<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/NCT01685515</url>
  </required_header>
  <id_info>
    <org_study_id>CASE 10Z11</org_study_id>
    <nct_id>NCT01685515</nct_id>
  </id_info>
  <brief_title>Study of Decitabine and Tetrahydrouridine (THU) in Patients With Sickle Cell Disease</brief_title>
  <official_title>Phase 1 Study of Oral Decitabine and Tetrahydrouridine (THU) in Patients With High Risk Sickle Cell Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yogen Saunthararajah</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Illinois at Chicago</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>The Cleveland Clinic</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purposes of this study are to observe if oral tetrahydrouridine and decitabine can&#xD;
      increase fetal hemoglobin levels and improve the symptoms of sickle cell disease, and to&#xD;
      monitor how patient's bodies react to oral tetrahydrouridine and decitabine.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purposes of this study are to observe if oral tetrahydrouridine and decitabine can&#xD;
      increase fetal hemoglobin levels and improve the symptoms of sickle cell disease, and to&#xD;
      monitor how patient's bodies react to oral tetrahydrouridine and decitabine. The overall&#xD;
      purpose is to develop disease modifying treatment for sickle cell disease that is less&#xD;
      cytotoxic than the current standard of care, and which can directly and more efficiently&#xD;
      reactivate fetal hemoglobin levels. The hypothesis is that patients treated with oral&#xD;
      tetrahydrouridine and decitabine will have the same chance of severe non-hematologic&#xD;
      toxicities as the placebo group. The primary end-point is ≥ grade 3 non-hematologic toxicity.&#xD;
      The investigators' hypothesis is that patients in the treatment groups receiving oral&#xD;
      THU-decitabine 2X/week over 8 weeks (n=15) will be equivalent to placebo group (n=10) with&#xD;
      regards to the chance of ≥ grade 3 non-hematologic toxicity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">June 2018</completion_date>
  <primary_completion_date type="Actual">June 2018</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>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Non-hematologic toxicity</measure>
    <time_frame>12 weeks</time_frame>
    <description>Toxicities will be evaluated on a weekly basis and will be classified according to their grade and relationship to study treatment. Chi-square testing will be employed to examine the difference in number of patients with grade 3 or greater non-hematologic toxicity between treatment and placebo groups.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Sickle Cell Disease</condition>
  <arm_group>
    <arm_group_label>Oral Decitabine and Tetrahydrouridine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral Decitabine and Tetrahydrouridine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oral Decitabine and Tetrahydrouridine</intervention_name>
    <description>Oral Decitabine and Oral Tetrahydrouridine (THU) given 1-2 hours apart on 2 consecutive days over 8 weeks</description>
    <arm_group_label>Oral Decitabine and Tetrahydrouridine</arm_group_label>
    <other_name>Dacogen, 5-aza-2'-deoxycytydine, THU</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Plain water will be dispensed at a similar volume and in the same containers as study drug. The water placebo has a similar appearance and taste to the study drug, since the study drug is highly diluted in water.</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Water</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 years or older.&#xD;
&#xD;
          -  Written, informed consent provided by the subject before study entry.&#xD;
&#xD;
          -  Confirmed Sickle Cell Disease (SCD) (SS, S-b0-thalassemia, S-b+-thalassemia or SC on&#xD;
             hemoglobin electrophoresis).&#xD;
&#xD;
          -  Symptomatic SCD while on 6 months of HU OR symptomatic SCD and intolerant of HU&#xD;
             (unable or unwilling to take HU due to hematological or other toxicities). Symptomatic&#xD;
             SCD is defined as having one of following:&#xD;
&#xD;
               -  Fetal Hemoglobin (HbF) &lt;5%, OR&#xD;
&#xD;
               -  3 or more pain episodes per year requiring parenteral narcotics, OR&#xD;
&#xD;
               -  1 or more acute chest syndrome episodes, OR&#xD;
&#xD;
               -  Hemoglobin &lt;9 g/dL and absolute reticulocyte count &lt;250,000/mm3.&#xD;
&#xD;
          -  Subject is in his/her steady state and not amidst any acute complication due to SCD&#xD;
             (i.e., hospitalization, acute pain, or acute chest syndrome in the past 14 days).&#xD;
&#xD;
          -  Regular compliance with comprehensive care and previous therapy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inability to give informed consent.&#xD;
&#xD;
          -  Experienced severe sepsis or septic shock within the previous 12 weeks.&#xD;
&#xD;
          -  Last HU dose was ingested within the previous 4 weeks.&#xD;
&#xD;
          -  Currently pregnant or breast-feeding.&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) greater than or equal to two times (2X) the upper limit&#xD;
             of normal or albumin &lt;2.0 mg/dL or direct (conjugated) bilirubin greater than or equal&#xD;
             to 1.5 mg/dl.&#xD;
&#xD;
          -  Serum creatinine &gt;2.9 mg/dL and calculated creatinine clearance &lt;30 mL/min.&#xD;
&#xD;
          -  Platelet count &gt;800 x 109/L.&#xD;
&#xD;
          -  Absolute neutrophil count &lt;1.5 x 109/L.&#xD;
&#xD;
          -  Female of active childbearing potential who is unwilling to use at least one of the&#xD;
             two following forms of birth control:&#xD;
&#xD;
             (i) not having heterosexual sexual contact beginning at the screening visit and&#xD;
