<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/NCT03302754</url>
  </required_header>
  <id_info>
    <org_study_id>2017-2206</org_study_id>
    <nct_id>NCT03302754</nct_id>
  </id_info>
  <brief_title>Precision Dosing of Alemtuzumab</brief_title>
  <official_title>Precision Dosing of Alemtuzumab for Allogeneic Hematopoietic Cell Transplantation in Non-Malignant Diseases</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Children's Hospital Medical Center, Cincinnati</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Children's Hospital Medical Center, Cincinnati</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to conduct a pilot trial of a Precision Dosing approach to&#xD;
      alemtuzumab dosing for allogeneic hematopoietic cell transplantation of patients with&#xD;
      non-malignant diseases. The investigators will measure the ability to use a population PK&#xD;
      model of alemtuzumab to target patient Day 0 alemtuzumab levels to 0.15-0.6ug/mL in a pilot&#xD;
      study of 20 patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The hypothesis is that the model-informed dosing regimen will prospectively allow the&#xD;
      precision dosing of alemtuzumab to target Day 0 levels to fall between 0.15-0.6ug/mL in&#xD;
      greater than 80% of patients. The investigators have chosen a conservative pilot study&#xD;
      approach, and the aim is to achieve Day 0 alemtuzumab levels between 0.15-0.6ug/mL in greater&#xD;
      than 60% of 20 patients enrolled in this pilot study based on a Simon two-stage design as&#xD;
      detailed below.&#xD;
&#xD;
      A Simon two-stage design (Simon, 1989) is being used. The null hypothesis that 30% of&#xD;
      patients will achieve a Day 0 alemtuzumab level between 0.15-0.6ug/mL will be tested against&#xD;
      a one-sided alternative that the alemtuzumab dose modification will result in 60% of patients&#xD;
      achieving a Day 0 alemtuzumab level between 0.15-0.6ug/mL. In the first stage, 7 patients&#xD;
      will be accrued. If there are 2 or fewer patients that achieve Day 0 alemtuzumab levels&#xD;
      within the range of 0.15-0.6ug/mL, the study will be stopped. Otherwise, 13 additional&#xD;
      patients will be accrued for a total of 20. The null hypothesis will be rejected if 11 or&#xD;
      more patients achieve a Day 0 level of 0.15-0.6ug/mL within the total 20 patients. This&#xD;
      design yields a type I error rate of 0.04 and power of 0.82 when the true response rate is&#xD;
      0.60. The investigators will enroll up to 30 patients in order allow for subject withdrawal,&#xD;
      but will stop enrollment once 20 patients reach Day 0.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 5, 2017</start_date>
  <completion_date type="Actual">March 10, 2019</completion_date>
  <primary_completion_date type="Actual">March 10, 2019</primary_completion_date>
  <phase>N/A</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>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of patients who have alemtuzumab levels in the optimal therapeutic range on Day 0.</measure>
    <time_frame>100 Days</time_frame>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Allogeneic Hematopoietic Cell Transplantation</condition>
  <arm_group>
    <arm_group_label>Alemtuzumab</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Patients less than 15kg will be given 0.6mg/kg alemtuzumab divided over days -14, -13, and -12 (0.2mg/kg/dose).&#xD;
Patients greater than 15kg will be given a 3mg &quot;test&quot; dose on day -14 in order to limit the first dose to no more than 3 mg per the manufacturer's recommendation. This will be followed by 0.23mg/kg/dose on days -13 and -12 (to equal a total dose of approximately 0.5-0.6mg/kg).&#xD;
Alemtuzumab will be drawn into a sterile syringe and given to patients subcutaneously.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Alemtuzumab</intervention_name>
    <description>Alemtuzumab (Campath®) is a recombinant DNA-derived humanized monoclonal antibody directed against CD52. Alemtuzumab is produced in mammalian cell (Chinese hamster ovary) suspension culture in a medium containing neomycin. Neomycin is not detectable in the final product. Alemtuzumab is a sterile, clear, colorless, isotonic pH 6.8-7.4 solution for injection. Alemtuzumab is supplied in single-use clear glass ampules containing 30 mg of Alemtuzumab in 3 mL of solution. Single use vial of alemtuzumab contains 30 mg alemtuzumab, 8 mg sodium chloride, 1.44 mg dibasic sodium phosphate, 0.2 mg potassium chloride, 0.2 mg monobasic potassium phosphate, 0.1 mg polysorbate 80, and 0.0187 mg disodium edetate dihydrate.</description>
    <arm_group_label>Alemtuzumab</arm_group_label>
    <other_name>Campath</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients who are undergoing RIC HCT with alemtuzumab, fludarabine, and melphalan at&#xD;
             CCHMC for treatment of a non-malignant disease.&#xD;
&#xD;
          2. Age ≥ 6 weeks to ≤ 30 years (at time of enrollment).&#xD;
&#xD;
          3. For the first 7 patients, patients must have a 10/10 HLA matched related or unrelated&#xD;
             stem cell donor, or be receiving a CD34+ selected stem cell product. After the first 7&#xD;
             patients, any donor match may be allowed after data review by the PI and medical&#xD;
             monitor.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with a history of anaphylaxis to alemtuzumab.&#xD;
