xml: <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/NCT05968170</url>
    </required_header>
    <id_info>
      <org_study_id>CHLA-23-03064</org_study_id>
      <nct_id>NCT05968170</nct_id>
    </id_info>
    <brief_title>TCRαβ/CD19 Depletion of Stem Cell Grafts for Transplant</brief_title>
    <official_title>A Feasibility Study Using the CliniMACS Device for T-Cell Receptor (TCR) αβ+/CD19+ Depleted Hematopoietic Stem Cells for Patients Undergoing Transplant</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Neena Kapoor, M.D.</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Children's Hospital Los Angeles</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>Yes</is_fda_regulated_device>
      <is_unapproved_device>Yes</is_unapproved_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The CliniMACS® device is FDA-approved only for one indication (CD34+ selection). Additional&#xD;
        use of this device outside of this indication requires the use of feasibility studies.&#xD;
  &#xD;
        Children, adolescents and young adults with malignant and non-malignant conditions undergoing&#xD;
        hematopoietic stem cell transplants will have stem cells selected using alpha-beta+/CD19+&#xD;
        cell depletion. This is a single arm feasibility study using this processing of peripheral&#xD;
        stem cells with alternative donor sources (haploidentical, mismatched, matched unrelated) to&#xD;
        determine efficacy as seen by engraftment and graft-versus-host disease (GVHD).&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Hematopoietic stem cell transplantation (HSCT) is recognized as an effective cure for a wide&#xD;
        range of diagnoses including hematologic malignancies, bone marrow failure syndromes, red&#xD;
        blood cell disorders (sickle cell, beta thalassemia), white blood cell disorders (CGD), and&#xD;
        immune deficiency disorders. Current therapy with allogeneic HCT from HLA-matched sibling&#xD;
        donors has shown to be a potentially curative option for children with high-risk and/or&#xD;
        relapsed hematologic malignancies (ALL/AML) as well as primary immune deficiency disorders&#xD;
        (PID), however only 25-30% of patients have an HLA-identical matched sibling. Alternative&#xD;
        stem cell sources include matched unrelated donors (MUD) and unrelated cord blood (UCB),&#xD;
        however, the likelihood of finding an unrelated match can range between 29-79% depending on&#xD;
        the patient's ethnic background. Since 2015, the CHLA Transplant and Cellular Therapy Program&#xD;
        has performed approximately 90 ex vivo processed haploidentical transplants. Greater than 80%&#xD;
        of our patients belong to racial/ethnic groups with limited unrelated donor availability,&#xD;
        relying heavily on haploidentical donors. This lack of matched stem cells represents a&#xD;
        significant access disparity for underrepresented minorities with life-threatening&#xD;
        hematologic or immunologic conditions to undergo a potentially curative HSCT.&#xD;
  &#xD;
        The FDA approved the use of the CliniMACS CD34+ Reagent System as a Humanitarian Use Device&#xD;
        for the prevention of GVHD in patients with acute myeloid leukemia (AML) in first complete&#xD;
        remission undergoing allogeneic hematopoietic stem cell transplantation (HSCT) from a matched&#xD;
        related donor. The CliniMACS CD34+ Reagent System decreases the risk of developing GVHD by&#xD;
        efficiently removing donor T-cells from the graft prior to infusion by enriching CD34+ blood&#xD;
        stem cells, which help to repopulate the patient's immune system. FDA approval was based on&#xD;
        data from a phase II, single-arm, multi-center study conducted by the Blood and Marrow&#xD;
        Transplant Clinical Trials Network that showed after an intensive myeloablative conditioning,&#xD;
