure: Incidence of NCI CTCAE grade > 3 chemotherapy-related toxicity in the first 30 days following fludarabine phosphate, cytarabine, and filgrastim (FLAG) therapy
time frame: First 30 days following FLAG administration
measure: Rate of complete remission
time frame: Up to 2 years
measure: Leukemia-free survival
time frame: Up to 2 years
measure: Overall survival
time frame: Up to 2 years
arm group label: Treatment (Ex-vivo expanded cord blood progenitors)
arm group type: Experimental
description: Patients receive filgrastim SC or IV on days 1-7, fludarabine phosphate IV QD over 30 minutes on days 2-6, cytarabine IV QD over 4 hours on days 2-6, and ex-vivo expanded cord blood progenitor cells IV over 30 minutes on day 8.
intervention type: Biological
intervention name: Ex-Vivo Expanded Cord Blood Progenitor Cell Infusion
description: Given IV
arm group label: Treatment (Ex-vivo expanded cord blood progenitors)
other name: NLA101
other name: Dilanubicel
intervention type: Drug
intervention name: Cytarabine
description: Given IV
arm group label: Treatment (Ex-vivo expanded cord blood progenitors)
intervention type: Drug
intervention name: Filgrastim
description: Given SC or IV
arm group label: Treatment (Ex-vivo expanded cord blood progenitors)
intervention type: Drug
intervention name: Fludarabine Phosphate
description: Given IV
arm group label: Treatment (Ex-vivo expanded cord blood progenitors)
criteria: 
gender: All
minimum age: 6 Months
maximum age: 30 Years
healthy volunteers: No
last name: Ann Dahlberg
role: Principal Investigator
affiliation: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Cytarabine
mesh term: Fludarabine
mesh term: Fludarabine phosphate