&#xD;
          2. Patients who have previously received alemtuzumab and have not cleared alemtuzumab&#xD;
             prior to the start of the preparative regimen.&#xD;
&#xD;
          3. Life expectancy less than 2 weeks.&#xD;
&#xD;
          4. Patients receiving dialysis.&#xD;
&#xD;
          5. Failure to sign informed consent and/or assent, or inability to undergo informed&#xD;
             consent process.&#xD;
&#xD;
          6. It is not medically advisable to obtain the specimens necessary for this study.&#xD;
&#xD;
          7. Not able to tolerate subcutaneous dosing (patients with severe skin conditions such as&#xD;
             epidermolysis bullosa).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Weeks</minimum_age>
    <maximum_age>30 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rebecca Marsh, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Hospital Medical Center, Cincinnati</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cincinnati Children's Hospital Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>September 18, 2017</study_first_submitted>
  <study_first_submitted_qc>October 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 5, 2017</study_first_posted>
  <last_update_submitted>October 3, 2019</last_update_submitted>
  <last_update_submitted_qc>October 3, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 4, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alemtuzumab</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/NCT03302754
org study id: 2017-2206
nct id: NCT03302754
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The purpose of this study is to conduct a pilot trial of a Precision Dosing approach to
      alemtuzumab dosing for allogeneic hematopoietic cell transplantation of patients with
      non-malignant diseases. The investigators will measure the ability to use a population PK
      model of alemtuzumab to target patient Day 0 alemtuzumab levels to 0.15-0.6ug/mL in a pilot
      study of 20 patients.
The hypothesis is that the model-informed dosing regimen will prospectively allow the
      precision dosing of alemtuzumab to target Day 0 levels to fall between 0.15-0.6ug/mL in
      greater than 80% of patients. The investigators have chosen a conservative pilot study
      approach, and the aim is to achieve Day 0 alemtuzumab levels between 0.15-0.6ug/mL in greater
      than 60% of 20 patients enrolled in this pilot study based on a Simon two-stage design as
      detailed below.

      A Simon two-stage design (Simon, 1989) is being used. The null hypothesis that 30% of
      patients will achieve a Day 0 alemtuzumab level between 0.15-0.6ug/mL will be tested against
      a one-sided alternative that the alemtuzumab dose modification will result in 60% of patients
      achieving a Day 0 alemtuzumab level between 0.15-0.6ug/mL. In the first stage, 7 patients
      will be accrued. If there are 2 or fewer patients that achieve Day 0 alemtuzumab levels
      within the range of 0.15-0.6ug/mL, the study will be stopped. Otherwise, 13 additional
      patients will be accrued for a total of 20. The null hypothesis will be rejected if 11 or
      more patients achieve a Day 0 level of 0.15-0.6ug/mL within the total 20 patients. This
      design yields a type I error rate of 0.04 and power of 0.82 when the true response rate is
      0.60. The investigators will enroll up to 30 patients in order allow for subject withdrawal,
      but will stop enrollment once 20 patients reach Day 0.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Percentage of patients who have alemtuzumab levels in the optimal therapeutic range on Day 0.
time frame: 100 Days
arm group label: Alemtuzumab
arm group type: Other
description: Patients less than 15kg will be given 0.6mg/kg alemtuzumab divided over days -14, -13, and -12 (0.2mg/kg/dose).
Patients greater than 15kg will be given a 3mg "test" dose on day -14 in order to limit the first dose to no more than 3 mg per the manufacturer's recommendation. This will be followed by 0.23mg/kg/dose on days -13 and -12 (to equal a total dose of approximately 0.5-0.6mg/kg).
Alemtuzumab will be drawn into a sterile syringe and given to patients subcutaneously.
intervention type: Drug
intervention name: Alemtuzumab
description: Alemtuzumab (Campath®) is a recombinant DNA-derived humanized monoclonal antibody directed against CD52. Alemtuzumab is produced in mammalian cell (Chinese hamster ovary) suspension culture in a medium containing neomycin. Neomycin is not detectable in the final product. Alemtuzumab is a sterile, clear, colorless, isotonic pH 6.8-7.4 solution for injection. Alemtuzumab is supplied in single-use clear glass ampules containing 30 mg of Alemtuzumab in 3 mL of solution. Single use vial of alemtuzumab contains 30 mg alemtuzumab, 8 mg sodium chloride, 1.44 mg dibasic sodium phosphate, 0.2 mg potassium chloride, 0.2 mg monobasic potassium phosphate, 0.1 mg polysorbate 80, and 0.0187 mg disodium edetate dihydrate.
arm group label: Alemtuzumab
other name: Campath
criteria: 
gender: All
minimum age: 6 Weeks
maximum age: 30 Years
healthy volunteers: No
last name: Rebecca Marsh, MD
role: Principal Investigator
affiliation: Children's Hospital Medical Center, Cincinnati
facility: 
country: United States
responsible party type: Sponsor
mesh term: Alemtuzumab
sharing ipd: No