        receiving a stem cell transplant from a matched related donor processed through the CliniMACS&#xD;
        CD34+ Reagent System as a GVHD prophylaxis led to a low incidence of chronic GVHD, about 19%&#xD;
        at 2 years post-transplant. However, removal of all cells except CD34+ selected complicates&#xD;
        immune recovery (delay in CD4+ cells) leading to higher rates of opportunistic viral&#xD;
        infections and transplant-related mortality.&#xD;
  &#xD;
        The use of CD34+ selected processing has facilitated approximately 42 HSCTs in combination of&#xD;
        TCRαβ+/CD19 depletion at CHLA. The new approach to ex vivo processing utilizes negative&#xD;
        depletion of cells thought to be responsible for the development of aGVHD, αβ TCR positive&#xD;
        T-cells and includes simultaneous depletion of CD19+ B-cells. Since 2015, CHLA has conducted&#xD;
        TCRαβ/CD19+ depleted HSCTs successfully on several protocols, including the ONC1401 KIR Study&#xD;
        (IDE#16412).&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 1, 2023</start_date>
    <completion_date type="Anticipated">July 1, 2035</completion_date>
    <primary_completion_date type="Anticipated">July 1, 2028</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>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Incidence of grade 3-4 acute and/or chronic GVHD at Day+100</measure>
      <time_frame>Day+100 post-HSCT</time_frame>
      <description>Assess the cumulative incidence of severe GVHD following HSCT with TCRαβ+/CD19+ T-cell depleted grafts, as determined by the presence of Grade III-IV aGVHD and/or cGVHD by Day+100 post-HSCT.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Incidence of engraftment at Day+30.</measure>
      <time_frame>Day+30 post-HSCT</time_frame>
      <description>Assess the efficacy of TCRαβ+/CD19+ T-cell depleted HSCTs as measured by the engraftment of donor cells by Day+30 post-HSCT.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of transplant-related mortality at 1-year post-HSCT.</measure>
      <time_frame>1-Year post-HSCT</time_frame>
      <description>Assess the efficacy of TCRαβ+/CD19+ T-cell depleted HSCTs as measured by the incidence of transplant-related mortality at 1-year post-HSCT.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of T-cell reconstitution at Day+180 (CD4+ T-cell count &gt; 200 and proliferation to PHA &gt; 50% control).</measure>
      <time_frame>Day+180 post-HSCT</time_frame>
      <description>Assess the immune reconstitution following TCRαβ+/CD19+ T-cell depleted HSCTs as measured by the presence of expanded T-cell numbers and function at Day+180 post-HSCT(CD4+ T-cell count &gt; 200 and proliferation to PHA &gt; 50% control).</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Incidence of microbial contamination of the infused cells product leading to possible infection in the recipient (i.e., antibiotics needed for &gt; 48 hours).</measure>
      <time_frame>Day+30</time_frame>
      <description>Assess the risk of microbial contamination in TCRαβ+/CD19+ T-cell depleted products from the CliniMACS® device.</description>
    </other_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">45</enrollment>
    <condition>Graft Vs Host Disease</condition>
    <condition>Graft-versus-host-disease</condition>
    <condition>Acute Myeloid Leukemia</condition>
    <condition>Acute Lymphoblastic Leukemia</condition>
    <condition>Non-hematologic Malignancy</condition>
    <condition>Hematologic Malignancy</condition>
    <arm_group>
      <arm_group_label>Patients receiving allogeneic hematopoietic stem cell transplants</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The test product is an αβ+/CD19+ T-cell depleted stem cell product using the CliniMACS system. The test product is given intravenously over a period of time as dictated by the final volume of the infused product (5mL/kg/hour).&#xD;
