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/NCT05984199</url>
    </required_header>
    <id_info>
      <org_study_id>VBP301</org_study_id>
      <nct_id>NCT05984199</nct_id>
    </id_info>
    <brief_title>Donor-Derived Anti-CD33 CAR T Cell Therapy (VCAR33) in Patients With Relapsed or Refractory AML After Allogeneic Hematopoietic Cell Transplant</brief_title>
    <official_title>Phase 1/2 Study of Donor-Derived Anti-CD33 Chimeric Antigen Receptor Expressing T Cells (VCAR33) in Patients With Relapsed or Refractory Acute Myeloid Leukemia After Allogeneic Hematopoietic Cell Transplantation</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Vor Biopharma</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Vor Biopharma</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 is a Phase 1/2, multicenter, open-label, first-in-human (FIH) study of donor-derived&#xD;
        anti-CD33 Chimeric Antigen Receptor (CAR) T cell therapy (VCAR33) in patients with relapsed&#xD;
        or refractory Acute Myeloid Leukemia (AML) after human leukocyte antigen (HLA)-matched&#xD;
        allogeneic hematopoietic cell transplant (alloHCT).&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        CD33 is a preferential target for AML CAR T cell therapy due to its surface expression on the&#xD;
        majority (&gt;80%) of AML blasts and due to the extensive prior clinical experience&#xD;
        demonstrating safety and efficacy of targeting CD33 with Mylotarg (gemtuzumab ozogamicin).&#xD;
        VCAR33 is being developed as a potential new treatment for patients with relapsed/refractory&#xD;
        (R/R) AML after alloHCT. In this Phase 1/2 trial, the safety and efficacy of&#xD;
        lentiviral-transduced CD33-directed CAR T cells (VCAR33) generated from the patient's prior&#xD;
        allogeneic stem cell donor will be tested. It is hypothesized that CAR T cell production from&#xD;
        healthy donors will not only eliminate delays in production due to lymphopenia but also&#xD;
        reduce concerns for suboptimal T cell function from exposure to systemic immunosuppression or&#xD;
        chemotherapeutic agents. Approximately 24 eligible patients with R/R AML after alloHCT will&#xD;
        be enrolled in one of two separate arms based on disease burden (morphologic disease versus&#xD;
        measurable residual disease (MRD ) positive). The maximum tolerated dose of VCAR33 will be&#xD;
        determined using a 3+3 trial design within each arm. Dose escalation can only occur after a&#xD;
        minimum of 3 patients have completed the dose-limiting toxicity (DLT) observation period.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">November 2026</completion_date>
    <primary_completion_date type="Anticipated">December 2024</primary_completion_date>
    <phase>Phase 1/Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Incidence of dose-limiting toxicities</measure>
      <time_frame>Day 28</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Incidence of GVHD related to VCAR33</measure>
      <time_frame>Up to 24 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of patients who achieve response</measure>
      <time_frame>Up to 24 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival post-VCAR33 infusion</measure>
      <time_frame>Up to 24 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression-free survival post-VCAR33 infusion</measure>
      <time_frame>Up to 24 months</time_frame>
    </secondary_outcome>
    <number_of_arms>6</number_of_arms>
    <enrollment type="Anticipated">24</enrollment>
    <condition>Leukemia, Myeloid, Acute</condition>
    <arm_group>
      <arm_group_label>Morphologic Disease: Cohort 1</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>VCAR33 Dose Level 1</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Morphologic Disease: Cohort 2</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>VCAR33 Dose Level 2</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Morphologic Disease: Cohort 3</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>VCAR33 Dose Level 3</description>
    </arm_group>
    <arm_group>
      <arm_group_label>MRD Positive: Cohort 1</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>VCAR33 Dose Level 1</description>
    </arm_group>
    <arm_group>
      <arm_group_label>MRD Positive: Cohort 2</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>VCAR33 Dose Level 2</description>
    </arm_group>
    <arm_group>
      <arm_group_label>MRD Positive: Cohort 3</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>VCAR33 Dose Level 3</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>VCAR33</intervention_name>
      <description>Allogeneic Anti-CD33 Chimeric Antigen Receptor (CAR) T Cell therapy</description>
      <arm_group_label>MRD Positive: Cohort 1</arm_group_label>
      <arm_group_label>MRD Positive: Cohort 2</arm_group_label>
      <arm_group_label>MRD Positive: Cohort 3</arm_group_label>
      <arm_group_label>Morphologic Disease: Cohort 1</arm_group_label>
