<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/NCT04414046</url>
  </required_header>
  <id_info>
    <org_study_id>HAP-PID</org_study_id>
    <nct_id>NCT04414046</nct_id>
  </id_info>
  <brief_title>TCR Alpha Beta T-cell Depleted Haploidentical HCT in the Treatment of Primary Immunodeficiency and Inherited Metabolic Disorders in Children</brief_title>
  <official_title>Study of TCR Alpha Beta T-Cell and CD19 B-Cell Depletion for Hematopoietic Cell Transplantation From Haploidentical Donors in the Treatment of Primary Immunodeficiency and Inherited Metabolic Disorders in Children</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Johns Hopkins All Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Johns Hopkins All Children's Hospital</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 research is being done to learn if a new type of haploidentical transplantation using&#xD;
      TCR alpha beta and CD19 depleted stem cell graft from the donor is safe and effective to&#xD;
      treat the patient's underlying condition. This study will use stem cells obtained via&#xD;
      peripheral blood or bone marrow from parent or other half-matched family member donor. These&#xD;
      will be processed through a special device called CliniMACS, which is considered&#xD;
      investigational.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 22, 2020</start_date>
  <completion_date type="Anticipated">June 2024</completion_date>
  <primary_completion_date type="Anticipated">June 2024</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>Incidence of successful donor engraftment</measure>
    <time_frame>Day 100 after transplantation</time_frame>
    <description>The incidence of engraftment at day 100 will be described based on donor chimerism in the whole blood and or fractions sorted for T-cell and myeloid subsets. The donor chimerism will be scored as autologous reconstitution (&lt; 5% donor), mixed chimerism (5-49%=low mixed, 50-95%=high mixed), &gt; 95%=full donor chimerism.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival and Event-free survival</measure>
    <time_frame>Up to 2 years post transplant</time_frame>
    <description>Overall survival is defined as the time of enrollment to death from any cause or last follow up.&#xD;
Event-free survival is defined as the time of enrollment to death, primary or secondary graft failure, graft failure necessitating a second HCT procedure, DLI or stem cell boost given for treatment of falling chimerism, or disease recurrence</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kinetics of neutrophil engraftment</measure>
    <time_frame>Up to 42 days post transplant</time_frame>
    <description>Neutrophil engraftment defined as absolute neutrophil count ≥500/μL for 3 consecutive measurements on different days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kinetics of platelet engraftment</measure>
    <time_frame>Up to 42 days post transplant</time_frame>
    <description>Platelet engraftment defined as sustained platelet count &gt;20,000/μL and &gt;50,000//μL with no platelet transfusions in the preceding seven days.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Transplant-related mortality</measure>
    <time_frame>Up to 100 days post transplant</time_frame>
    <description>Rate of transplant-related mortality</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute grade II-IV GvHD</measure>
    <time_frame>Up to 2 years post transplant</time_frame>
    <description>Incidence and severity of acute graft versus host disease</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Chronic GvHD</measure>
    <time_frame>Up to 2 years post transplant</time_frame>
    <description>Incidence and severity of chronic graft versus host disease</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Primary graft failure</measure>
    <time_frame>Up to 2 years post transplant</time_frame>
    <description>Rates of primary graft failure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary graft failure</measure>
    <time_frame>Up to 2 years post transplant</time_frame>
    <description>Rates of secondary graft failure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Transplant-related complications</measure>
    <time_frame>Up to 2 years post transplant</time_frame>
    <description>Frequency of transplant-related complications following transplantation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Transplant-related infections</measure>
    <time_frame>Up to 2 years post transplant</time_frame>
    <description>Frequency of transplant-related infections following transplantation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cellular and Immunological reconstitution by laboratory evaluations</measure>
    <time_frame>Up to 2 years post transplant</time_frame>
    <description>The recovery of different lymphocyte subpopulation (CD3+; CD4+; CD8+; CD3+CD45RA+and CD45RO; TCR alpha beta; TCR gamma delta; CD19+)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">17</enrollment>