  The target dose of CD34+ cells is 20-40 x 10^6/kg, but a minimum of 5 x 10^6/kg is required. The target dose of TCRαβ+ T-cells and CD19+/CD20+ T-cells is ≤ 1 x 10^5/kg.</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>CliniMACS® device</intervention_name>
      <description>CliniMACS TCR αβ+/CD19+ cell depletion for related or unrelated haploidentical/mismatched/matched hematopoietic stem cell transplant patients and/or high risk GVHD patients.</description>
      <arm_group_label>Patients receiving allogeneic hematopoietic stem cell transplants</arm_group_label>
      <other_name>CliniMACS® CD19 reagent system</other_name>
      <other_name>CliniMACS® depletion tubing set</other_name>
      <other_name>CliniMACS® TCR α/β reagent system</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Written informed consent (and written assent, if applicable) obtained prior to&#xD;
               enrollment.&#xD;
  &#xD;
            -  Age &lt; 21.&#xD;
  &#xD;
            -  Lansky Play-Performance Scale or Karnofsky Index score ≥ 60%.&#xD;
  &#xD;
            -  Adequate organ function (within 4 weeks of initiation of preparative regimen) as&#xD;
               evaluated per institutional guidelines. Adequate major organ system function as&#xD;
               demonstrated by:&#xD;
  &#xD;
                 -  Renal: Creatinine clearance or GFR of ≥ 60mL/min/1.73m2.&#xD;
  &#xD;
                 -  Hepatic: total bilirubin &lt; 2 mg/dL (unless due to Gilbert syndrome) and ALT/AST ≤&#xD;
                    2.5 times the upper limit of normal.&#xD;
  &#xD;
                 -  Cardiac: LVEF at rest ≥ 50% or SF ≥ 27% (by MUGA or ECHO).&#xD;
  &#xD;
                 -  Pulmonary: DLCO, FEV1, and FVC ≥ 50% of predicted corrected for hemoglobin. For&#xD;
                    patients &lt; 7 years of age or those unable to perform PFTs: O2 Sat ˃ 92% on room&#xD;
                    air by pulse oximetry and on no supplemental O2 at rest.&#xD;
  &#xD;
            -  Available donor (matched/mismatched unrelated, mismatched related, related&#xD;
               haploidentical) who is healthy and willing to donate peripheral blood stem cells.&#xD;
  &#xD;
            -  Patients that have been diagnosed with graft rejection/failure or relapse may be&#xD;
               eligible to receive a second transplant pending patient status.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patients with HIV or uncontrolled fungal, bacterial, or viral infections.&#xD;
  &#xD;
            -  Patients with active CNS leukemia or any other active site of extramedullary disease&#xD;
               at the time of enrollment.&#xD;
  &#xD;
            -  Recipient with HLA antibody against donor.&#xD;
  &#xD;
            -  Patients that are pregnant, breastfeeding or unwilling to practice birth control&#xD;
               during participation of the study.&#xD;
  &#xD;
            -  Any condition that, in the opinion of the Sponsor-Investigator, would compromise the&#xD;
               safety of the participant, prevent study participation, or interfere with the&#xD;
               evaluation of study endpoints.&#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>Neena Kapoor, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Children's Hospital Los Angeles</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Elizabeth Kissell, MS</last_name>
      <phone>323-361-5286</phone>
      <email>ekissell@chla.usc.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Neena Kapoor, MD</last_name>
      <phone>323-361-2434</phone>
      <email>nkapoor@chla.usc.edu</email>
    </overall_contact_backup>
    <reference>
      <citation>Oliansky DM, Rizzo JD, Aplan PD, Arceci RJ, Leone L, Ravindranath Y, Sanders JE, Smith FO 3rd, Wilmot F, McCarthy PL Jr, Hahn T. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of acute myeloid leukemia in children: an evidence-based review. Biol Blood Marrow Transplant. 2007 Jan;13(1):1-25. doi: 10.1016/j.bbmt.2006.10.024.</citation>
      <PMID>17222748</PMID>
    </reference>
    <reference>