      <arm_group_label>Morphologic Disease: Cohort 2</arm_group_label>
      <arm_group_label>Morphologic Disease: Cohort 3</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Patients aged ≥18 years&#xD;
  &#xD;
            2. Patients must have CD33+ AML in relapse or refractory after alloHCT&#xD;
  &#xD;
            3. Patients must be a recipient of an 8/8 (A, B, C, DRB1) HLA-matched related or&#xD;
               unrelated donor alloHCT. Patients previously transplanted with VOR33 in the VBP101&#xD;
               study who have R/R AML may also be considered.&#xD;
  &#xD;
            4. Disease status at the time of enrollment:&#xD;
  &#xD;
                 1. Arm A/Morphologic disease: Defined as ≥ 5% blasts (bone marrow) post-HCT&#xD;
  &#xD;
                 2. Arm B/MRD positive: &lt; 5% blasts (bone marrow) with minimal residual disease of at&#xD;
                    least 0.1% CD33+ leukemia cells by flow cytometry&#xD;
  &#xD;
            5. Performance status: ECOG 0 or 1&#xD;
  &#xD;
            6. Patient must have adequate organ function as defined by:&#xD;
  &#xD;
                 1. Cardiac: Left ventricular ejection fraction (LVEF) ≥ 45% or fractional shortening&#xD;
                    ≥ 28%&#xD;
  &#xD;
                 2. Pulmonary: Baseline oxygen saturation &gt; 92% on room air at rest&#xD;
  &#xD;
                 3. Hepatic: Total bilirubin &lt; 3x institutional upper limit of normal (ULN) (except&#xD;
                    in case of patients with documented Gilbert's disease &lt; 5x ULN) and aspartate&#xD;
                    aminotransferase (AST/SGOT)/alanine aminotransferase (ALT/SGPT) &lt; 5x&#xD;
                    institutional ULN&#xD;
  &#xD;
                 4. Renal: Serum creatinine must be ≤ 1.2x institutional ULN or creatinine clearance&#xD;
                    ≥ 60 mL/min for patients with creatinine levels above institutional normal&#xD;
  &#xD;
            7. Original alloHCT donor is available and willing to undergo apheresis&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Patients who have undergone more than one alloHCT&#xD;
  &#xD;
            2. Patients who have undergone alloHCT with a mismatched unrelated donor, haploidentical&#xD;
               donor, or with umbilical cord blood as the stem cell source&#xD;
  &#xD;
            3. Patients who will be less than 100 days post-alloHCT at the time of VCAR33 infusion.&#xD;
  &#xD;
            4. Patients with any history of Grade III or IV acute GVHD or severe chronic GVHD unless&#xD;
               approved by the Sponsor Medical Monitor&#xD;
  &#xD;
            5. Patients with evidence of ongoing active acute or chronic GVHD and are taking systemic&#xD;
               immunosuppressive agents (&gt; 10 mg daily of prednisone equivalent or other&#xD;
               GVHD-directed treatment, including extracorporeal photopheresis). Patients with Grade&#xD;
               1 acute GVHD limited to the skin or mild chronic GVHD limited to the eyes, mouth, or&#xD;
               skin controlled with only topical therapy are eligible.&#xD;
  &#xD;
            6. Patients with active CNS disease. A lumbar puncture is not required to exclude CNS&#xD;
               disease in the absence of clinical signs or symptoms suggesting CNS disease.&#xD;
  &#xD;
            7. Patients with the following prior therapy:&#xD;
  &#xD;
                 1. DLI within 28 days prior to enrollment&#xD;
  &#xD;
                 2. Prior treatment with any CAR T cell therapy product&#xD;
  &#xD;
            8. Patients with active or uncontrolled viral, bacterial, or fungal infection&#xD;
  &#xD;
            9. Patients with a history of a human immunodeficiency virus (HIV) infection or acute or&#xD;
               chronic active hepatitis B or C infection&#xD;
  &#xD;
           10. Patients with a history of malignancy other than nonmelanoma skin cancer or carcinoma&#xD;
               in situ (e.g., cervix, bladder, or breast) unless disease free for at least 3 years&#xD;
               after the last definitive therapy&#xD;
  &#xD;
           11. Female patients of childbearing potential who are pregnant or breastfeeding&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <location>
      <facility>
        <name>University of California San Diego Moores Cancer Center</name>
        <address>
          <city>La Jolla</city>
          <state>California</state>
          <zip>92093</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Michelle Padilla</last_name>
        <phone>858-822-5364</phone>
        <email>mpadilla@health.ucsd.edu</email>
      </contact>
      <investigator>
        <last_name>Divya Koura, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Stanford Cancer Institute</name>
        <address>
          <city>Stanford</city>
          <state>California</state>
          <zip>94305</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Lori Muffly, MD</last_name>
        <phone>650-723-0822</phone>
