<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/NCT03802695</url>
  </required_header>
  <id_info>
    <org_study_id>OGFT001-001</org_study_id>
    <nct_id>NCT03802695</nct_id>
  </id_info>
  <brief_title>A Phase 1 Study of Engineered Donor Grafts (Orca-Q) in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies</brief_title>
  <official_title>A Phase 1, Dose Escalation and Expansion Study of Engineered Donor Grafts Derived From Mobilized Peripheral Blood (Orca-Q, Formerly OrcaGraft), With Single Agent Graft Versus-host Disease Prophylaxis, in Recipients Undergoing Myeloablative Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Orca Biosystems, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Orca Biosystems, Inc.</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will evaluate the safety, tolerability, and efficacy of engineered donor grafts&#xD;
      (&quot;OrcaGraft&quot;/&quot;Orca-Q&quot;) in participants undergoing myeloablative allogeneic hematopoietic cell&#xD;
      transplant transplantation for hematologic malignancies.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 8, 2019</start_date>
  <completion_date type="Anticipated">April 1, 2026</completion_date>
  <primary_completion_date type="Anticipated">April 1, 2024</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Dose Limiting Toxicities</measure>
    <time_frame>28 Days after administration of Orca-Q/OrcaGraft</time_frame>
    <description>Safety and tolerability of Orca-Q (formerly OrcaGraft) in adults undergoing myeloablative allogeneic hematopoietic cell transplantation (MA-alloHCT) will be evaluated by identification of the following dose limiting toxicities: Grade ≥ 3 infusion-related reaction or cytokine release syndrome, Grade ≥ 3 acute GVHD, Any Grade ≥ 3 treatment-related non-hematologic event not clearly related to the underlying malignancy, intercurrent infection, the HCT conditioning regimen, or other pre-existing medical condition, and by instance of primary graft failure, defined as being alive without recovery of neutrophils during the evaluation period</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Primary Graft failure through Day +28 (dose expansion)</measure>
    <time_frame>28 Days after administration of Orca-Q/OrcaGraft</time_frame>
    <description>Primary graft failure in the dose expansion phase, defined as being alive without recovery of neutrophils during the evaluation period</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Neutrophil Engraftment through Day +28</measure>
    <time_frame>28 days after administration of Orca-Q/OrcaGraft</time_frame>
    <description>Neutrophil engraftment defined as an absolute neutrophil count of &gt;/=500/mm3 for 3 consecutive days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Platelet engraftment through Day +50</measure>
    <time_frame>50 days after administration of Orca-Q/OrcaGraft</time_frame>
    <description>Platelet engraftment is defined as achieving a platelet count &gt; 20,000/mm3 for 3 consecutive days without platelet transfusion in the preceding 7 days, by Day +50</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary graft failure through Day +100</measure>
    <time_frame>100 days after administration of Orca-Q/OrcaGraft</time_frame>
    <description>Secondary graft failure is defined as neutrophil engraftment followed by subsequent decline in absolute neutrophil counts &lt; 500 cells/μL, unresponsive to growth factor therapy, by Day +100</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment-emergent adverse events (TEAEs) through the safety reporting period</measure>
    <time_frame>100 days after administration of Orca-Q/OrcaGraft</time_frame>
    <description>TEAEs categorized by System Organ Lass and graded according to the CTCAE v5.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute GVHD through Day +100</measure>
    <time_frame>100 days after administration of Orca-Q/OrcaGraft</time_frame>
    <description>Acute GVHD will be staged and graded per Mount Sinai Acute GvHD International Consortium (MAGIC) Standardization criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Steroid-refractory acute GVHD through Day +100</measure>
    <time_frame>100 days after administration of Orca-Q/OrcaGraft</time_frame>
    <description>Steroid-refractory acute GVHD will be defined as per the EBMT-NIH-CIBMTR Task Force position statement</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Chronic GVHD through Day +365</measure>
    <time_frame>365 days after administration of Orca-Q/OrcaGraft</time_frame>
    <description>Chronic GVHD will be diagnosed per 2014 International NIH Chronic GVHD Diagnosis and Staging Consensus Working Group criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-Transplant Lymphoproliferative Disorder (PTLD) through Day +365</measure>
    <time_frame>365 days after administration of Orca-Q/OrcaGraft</time_frame>
    <description>PTLD is defined as a biopsy consistent with the 2017 World Health Organization (WHO) classification of PTLD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of non-relapse mortality (NRM) through Day +365</measure>
    <time_frame>365 days after administration of Orca-Q/OrcaGraft</time_frame>
    <description>NRM is defined as death without evidence of disease recurrence</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of disease relapse through Day +365</measure>
    <time_frame>365 days after administration of Orca-Q/OrcaGraft</time_frame>
    <description>Recurrence of primary disease for transplant</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>GVHD-free and relapse-free survival (GRFS) through Day +365</measure>
    <time_frame>365 days after administration of Orca-Q/OrcaGraft</time_frame>
    <description>Survival free from GVHD and relapse</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease-free survival (DFS) through Day +365</measure>