      <citation>Oliansky DM, Camitta B, Gaynon P, Nieder ML, Parsons SK, Pulsipher MA, Dillon H, Ratko TA, Wall D, McCarthy PL Jr, Hahn T; American Society for Blood and Marrow Transplantation. Role of cytotoxic therapy with hematopoietic stem cell transplantation in the treatment of pediatric acute lymphoblastic leukemia: update of the 2005 evidence-based review. Biol Blood Marrow Transplant. 2012 Apr;18(4):505-22. doi: 10.1016/j.bbmt.2011.12.585. Epub 2011 Dec 29. Erratum In: Biol Blood Marrow Transplant. 2012 Sep;18(9):1466.</citation>
      <PMID>22209888</PMID>
    </reference>
    <reference>
      <citation>Leung W, Campana D, Yang J, Pei D, Coustan-Smith E, Gan K, Rubnitz JE, Sandlund JT, Ribeiro RC, Srinivasan A, Hartford C, Triplett BM, Dallas M, Pillai A, Handgretinger R, Laver JH, Pui CH. High success rate of hematopoietic cell transplantation regardless of donor source in children with very high-risk leukemia. Blood. 2011 Jul 14;118(2):223-30. doi: 10.1182/blood-2011-01-333070. Epub 2011 May 25.</citation>
      <PMID>21613256</PMID>
    </reference>
    <reference>
      <citation>Fuchs EJ. Haploidentical transplantation for hematologic malignancies: where do we stand? Hematology Am Soc Hematol Educ Program. 2012;2012:230-6. doi: 10.1182/asheducation-2012.1.230.</citation>
      <PMID>23233586</PMID>
    </reference>
    <reference>
      <citation>Zeidan AM, Forde PM, Symons H, Chen A, Smith BD, Pratz K, Carraway H, Gladstone DE, Fuchs EJ, Luznik L, Jones RJ, Bolanos-Meade J. HLA-haploidentical donor lymphocyte infusions for patients with relapsed hematologic malignancies after related HLA-haploidentical bone marrow transplantation. Biol Blood Marrow Transplant. 2014 Mar;20(3):314-8. doi: 10.1016/j.bbmt.2013.11.020. Epub 2013 Dec 1.</citation>
      <PMID>24296490</PMID>
    </reference>
    <reference>
      <citation>Food and Drug Administration, HHS. Eligibility determination for donors of human cells, tissues, and cellular and tissue-based products. Final rule. Fed Regist. 2004 May 25;69(101):29785-834.</citation>
      <PMID>15160713</PMID>
    </reference>
    <reference>
      <citation>Food and Drug Administration, HHS. Current good tissue practice for human cell, tissue, and cellular and tissue-based product establishments; inspection and enforcement. Final rule. Fed Regist. 2004 Nov 24;69(226):68611-88.</citation>
      <PMID>15562555</PMID>
    </reference>
    <reference>
      <citation>Abdelhakim H, Abdel-Azim H, Saad A. Role of alphabeta T Cell Depletion in Prevention of Graft versus Host Disease. Biomedicines. 2017 Jun 26;5(3):35. doi: 10.3390/biomedicines5030035.</citation>
      <PMID>28672883</PMID>
    </reference>
    <reference>
      <citation>Radestad E, Sundin M, Torlen J, Thunberg S, Onfelt B, Ljungman P, Watz E, Mattsson J, Uhlin M. Individualization of Hematopoietic Stem Cell Transplantation Using Alpha/Beta T-Cell Depletion. Front Immunol. 2019 Feb 11;10:189. doi: 10.3389/fimmu.2019.00189. eCollection 2019.</citation>
      <PMID>30804948</PMID>
    </reference>
    <reference>
      <citation>Ciurea SO, Bayraktar UD. &quot;No donor&quot;? Consider a haploidentical transplant. Blood Rev. 2015 Mar;29(2):63-70. doi: 10.1016/j.blre.2014.09.009. Epub 2014 Sep 30.</citation>
      <PMID>25307958</PMID>
    </reference>
    <reference>
      <citation>Gournay V, Dumas G, Lavillegrand JR, Hariri G, Urbina T, Baudel JL, Ait-Oufella H, Maury E, Brissot E, Legrand O, Malard F, Mohty M, Guidet B, Dulery R, Bige N. Outcome of allogeneic hematopoietic stem cell transplant recipients admitted to the intensive care unit with a focus on haploidentical graft and sequential conditioning regimen: results of a retrospective study. Ann Hematol. 2021 Nov;100(11):2787-2797. doi: 10.1007/s00277-021-04640-7. Epub 2021 Sep 3.</citation>
      <PMID>34476574</PMID>
    </reference>
    <reference>