        <email>lmuffly@stanford.edu</email>
      </contact>
      <investigator>
        <last_name>Lori Muffly, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Miami Cancer Institute</name>
        <address>
          <city>Miami</city>
          <state>Florida</state>
          <zip>33176</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Guenther Koehne, MD, PhD</last_name>
        <phone>786-527-8427</phone>
        <email>guentherk@baptisthealth.net</email>
      </contact>
      <investigator>
        <last_name>Guenther Koehne, MD, PhD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>The University of Kansas Cancer Center</name>
        <address>
          <city>Fairway</city>
          <state>Kansas</state>
          <zip>66205</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Muhammad U Mushtaq, MD</last_name>
        <phone>913-945-6594</phone>
        <email>mmushtaq@kumc.edu</email>
      </contact>
      <investigator>
        <last_name>Muhammad U Mushtaq, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>University of Michigan Health</name>
        <address>
          <city>Ann Arbor</city>
          <state>Michigan</state>
          <zip>48109</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Karmanos Cancer Institute</name>
        <address>
          <city>Detroit</city>
          <state>Michigan</state>
          <zip>48201</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Marie Ventimiglia</last_name>
        <phone>313-576-9271</phone>
        <email>ventimim@karmanos.org</email>
      </contact>
      <investigator>
        <last_name>Abhinav Deol, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Washington University School of Medicine Siteman Cancer Center</name>
        <address>
          <city>Saint Louis</city>
          <state>Missouri</state>
          <zip>63110</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Cathy Wiggins</last_name>
        <phone>314-454-8491</phone>
        <email>cwiggins@wustl.edu</email>
      </contact>
      <investigator>
        <last_name>John DiPersio, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>John Theurer Cancer Center at Hackensack University Medical Center</name>
        <address>
          <city>Hackensack</city>
          <state>New Jersey</state>
          <zip>07601</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Andrew McConnell</last_name>
        <phone>551-996-5949</phone>
        <email>andrew.mcconnell@hmhn.org</email>
      </contact>
      <investigator>
        <last_name>Hyung Suh, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>University Hospitals Seidman Cancer Center</name>
        <address>
          <city>Cleveland</city>
          <state>Ohio</state>
          <zip>44106</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Cancer Information Service Line</last_name>
        <phone>800-641-2422</phone>
        <email>Crystal.Santo@UHhospitals.org</email>
      </contact>
      <investigator>
        <last_name>Brenda Cooper, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>University of Utah Huntsman Cancer Institute</name>
        <address>
          <city>Salt Lake City</city>
          <state>Utah</state>
          <zip>84112</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Catherine Cromar</last_name>
        <phone>801-585-2626</phone>
        <email>Catherine.Cromar@hci.utah.edu</email>
      </contact>
      <investigator>
        <last_name>Brian McClune, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 19, 2023</study_first_submitted>
    <study_first_submitted_qc>August 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 9, 2023</study_first_posted>
    <last_update_submitted>August 14, 2023</last_update_submitted>
    <last_update_submitted_qc>August 14, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Leukemia</keyword>
    <keyword>Acute Myeloid Leukemia</keyword>
    <keyword>AML</keyword>
    <keyword>Hematopoietic stem cell transplant</keyword>
    <keyword>HCT</keyword>
    <keyword>CD33</keyword>
    <keyword>Allogeneic</keyword>
    <keyword>CAR T</keyword>
    <keyword>CAR-T</keyword>
    <keyword>Chimeric Antigen Receptor T Cell</keyword>
    <keyword>CAR T Cells</keyword>
    <keyword>CAR-T Cells</keyword>
    <keyword>Immunotherapy</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Leukemia</mesh_term>
      <mesh_term>Leukemia, Myeloid</mesh_term>
      <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
    </condition_browse>
    <!-- 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/NCT05984199
  org study id: VBP301
  nct id: NCT05984199
  lead sponsor: 
  is fda regulated drug: Yes
  is fda regulated device: No
  This is a Phase 1/2, multicenter, open-label, first-in-human (FIH) study of donor-derived
        anti-CD33 Chimeric Antigen Receptor (CAR) T cell therapy (VCAR33) in patients with relapsed
        or refractory Acute Myeloid Leukemia (AML) after human leukocyte antigen (HLA)-matched
        allogeneic hematopoietic cell transplant (alloHCT).