    <time_frame>365 days after administration of Orca-Q/OrcaGraft</time_frame>
    <description>Disease-free survival is the time from date of transplant to death or relapse, whichever comes first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival through Day +365</measure>
    <time_frame>365 days after administration of Orca-Q/OrcaGraft</time_frame>
    <description>OS is defined as the time from the date of transplant to the date of death from any cause or, for surviving patients, to the date of last follow-up.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">186</enrollment>
  <condition>Acute Myeloid Leukemia</condition>
  <condition>Acute Lymphoblastic Leukemia</condition>
  <condition>Myelodysplastic Syndromes</condition>
  <condition>Acute Leukemia</condition>
  <arm_group>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Recipients with HLA-identical or 1-allele mismatched (7/8 alleles) related or unrelated donor; with single-agent GVHD prophylaxis given</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Recipients with haploidentical-related donors; with single-agent GVHD prophylaxis given</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Recipients with an HLA-identical related or unrelated donor; no GVHD prophylaxis given</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>OrcaGraft (Orca-Q)</intervention_name>
    <description>engineered donor allograft</description>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_label>Arm B</arm_group_label>
    <arm_group_label>Arm C</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥ 18 and ≤ 65 years at the time of enrollment&#xD;
&#xD;
          2. Diagnosed acute myeloid, lymphoid or mixed phenotype leukemia, or high or very high&#xD;
             risk myelodysplasic syndrome (MDS) or Myelofibrosis&#xD;
&#xD;
          3. Planned to undergo myeloablative allogeneic hematopoietic stem cell transplant (HCT)&#xD;
&#xD;
          4. Matched to a 8/8 or 7/8 related or unrelated donor, or to a related haploidentical&#xD;
             donor&#xD;
&#xD;
          5. Estimated glomerular filtration rate (eGFR) &gt; 50 mL/minute&#xD;
&#xD;
          6. Cardiac ejection fraction at rest ≥ 45% or shortening fraction of ≥ 27% by&#xD;
             echocardiogram or radionuclide scan (MUGA)&#xD;
&#xD;
          7. Diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) ≥&#xD;
             50%&#xD;
&#xD;
          8. Total bilirubin &lt; 1.5 times upper limit of normal (ULN) (&lt; 3 times if attributed to&#xD;
             Gilbert's syndrome) and ALT/AST &lt; 3 times ULN&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          1. Prior allogeneic HCT&#xD;
&#xD;
          2. Currently receiving corticosteroids or other immunosuppressive therapy. Topical&#xD;
             corticosteroids or oral systemic corticosteroid doses less than or equal to 10 mg/day&#xD;
             are allowed.&#xD;
&#xD;
          3. Planned donor lymphocyte infusion (DLI)&#xD;
&#xD;
          4. Positive anti-donor HLA antibodies against a mismatched allele in the selected donor&#xD;
&#xD;
          5. Karnofsky performance score &lt; 70% (Appendix 12.7)&#xD;
&#xD;
          6. Hematopoietic cell transplantation-specific Comorbidity Index (HCT-CI) &gt; 4 (Appendix&#xD;
             12.8)&#xD;
&#xD;
          7. Uncontrolled bacterial, viral or fungal infections (currently taking antimicrobial&#xD;
             therapy and with progression or no clinical improvement) at time of enrollment&#xD;
&#xD;
          8. Seropositive for HIV-1 or -2, HTLV-1 or -2&#xD;
&#xD;
          9. Any uncontrolled autoimmune disease requiring active immunosuppressive treatment&#xD;
&#xD;
         10. Concurrent malignancies or active disease within 1 year, except non-melanoma skin&#xD;
             cancers that have been curatively resected&#xD;
&#xD;
         11. History of idiopathic or secondary myelofibrosis&#xD;
&#xD;
         12. Women who are pregnant or breastfeeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>James S McClellan, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Orca Biosystems, Inc.</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>James S McClellan, MD, PhD</last_name>
    <phone>1-530-414-9743</phone>
    <email>info@orcabiosystems.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>City of Hope</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Amandeep Salhotra, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>UC Davis</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mehrdad Abedi, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Stanford Health Care</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Robert Lowsky, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Emory University</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Edmund Waller, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>The University of Kansas Hospital</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joseph McGuirk, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ohio State University</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ayman Saad, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of Texas MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77054</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Samer Srour, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Froedtert Memorial Lutheran Hospital</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>January 10, 2019</study_first_submitted>
  <study_first_submitted_qc>January 10, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 14, 2019</study_first_posted>
  <last_update_submitted>March 21, 2023</last_update_submitted>
  <last_update_submitted_qc>March 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 23, 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>Leukemia</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Hematologic Neoplasms</mesh_term>