      <citation>Giardino S, Bagnasco F, Falco M, Miano M, Pierri F, Risso M, Terranova P, Di Martino D, Massaccesi E, Ricci M, Chianucci B, Dell'Orso G, Sabatini F, Podesta M, Lanino E, Faraci M. Haploidentical Stem Cell Transplantation After TCR-alphabeta+ and CD19+ Cells Depletion In Children With Congenital Non-Malignant Disease. Transplant Cell Ther. 2022 Jul;28(7):394.e1-394.e9. doi: 10.1016/j.jtct.2022.04.002. Epub 2022 Apr 8.</citation>
      <PMID>35405368</PMID>
    </reference>
    <reference>
      <citation>Arnold DE, MacMath D, Seif AE, Heimall JR, Wang Y, Monos D, Grupp SA, Bunin NJ. Immune Reconstitution Following TCRalphabeta/CD19-Depleted Hematopoietic Cell Transplantation for Hematologic Malignancy in Pediatric Patients. Transplant Cell Ther. 2021 Feb;27(2):169.e1-169.e9. doi: 10.1016/j.jtct.2020.10.006. Epub 2020 Dec 10.</citation>
      <PMID>33830028</PMID>
    </reference>
    <reference>
      <citation>Mitchell R, Cole T, Shaw PJ, Mechinaud F, O'Brien T, Fraser C. TCR alpha+ beta+ /CD19+ cell-depleted hematopoietic stem cell transplantation for pediatric patients. Pediatr Transplant. 2019 Sep;23(6):e13517. doi: 10.1111/petr.13517. Epub 2019 Jul 4.</citation>
      <PMID>31271477</PMID>
    </reference>
    <reference>
      <citation>Bethge WA, Eyrich M, Mielke S, Meisel R, Niederwieser D, Schlegel PG, Schulz A, Greil J, Bunjes D, Brecht A, Kuball J, Schumm M, Vucinic V, Wiesneth M, Bonig H, Westinga K, Biedermann S, Holtkamp S, Karitzky S, Malchow M, Siewert C, Handgretinger R, Lang P. Results of a multicenter phase I/II trial of TCRalphabeta and CD19-depleted haploidentical hematopoietic stem cell transplantation for adult and pediatric patients. Bone Marrow Transplant. 2022 Mar;57(3):423-430. doi: 10.1038/s41409-021-01551-z. Epub 2021 Dec 24.</citation>
      <PMID>34952929</PMID>
    </reference>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>April 18, 2022</study_first_submitted>
    <study_first_submitted_qc>July 20, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 1, 2023</study_first_posted>
    <last_update_submitted>July 20, 2023</last_update_submitted>
    <last_update_submitted_qc>July 20, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>Children's Hospital Los Angeles</investigator_affiliation>
      <investigator_full_name>Neena Kapoor, M.D.</investigator_full_name>
      <investigator_title>Sponsor-Investigator</investigator_title>
    </responsible_party>
    <keyword>Reduce Graft Vs Host Disease</keyword>
    <keyword>Transplant</keyword>
    <keyword>Depletion of Stem Cell Grafts</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Leukemia</mesh_term>
      <mesh_term>Neoplasms</mesh_term>
      <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
      <mesh_term>Hematologic Neoplasms</mesh_term>
      <mesh_term>Graft vs Host Disease</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>The data will be made available internally to other sub-investigators that have expressed interest. Data that will be shared must go through the Sponsor-Investigator and will be redacted (if not already done) prior to receiving the data so that no identifying information is present.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
      <ipd_time_frame>Data will be made available upon request by submitting criteria of interest. The Sponsor-Investigator will provide a copy of the data. The copy will be indefinitely available to the interested party.</ipd_time_frame>
      <ipd_access_criteria>Data will be made available upon request by submitting criteria of interest. A copy of the redacted data will be given. No other party will have access to the database at any time outside of the Sponsor-Investigator and data management/CRC team.</ipd_access_criteria>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05968170
  org study id: CHLA-23-03064
  nct id: NCT05968170
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: Yes
  is unapproved device: Yes
  The CliniMACS® device is FDA-approved only for one indication (CD34+ selection). Additional
        use of this device outside of this indication requires the use of feasibility studies.