             continuing until 4 weeks after the last dose of THU-decitabine OR (ii) intrauterine&#xD;
             device (IUD).&#xD;
&#xD;
          -  Sexually active male who is unwilling to use a condom when engaging in any sexual&#xD;
             contact with a female with child-bearing potential, beginning at the screening visit&#xD;
             and continuing until 4 weeks after taking the last dose of THU-decitabine. This&#xD;
             requirement applies also to males who have had a successful vasectomy.&#xD;
&#xD;
          -  Altered mental status or recurrent seizures requiring anti-seizure medications.&#xD;
&#xD;
          -  Moribund or any concurrent disease (e.g., hepatic, renal, cardiac, metabolic) of such&#xD;
             severity that death within 24 weeks is likely.&#xD;
&#xD;
          -  Concurrent diagnosis of malignancy including myelodysplastic syndromes (MDS),&#xD;
             leukemia, or an abnormal karyotype.&#xD;
&#xD;
          -  Vitamin-B12, folate, or iron deficient (until corrected).&#xD;
&#xD;
          -  New York Heart Association (NYHA) class III/IV status.&#xD;
&#xD;
          -  Eastern Co-operative Oncology Group (ECOG) performance status greater than or equal to&#xD;
             3.&#xD;
&#xD;
          -  Participant is on chronic transfusion therapy (e.g., for history of Transient Ischemic&#xD;
             Attack (TIA) or stroke) and medically contraindicated to discontinue transfusions&#xD;
             (unless multiple allo-antibodies prevent the patient from getting transfusions as&#xD;
             scheduled).&#xD;
&#xD;
          -  Known history of illicit drug or alcohol abuse within the past 12 months.&#xD;
&#xD;
          -  Other experimental or investigational drug therapy in the past 28 days.&#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>Yogen Saunthararajah, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Cleveland Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Illinois at Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2018</verification_date>
  <study_first_submitted>September 6, 2012</study_first_submitted>
  <study_first_submitted_qc>September 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 14, 2012</study_first_posted>
  <last_update_submitted>September 7, 2018</last_update_submitted>
  <last_update_submitted_qc>September 7, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">September 11, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>The Cleveland Clinic</investigator_affiliation>
    <investigator_full_name>Yogen Saunthararajah</investigator_full_name>
    <investigator_title>Staff in the Department of Hematology and Oncology</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anemia, Sickle Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Decitabine</mesh_term>
    <mesh_term>Tetrahydrouridine</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/NCT01685515
org study id: CASE 10Z11
nct id: NCT01685515
lead sponsor: 
collaborator: 
has dmc: Yes
The purposes of this study are to observe if oral tetrahydrouridine and decitabine can
      increase fetal hemoglobin levels and improve the symptoms of sickle cell disease, and to
      monitor how patient's bodies react to oral tetrahydrouridine and decitabine.
The purposes of this study are to observe if oral tetrahydrouridine and decitabine can
      increase fetal hemoglobin levels and improve the symptoms of sickle cell disease, and to
      monitor how patient's bodies react to oral tetrahydrouridine and decitabine. The overall
      purpose is to develop disease modifying treatment for sickle cell disease that is less
      cytotoxic than the current standard of care, and which can directly and more efficiently
      reactivate fetal hemoglobin levels. The hypothesis is that patients treated with oral
      tetrahydrouridine and decitabine will have the same chance of severe non-hematologic
      toxicities as the placebo group. The primary end-point is ≥ grade 3 non-hematologic toxicity.
      The investigators' hypothesis is that patients in the treatment groups receiving oral
      THU-decitabine 2X/week over 8 weeks (n=15) will be equivalent to placebo group (n=10) with
      regards to the chance of ≥ grade 3 non-hematologic toxicity.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Non-hematologic toxicity
time frame: 12 weeks
description: Toxicities will be evaluated on a weekly basis and will be classified according to their grade and relationship to study treatment. Chi-square testing will be employed to examine the difference in number of patients with grade 3 or greater non-hematologic toxicity between treatment and placebo groups.
arm group label: Oral Decitabine and Tetrahydrouridine
arm group type: Experimental
description: Oral Decitabine and Tetrahydrouridine
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo
intervention type: Drug
intervention name: Oral Decitabine and Tetrahydrouridine
description: Oral Decitabine and Oral Tetrahydrouridine (THU) given 1-2 hours apart on 2 consecutive days over 8 weeks
arm group label: Oral Decitabine and Tetrahydrouridine
other name: Dacogen, 5-aza-2'-deoxycytydine, THU
intervention type: Drug
intervention name: Placebo
description: Plain water will be dispensed at a similar volume and in the same containers as study drug. The water placebo has a similar appearance and taste to the study drug, since the study drug is highly diluted in water.
arm group label: Placebo
other name: Water
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Yogen Saunthararajah, MD
role: Principal Investigator
affiliation: The Cleveland Clinic
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: The Cleveland Clinic
investigator full name: Yogen Saunthararajah
investigator title: Staff in the Department of Hematology and Oncology
mesh term: Anemia, Sickle Cell
mesh term: Decitabine
mesh term: Tetrahydrouridine