    <mesh_term>Myelodysplastic Syndromes</mesh_term>
  </condition_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/NCT03802695
org study id: OGFT001-001
nct id: NCT03802695
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This study will evaluate the safety, tolerability, and efficacy of engineered donor grafts
      ("OrcaGraft"/"Orca-Q") in participants undergoing myeloablative allogeneic hematopoietic cell
      transplant transplantation for hematologic malignancies.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Dose Limiting Toxicities
time frame: 28 Days after administration of Orca-Q/OrcaGraft
description: Safety and tolerability of Orca-Q (formerly OrcaGraft) in adults undergoing myeloablative allogeneic hematopoietic cell transplantation (MA-alloHCT) will be evaluated by identification of the following dose limiting toxicities: Grade ≥ 3 infusion-related reaction or cytokine release syndrome, Grade ≥ 3 acute GVHD, Any Grade ≥ 3 treatment-related non-hematologic event not clearly related to the underlying malignancy, intercurrent infection, the HCT conditioning regimen, or other pre-existing medical condition, and by instance of primary graft failure, defined as being alive without recovery of neutrophils during the evaluation period
measure: Primary Graft failure through Day +28 (dose expansion)
time frame: 28 Days after administration of Orca-Q/OrcaGraft
description: Primary graft failure in the dose expansion phase, defined as being alive without recovery of neutrophils during the evaluation period
measure: Neutrophil Engraftment through Day +28
time frame: 28 days after administration of Orca-Q/OrcaGraft
description: Neutrophil engraftment defined as an absolute neutrophil count of >/=500/mm3 for 3 consecutive days
measure: Platelet engraftment through Day +50
time frame: 50 days after administration of Orca-Q/OrcaGraft
description: Platelet engraftment is defined as achieving a platelet count > 20,000/mm3 for 3 consecutive days without platelet transfusion in the preceding 7 days, by Day +50
measure: Secondary graft failure through Day +100
time frame: 100 days after administration of Orca-Q/OrcaGraft
description: Secondary graft failure is defined as neutrophil engraftment followed by subsequent decline in absolute neutrophil counts < 500 cells/μL, unresponsive to growth factor therapy, by Day +100
measure: Treatment-emergent adverse events (TEAEs) through the safety reporting period
time frame: 100 days after administration of Orca-Q/OrcaGraft
description: TEAEs categorized by System Organ Lass and graded according to the CTCAE v5.0
measure: Acute GVHD through Day +100
time frame: 100 days after administration of Orca-Q/OrcaGraft
description: Acute GVHD will be staged and graded per Mount Sinai Acute GvHD International Consortium (MAGIC) Standardization criteria
measure: Steroid-refractory acute GVHD through Day +100
time frame: 100 days after administration of Orca-Q/OrcaGraft
description: Steroid-refractory acute GVHD will be defined as per the EBMT-NIH-CIBMTR Task Force position statement
measure: Chronic GVHD through Day +365
time frame: 365 days after administration of Orca-Q/OrcaGraft
description: Chronic GVHD will be diagnosed per 2014 International NIH Chronic GVHD Diagnosis and Staging Consensus Working Group criteria
measure: Post-Transplant Lymphoproliferative Disorder (PTLD) through Day +365
time frame: 365 days after administration of Orca-Q/OrcaGraft
description: PTLD is defined as a biopsy consistent with the 2017 World Health Organization (WHO) classification of PTLD
measure: Incidence of non-relapse mortality (NRM) through Day +365
time frame: 365 days after administration of Orca-Q/OrcaGraft
description: NRM is defined as death without evidence of disease recurrence
measure: Incidence of disease relapse through Day +365
time frame: 365 days after administration of Orca-Q/OrcaGraft
description: Recurrence of primary disease for transplant
measure: GVHD-free and relapse-free survival (GRFS) through Day +365
time frame: 365 days after administration of Orca-Q/OrcaGraft
description: Survival free from GVHD and relapse
measure: Disease-free survival (DFS) through Day +365
time frame: 365 days after administration of Orca-Q/OrcaGraft
description: Disease-free survival is the time from date of transplant to death or relapse, whichever comes first.
measure: Overall survival through Day +365
time frame: 365 days after administration of Orca-Q/OrcaGraft
description: OS is defined as the time from the date of transplant to the date of death from any cause or, for surviving patients, to the date of last follow-up.
arm group label: Arm A
arm group type: Experimental
description: Recipients with HLA-identical or 1-allele mismatched (7/8 alleles) related or unrelated donor; with single-agent GVHD prophylaxis given
arm group label: Arm B
arm group type: Experimental
description: Recipients with haploidentical-related donors; with single-agent GVHD prophylaxis given
arm group label: Arm C
arm group type: Experimental
description: Recipients with an HLA-identical related or unrelated donor; no GVHD prophylaxis given
intervention type: Biological
intervention name: OrcaGraft (Orca-Q)
description: engineered donor allograft
arm group label: Arm A
arm group label: Arm B
arm group label: Arm C
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: James S McClellan, MD, PhD
role: Study Director
affiliation: Orca Biosystems, Inc.
last name: James S McClellan, MD, PhD
phone: 1-530-414-9743
email: info@orcabiosystems.com
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Withdrawn
country: United States
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Hematologic Neoplasms
mesh term: Myelodysplastic Syndromes