<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/NCT02264873</url>
  </required_header>
  <id_info>
    <org_study_id>IRB201400612</org_study_id>
    <secondary_id>PEDS004</secondary_id>
    <nct_id>NCT02264873</nct_id>
  </id_info>
  <brief_title>Phase I, Dose Escalation Study of Decitabine</brief_title>
  <official_title>Minimizing Leukemia Relapse: A Phase I, Dose Escalation Study of Decitabine in High Risk Pediatric Leukemia Post Allogeneic Transplant</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Florida</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hyundai Hope On Wheels</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Florida</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>
      Decitabine is a hypomethylating agent that has shown significant anti-leukemic effect in&#xD;
      Myelodysplastic Syndrome (MDS) and Acute Myeloblastic Leukemia (AML). This study is based on&#xD;
      the hypothesis that Decitabine delivered after allo-hematopoietic stem cell transplant (HSCT)&#xD;
      in patients with leukemia will enhance disease control by the allogeneic immune system and&#xD;
      lead to a longer disease free survival. The study is designed to provide safety data of&#xD;
      low-dosing in the post-transplant setting.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Decitabine is a hypomethylating agent with significant anti-leukemic effect in MDS and AML.&#xD;
      Additionally, aberrant DNA methylation has been identified in high risk childhood ALL, and&#xD;
      therefore, DNA hypomethylating agents, such as decitabine, have been identified as&#xD;
      therapeutic agents. Moreover, decitabine has immunomodulatory effects by enhancement of class&#xD;
      I human leukocyte antigen (HLA) antigen expression on cancer cells, which increases their&#xD;
      susceptibility to immune surveillance mechanisms, such as graft-versus-leukemia effect of&#xD;
      donor cells in allogeneic transplantation and by augmentation of natural killer (NK), T and B&#xD;
      lymphocyte reactivity. We hypothesize that decitabine delivered after allo-HSCT in patients&#xD;
      with leukemia will enhance disease control by the allogeneic immune system and lead to a&#xD;
      longer disease free survival. However, a safety study is needed to determine appropriate&#xD;
      decitabine dosing in the post-transplant period. Low doses of decitabine are likely better&#xD;
      tolerated in the post-transplant setting given risks of myelosuppression. In addition, when&#xD;
      administered at lower doses, decitabine's hypomethylation effects are more pronounced in&#xD;
      relation to its pyrimidine analog cytotoxic effects. In this study low doses of decitabine&#xD;
      will be administered beginning 6 weeks to 100 days post-transplant. Measures of gene&#xD;
      methylation and immune reconstitution will be conducted to define biologically active doses.&#xD;
      Results from this trial will provide new clinical data regarding the effects of decitabine on&#xD;
      gene methylation and immunoreactivity, will establish a maximally tolerated dose in the&#xD;
      post-transplant setting, will define biologically active doses, and will serve as a basis for&#xD;
      future efficacy trials.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">September 18, 2018</completion_date>
  <primary_completion_date type="Actual">October 2016</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>Maximum Tolerated Dose as a Measure of Safety and Tolerability</measure>
    <time_frame>3 months</time_frame>
    <description>This is a dose escalation study of decitabine maintenance therapy after allo-HSCT for the maximally tolerated dose in pediatric patients without adverse events.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse Event Profile After Single Cycle Decitabine Post Transplant</measure>
    <time_frame>6 months</time_frame>
    <description>The adverse events will be graded using the NCI Scale after one cycle of decitabine maintenance therapy intravenously. Grade 1 and 2 are unexpected and expect but unlikely related or unrelated; Grade 3 unexpected with hospitalization within 10 calendar days or possibly, probable related and without hospitalization; Grade 3 expected with hospitalization within 10 days or without hospitalization; Grade 4 and 5 Unexpected and Expected 24-hours to 5 days unlikely, unrelated, possible, probable, definite.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Grade 3 Adverse Events after Decitabine</measure>
    <time_frame>6 months</time_frame>
    <description>To estimate the incidences of ≥ grade 3 adverse events, infections, need for transfusions, treatment related mortality (TRM), and incidence and severity of graft vs host disease (GVHD) after initiation of decitabine post-HSCT. The grading will be done with the NCI Scale Grade 3 unexpected with hospitalization within 10 calendar days or possibly, probable related and without hospitalization; Grade 3 expected with hospitalization within 10 days or without hospitalization.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">3</enrollment>
  <condition>Leukemia, Lymphoblastic, Acute</condition>
  <condition>Leukemia, Myeloid Acute</condition>
  <condition>Hematopoetic Myelodysplasia</condition>
  <arm_group>
    <arm_group_label>Decitabine</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>This is a 3+3 design of dose escalation</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Decitabine</intervention_name>
    <description>Dose escalation starting at 5 mg, and increasing by 2.5 mg to a Dose Level of 12.5 mg qd x 3 days.</description>
    <arm_group_label>Decitabine</arm_group_label>
    <other_name>Decitabine, Dacogen</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age: greater than 1 and less than 31 years of age;&#xD;
&#xD;
          -  Diagnosis: history of ALL, AML or MDS, currently in a complete remission (CR)&#xD;
             following allo-HSCT (bone marrow leukemic blasts less than 5% by morphology), with&#xD;
             high risk features including:&#xD;
&#xD;
          -  Status post allogeneic HSCT&#xD;
&#xD;
          -  GVHD prophylaxis:&#xD;
&#xD;
          -  Karnofsky or Lansky performance scores more than 50%. Karnofsky scores will be used&#xD;
             for patients &gt; 16 years of age and Lansky scores for patients ≤ 16 years of age;&#xD;
&#xD;
          -  Platelet count ≥ 50,000 (untransfused);&#xD;
&#xD;
          -  Absolute neutrophil count ≥ 1000; and;&#xD;