  <condition>Primary Immune Deficiency Disorders</condition>
  <condition>Metabolic Disease</condition>
  <arm_group>
    <arm_group_label>TCR alpha beta T cell depletion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The leukapheresis product will undergo TCR alpha beta negative selection following a standardized protocol</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Haploidentical Hematopoietic Cell Transplantation</intervention_name>
    <description>TCR alpha beta T-cell and CD19 B-cell depleted haploidentical transplantation</description>
    <arm_group_label>TCR alpha beta T cell depletion</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patient with any form of primary immune deficiency/dysregulatory disorders&#xD;
             characterized by aberrant immune function, abnormal hematopoiesis, systemic or organ&#xD;
             specific autoimmunity and/or non-malignant lymphoproliferation. This includes, but not&#xD;
             limited to:&#xD;
&#xD;
             I. Disorders of phagocytes: Chronic granulomatous disease, Leukocyte adhesion&#xD;
             deficiency, defects of IL-10 pathway, MonoMac syndrome&#xD;
&#xD;
             II. Defects of cellular and humoral immunity: Severe Combined Immunodeficiency&#xD;
             Disorder (infants with classic SCID up to 2 years of age will be excluded due to other&#xD;
             open protocol), X-linked hyper-IgM syndrome, DOCK8 deficiency, ZAP70 deficiency,&#xD;
             common variable immunodeficiency (CVID), Wiskott-Aldrich syndrome, NEMO deficiency.&#xD;
&#xD;
             III. Disorder of immune dysregulation: Immunodysregulation polyendocrinopathy&#xD;
             enteropathy X-linked (IPEX) syndrome, CTLA4 deficiency, LRBA deficiency, STAT1 GOF,&#xD;
             STAT3 GOF, X-linked lymphoproliferative disease etc.&#xD;
&#xD;
             IV. Other PIDs and immune dysregulatory disorders who can be benefitted by HCT as&#xD;
             deemed appropriate by the PI and the treating immunologist.&#xD;
&#xD;
          2. Histiocytic disorders including hemophagocytic lymphohistiocytosis (familial HLH&#xD;
             (types 1-5), secondary HLH (refractory to therapy or with recurrent episodes of hyper&#xD;
             inflammation) and multisystem refractory Langerhans cell histiocytosis.&#xD;
&#xD;
          3. Metabolic disorders that could improve or stabilize after stem cell transplantation&#xD;
             such as mucopolysaccharidoses, neurodegenerative disorders, osteopetrosis, etc.&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          1. Patient has a suitable genotypic identical match of 5/10. The donor and recipient must&#xD;
             be identical, as determined by high resolution typing, at least one allele of each of&#xD;
             the following genetic loci: HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1.&#xD;
&#xD;
          2. Patients must have adequate organ function measured by:&#xD;
&#xD;
               1. Cardiac: asymptomatic or if symptomatic then LVEF at rest must be ≥ 40% or SF ≥&#xD;
                  26%&#xD;
&#xD;
               2. Pulmonary: asymptomatic or if symptomatic DLCO ≥ 40% of predicted (corrected for&#xD;
                  hemoglobin) or pulse oximetry ≥ 92% on room air if the patient is unable to&#xD;
                  perform pulmonary function testing.&#xD;
&#xD;
               3. Renal: Creatinine clearance (CrCl) or glomerular filtration rate (GFR) must be &gt;&#xD;
                  50 mL/min/1.73 m2.&#xD;
&#xD;
               4. Hepatic: Serum conjugated (direct) bilirubin &lt; 2.0 x ULN for age; AST and ALT &lt;&#xD;
                  5.0 x ULN for age.&#xD;
&#xD;
               5. Karnofsky or Lansky (age-dependent) performance score ≥ 50&#xD;
&#xD;
          3. Signed written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Participants who have an HLA-matched sibling who is able and willing to donate bone&#xD;
             marrow. Patients with a HLA-matched unrelated donors are not excluded.&#xD;
&#xD;
          2. Pregnant or breastfeeding females.&#xD;
&#xD;
          3. Patient has HIV or uncontrolled fungal, bacterial or viral infections.&#xD;
&#xD;
          4. Patient has received prior solid organ transplant.&#xD;
&#xD;
          5. Patient has active GVHD (&gt; grade II) or chronic extensive GVHD due to a previous&#xD;
             allograft at the time of inclusion.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>21 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Deepak Chellapandian, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Johns Hopkins All Children's Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jade Hanson, MSN</last_name>
    <phone>7277676468</phone>
    <email>jade.hanson@jhmi.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Johns Hopkins All Children's Hospital</name>