  CD33 is a preferential target for AML CAR T cell therapy due to its surface expression on the
        majority (>80%) of AML blasts and due to the extensive prior clinical experience
        demonstrating safety and efficacy of targeting CD33 with Mylotarg (gemtuzumab ozogamicin).
        VCAR33 is being developed as a potential new treatment for patients with relapsed/refractory
        (R/R) AML after alloHCT. In this Phase 1/2 trial, the safety and efficacy of
        lentiviral-transduced CD33-directed CAR T cells (VCAR33) generated from the patient's prior
        allogeneic stem cell donor will be tested. It is hypothesized that CAR T cell production from
        healthy donors will not only eliminate delays in production due to lymphopenia but also
        reduce concerns for suboptimal T cell function from exposure to systemic immunosuppression or
        chemotherapeutic agents. Approximately 24 eligible patients with R/R AML after alloHCT will
        be enrolled in one of two separate arms based on disease burden (morphologic disease versus
        measurable residual disease (MRD ) positive). The maximum tolerated dose of VCAR33 will be
        determined using a 3+3 trial design within each arm. Dose escalation can only occur after a
        minimum of 3 patients have completed the dose-limiting toxicity (DLT) observation period.
  allocation: Non-Randomized
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Incidence of dose-limiting toxicities
  time frame: Day 28
  measure: Incidence of GVHD related to VCAR33
  time frame: Up to 24 months
  measure: Percentage of patients who achieve response
  time frame: Up to 24 months
  measure: Overall survival post-VCAR33 infusion
  time frame: Up to 24 months
  measure: Progression-free survival post-VCAR33 infusion
  time frame: Up to 24 months
  arm group label: Morphologic Disease: Cohort 1
  arm group type: Experimental
  description: VCAR33 Dose Level 1
  arm group label: Morphologic Disease: Cohort 2
  arm group type: Experimental
  description: VCAR33 Dose Level 2
  arm group label: Morphologic Disease: Cohort 3
  arm group type: Experimental
  description: VCAR33 Dose Level 3
  arm group label: MRD Positive: Cohort 1
  arm group type: Experimental
  description: VCAR33 Dose Level 1
  arm group label: MRD Positive: Cohort 2
  arm group type: Experimental
  description: VCAR33 Dose Level 2
  arm group label: MRD Positive: Cohort 3
  arm group type: Experimental
  description: VCAR33 Dose Level 3
  intervention type: Biological
  intervention name: VCAR33
  description: Allogeneic Anti-CD33 Chimeric Antigen Receptor (CAR) T Cell therapy
  arm group label: MRD Positive: Cohort 1
  arm group label: MRD Positive: Cohort 2
  arm group label: MRD Positive: Cohort 3
  arm group label: Morphologic Disease: Cohort 1
  arm group label: Morphologic Disease: Cohort 2
  arm group label: Morphologic Disease: Cohort 3
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
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  country: United States
  responsible party type: Sponsor
  mesh term: Leukemia
  mesh term: Leukemia, Myeloid
  mesh term: Leukemia, Myeloid, Acute