  
        Children, adolescents and young adults with malignant and non-malignant conditions undergoing
        hematopoietic stem cell transplants will have stem cells selected using alpha-beta+/CD19+
        cell depletion. This is a single arm feasibility study using this processing of peripheral
        stem cells with alternative donor sources (haploidentical, mismatched, matched unrelated) to
        determine efficacy as seen by engraftment and graft-versus-host disease (GVHD).
  Hematopoietic stem cell transplantation (HSCT) is recognized as an effective cure for a wide
        range of diagnoses including hematologic malignancies, bone marrow failure syndromes, red
        blood cell disorders (sickle cell, beta thalassemia), white blood cell disorders (CGD), and
        immune deficiency disorders. Current therapy with allogeneic HCT from HLA-matched sibling
        donors has shown to be a potentially curative option for children with high-risk and/or
        relapsed hematologic malignancies (ALL/AML) as well as primary immune deficiency disorders
        (PID), however only 25-30% of patients have an HLA-identical matched sibling. Alternative
        stem cell sources include matched unrelated donors (MUD) and unrelated cord blood (UCB),
        however, the likelihood of finding an unrelated match can range between 29-79% depending on
        the patient's ethnic background. Since 2015, the CHLA Transplant and Cellular Therapy Program
        has performed approximately 90 ex vivo processed haploidentical transplants. Greater than 80%
        of our patients belong to racial/ethnic groups with limited unrelated donor availability,
        relying heavily on haploidentical donors. This lack of matched stem cells represents a
        significant access disparity for underrepresented minorities with life-threatening
        hematologic or immunologic conditions to undergo a potentially curative HSCT.
  
        The FDA approved the use of the CliniMACS CD34+ Reagent System as a Humanitarian Use Device
        for the prevention of GVHD in patients with acute myeloid leukemia (AML) in first complete
        remission undergoing allogeneic hematopoietic stem cell transplantation (HSCT) from a matched
        related donor. The CliniMACS CD34+ Reagent System decreases the risk of developing GVHD by
        efficiently removing donor T-cells from the graft prior to infusion by enriching CD34+ blood
        stem cells, which help to repopulate the patient's immune system. FDA approval was based on
        data from a phase II, single-arm, multi-center study conducted by the Blood and Marrow
        Transplant Clinical Trials Network that showed after an intensive myeloablative conditioning,
        receiving a stem cell transplant from a matched related donor processed through the CliniMACS
        CD34+ Reagent System as a GVHD prophylaxis led to a low incidence of chronic GVHD, about 19%
        at 2 years post-transplant. However, removal of all cells except CD34+ selected complicates
        immune recovery (delay in CD4+ cells) leading to higher rates of opportunistic viral
        infections and transplant-related mortality.
  
        The use of CD34+ selected processing has facilitated approximately 42 HSCTs in combination of
        TCRαβ+/CD19 depletion at CHLA. The new approach to ex vivo processing utilizes negative
        depletion of cells thought to be responsible for the development of aGVHD, αβ TCR positive
        T-cells and includes simultaneous depletion of CD19+ B-cells. Since 2015, CHLA has conducted
        TCRαβ/CD19+ depleted HSCTs successfully on several protocols, including the ONC1401 KIR Study
        (IDE#16412).