&#xD;
          -  Hemoglobin ≥ 8 g/dL (un-transfused);&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Progressive disease;&#xD;
&#xD;
          -  Philadelphia chromosome positive ALL (these patients receive tyrosine kinase inhibitor&#xD;
             posttransplant);&#xD;
&#xD;
          -  Known hypersensitivity to any components of decitabine;&#xD;
&#xD;
          -  Uncontrolled grade 3-4 graft versus host disease;&#xD;
&#xD;
          -  Uncontrolled infection;&#xD;
&#xD;
          -  Serum creatinine &gt; 2 mg/dL or glomerular filtration rate (GFR) less than 60&#xD;
             mL/min/1.73m2 ;&#xD;
&#xD;
          -  Alanine Aminotransferase (ALT) greater than 3 times normal or serum total bilirubin&#xD;
             greater than 2 mg/dL;&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>30 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paul Castillo, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Florida</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UF Health Shands Hospital</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32610</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>October 6, 2014</study_first_submitted>
  <study_first_submitted_qc>October 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 15, 2014</study_first_posted>
  <last_update_submitted>October 12, 2018</last_update_submitted>
  <last_update_submitted_qc>October 12, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 15, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Relapse</keyword>
  <keyword>Autologous stem cell transplant</keyword>
  <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>Preleukemia</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Myelodysplastic Syndromes</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Decitabine</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/NCT02264873
org study id: IRB201400612
secondary id: PEDS004
nct id: NCT02264873
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Decitabine is a hypomethylating agent that has shown significant anti-leukemic effect in
      Myelodysplastic Syndrome (MDS) and Acute Myeloblastic Leukemia (AML). This study is based on
      the hypothesis that Decitabine delivered after allo-hematopoietic stem cell transplant (HSCT)
      in patients with leukemia will enhance disease control by the allogeneic immune system and
      lead to a longer disease free survival. The study is designed to provide safety data of
      low-dosing in the post-transplant setting.
Decitabine is a hypomethylating agent with significant anti-leukemic effect in MDS and AML.
      Additionally, aberrant DNA methylation has been identified in high risk childhood ALL, and
      therefore, DNA hypomethylating agents, such as decitabine, have been identified as
      therapeutic agents. Moreover, decitabine has immunomodulatory effects by enhancement of class
      I human leukocyte antigen (HLA) antigen expression on cancer cells, which increases their
      susceptibility to immune surveillance mechanisms, such as graft-versus-leukemia effect of
      donor cells in allogeneic transplantation and by augmentation of natural killer (NK), T and B
      lymphocyte reactivity. We hypothesize that decitabine delivered after allo-HSCT in patients
      with leukemia will enhance disease control by the allogeneic immune system and lead to a
      longer disease free survival. However, a safety study is needed to determine appropriate
      decitabine dosing in the post-transplant period. Low doses of decitabine are likely better
      tolerated in the post-transplant setting given risks of myelosuppression. In addition, when
      administered at lower doses, decitabine's hypomethylation effects are more pronounced in
      relation to its pyrimidine analog cytotoxic effects. In this study low doses of decitabine
      will be administered beginning 6 weeks to 100 days post-transplant. Measures of gene
      methylation and immune reconstitution will be conducted to define biologically active doses.
      Results from this trial will provide new clinical data regarding the effects of decitabine on
      gene methylation and immunoreactivity, will establish a maximally tolerated dose in the
      post-transplant setting, will define biologically active doses, and will serve as a basis for
      future efficacy trials.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose as a Measure of Safety and Tolerability
time frame: 3 months
description: This is a dose escalation study of decitabine maintenance therapy after allo-HSCT for the maximally tolerated dose in pediatric patients without adverse events.
measure: Adverse Event Profile After Single Cycle Decitabine Post Transplant
time frame: 6 months
description: The adverse events will be graded using the NCI Scale after one cycle of decitabine maintenance therapy intravenously. Grade 1 and 2 are unexpected and expect but unlikely related or unrelated; Grade 3 unexpected with hospitalization within 10 calendar days or possibly, probable related and without hospitalization; Grade 3 expected with hospitalization within 10 days or without hospitalization; Grade 4 and 5 Unexpected and Expected 24-hours to 5 days unlikely, unrelated, possible, probable, definite.
measure: Grade 3 Adverse Events after Decitabine
time frame: 6 months
description: To estimate the incidences of ≥ grade 3 adverse events, infections, need for transfusions, treatment related mortality (TRM), and incidence and severity of graft vs host disease (GVHD) after initiation of decitabine post-HSCT. The grading will be done with the NCI Scale Grade 3 unexpected with hospitalization within 10 calendar days or possibly, probable related and without hospitalization; Grade 3 expected with hospitalization within 10 days or without hospitalization.
arm group label: Decitabine
arm group type: Other
description: This is a 3+3 design of dose escalation
intervention type: Drug
intervention name: Decitabine
description: Dose escalation starting at 5 mg, and increasing by 2.5 mg to a Dose Level of 12.5 mg qd x 3 days.
arm group label: Decitabine
other name: Decitabine, Dacogen
criteria: 
gender: All
minimum age: 1 Year
maximum age: 30 Years
healthy volunteers: No
last name: Paul Castillo, MD
role: Principal Investigator
affiliation: University of Florida
facility: 
country: United States
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Preleukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Myelodysplastic Syndromes
mesh term: Decitabine