      <address>
        <city>Saint Petersburg</city>
        <state>Florida</state>
        <zip>33701</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ian Snyder</last_name>
      <email>isnyder5@jhmi.edu</email>
    </contact>
    <investigator>
      <last_name>Deepak Chellapandian, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>May 24, 2020</study_first_submitted>
  <study_first_submitted_qc>May 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>September 8, 2023</last_update_submitted>
  <last_update_submitted_qc>September 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2023</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>Primary Immunodeficiency Diseases</mesh_term>
    <mesh_term>Metabolic Diseases</mesh_term>
    <mesh_term>Immunologic Deficiency Syndromes</mesh_term>
  </condition_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/NCT04414046
org study id: HAP-PID
nct id: NCT04414046
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This research is being done to learn if a new type of haploidentical transplantation using
      TCR alpha beta and CD19 depleted stem cell graft from the donor is safe and effective to
      treat the patient's underlying condition. This study will use stem cells obtained via
      peripheral blood or bone marrow from parent or other half-matched family member donor. These
      will be processed through a special device called CliniMACS, which is considered
      investigational.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of successful donor engraftment
time frame: Day 100 after transplantation
description: The incidence of engraftment at day 100 will be described based on donor chimerism in the whole blood and or fractions sorted for T-cell and myeloid subsets. The donor chimerism will be scored as autologous reconstitution (< 5% donor), mixed chimerism (5-49%=low mixed, 50-95%=high mixed), > 95%=full donor chimerism.
measure: Overall survival and Event-free survival
time frame: Up to 2 years post transplant
description: Overall survival is defined as the time of enrollment to death from any cause or last follow up.
Event-free survival is defined as the time of enrollment to death, primary or secondary graft failure, graft failure necessitating a second HCT procedure, DLI or stem cell boost given for treatment of falling chimerism, or disease recurrence
measure: Kinetics of neutrophil engraftment
time frame: Up to 42 days post transplant
description: Neutrophil engraftment defined as absolute neutrophil count ≥500/μL for 3 consecutive measurements on different days
measure: Kinetics of platelet engraftment
time frame: Up to 42 days post transplant
description: Platelet engraftment defined as sustained platelet count >20,000/μL and >50,000//μL with no platelet transfusions in the preceding seven days.
measure: Transplant-related mortality
time frame: Up to 100 days post transplant
description: Rate of transplant-related mortality
measure: Acute grade II-IV GvHD
time frame: Up to 2 years post transplant
description: Incidence and severity of acute graft versus host disease
measure: Chronic GvHD
time frame: Up to 2 years post transplant
description: Incidence and severity of chronic graft versus host disease
measure: Primary graft failure
time frame: Up to 2 years post transplant
description: Rates of primary graft failure
measure: Secondary graft failure
time frame: Up to 2 years post transplant
description: Rates of secondary graft failure
measure: Transplant-related complications
time frame: Up to 2 years post transplant
description: Frequency of transplant-related complications following transplantation
measure: Transplant-related infections
time frame: Up to 2 years post transplant
description: Frequency of transplant-related infections following transplantation
measure: Cellular and Immunological reconstitution by laboratory evaluations
time frame: Up to 2 years post transplant
description: The recovery of different lymphocyte subpopulation (CD3+; CD4+; CD8+; CD3+CD45RA+and CD45RO; TCR alpha beta; TCR gamma delta; CD19+)
arm group label: TCR alpha beta T cell depletion
arm group type: Experimental
description: The leukapheresis product will undergo TCR alpha beta negative selection following a standardized protocol
intervention type: Biological
intervention name: Haploidentical Hematopoietic Cell Transplantation
description: TCR alpha beta T-cell and CD19 B-cell depleted haploidentical transplantation
arm group label: TCR alpha beta T cell depletion
criteria: 
gender: All
minimum age: N/A
maximum age: 21 Years
healthy volunteers: No
last name: Deepak Chellapandian, MD
role: Principal Investigator
affiliation: Johns Hopkins All Children's Hospital
last name: Jade Hanson, MSN
phone: 7277676468
email: jade.hanson@jhmi.edu
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Primary Immunodeficiency Diseases
mesh term: Metabolic Diseases
mesh term: Immunologic Deficiency Syndromes
sharing ipd: No