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Incidence of grade 3-4 acute and/or chronic GVHD at Day+100
  time frame: Day+100 post-HSCT
  description: Assess the cumulative incidence of severe GVHD following HSCT with TCRαβ+/CD19+ T-cell depleted grafts, as determined by the presence of Grade III-IV aGVHD and/or cGVHD by Day+100 post-HSCT.
  measure: Incidence of engraftment at Day+30.
  time frame: Day+30 post-HSCT
  description: Assess the efficacy of TCRαβ+/CD19+ T-cell depleted HSCTs as measured by the engraftment of donor cells by Day+30 post-HSCT.
  measure: Incidence of transplant-related mortality at 1-year post-HSCT.
  time frame: 1-Year post-HSCT
  description: Assess the efficacy of TCRαβ+/CD19+ T-cell depleted HSCTs as measured by the incidence of transplant-related mortality at 1-year post-HSCT.
  measure: Incidence of T-cell reconstitution at Day+180 (CD4+ T-cell count > 200 and proliferation to PHA > 50% control).
  time frame: Day+180 post-HSCT
  description: Assess the immune reconstitution following TCRαβ+/CD19+ T-cell depleted HSCTs as measured by the presence of expanded T-cell numbers and function at Day+180 post-HSCT(CD4+ T-cell count > 200 and proliferation to PHA > 50% control).
  measure: Incidence of microbial contamination of the infused cells product leading to possible infection in the recipient (i.e., antibiotics needed for > 48 hours).
  time frame: Day+30
  description: Assess the risk of microbial contamination in TCRαβ+/CD19+ T-cell depleted products from the CliniMACS® device.
  arm group label: Patients receiving allogeneic hematopoietic stem cell transplants
  arm group type: Experimental
  description: The test product is an αβ+/CD19+ T-cell depleted stem cell product using the CliniMACS system. The test product is given intravenously over a period of time as dictated by the final volume of the infused product (5mL/kg/hour).
  The target dose of CD34+ cells is 20-40 x 10^6/kg, but a minimum of 5 x 10^6/kg is required. The target dose of TCRαβ+ T-cells and CD19+/CD20+ T-cells is ≤ 1 x 10^5/kg.
  intervention type: Device
  intervention name: CliniMACS® device
  description: CliniMACS TCR αβ+/CD19+ cell depletion for related or unrelated haploidentical/mismatched/matched hematopoietic stem cell transplant patients and/or high risk GVHD patients.
  arm group label: Patients receiving allogeneic hematopoietic stem cell transplants
  other name: CliniMACS® CD19 reagent system
  other name: CliniMACS® depletion tubing set
  other name: CliniMACS® TCR α/β reagent system
  criteria: 
  gender: All
  minimum age: N/A
  maximum age: 21 Years
  healthy volunteers: No
  last name: Neena Kapoor, MD
  role: Principal Investigator
  affiliation: Children's Hospital Los Angeles
  last name: Elizabeth Kissell, MS
  phone: 323-361-5286
  email: ekissell@chla.usc.edu
  last name: Neena Kapoor, MD
  phone: 323-361-2434
  email: nkapoor@chla.usc.edu
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  PMID: 17222748
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  PMID: 34952929
  responsible party type: Sponsor-Investigator
  investigator affiliation: Children's Hospital Los Angeles
  investigator full name: Neena Kapoor, M.D.
  investigator title: Sponsor-Investigator
  mesh term: Leukemia
  mesh term: Neoplasms
  mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
  mesh term: Hematologic Neoplasms
  mesh term: Graft vs Host Disease
  sharing ipd: Yes
  ipd description: The data will be made available internally to other sub-investigators that have expressed interest. Data that will be shared must go through the Sponsor-Investigator and will be redacted (if not already done) prior to receiving the data so that no identifying information is present.
  ipd info type: Study Protocol
  ipd info type: Informed Consent Form (ICF)
  ipd time frame: Data will be made available upon request by submitting criteria of interest. The Sponsor-Investigator will provide a copy of the data. The copy will be indefinitely available to the interested party.
  ipd access criteria: Data will be made available upon request by submitting criteria of interest. A copy of the redacted data will be given. No other party will have access to the database at any time outside of the Sponsor-Investigator and data management/CRC team.