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/NCT05990751</url>
    </required_header>
    <id_info>
      <org_study_id>UCL\142424</org_study_id>
      <nct_id>NCT05990751</nct_id>
    </id_info>
    <brief_title>Multi-modular Chimeric Antigen Receptor Targeting GD2 in Neuroblastoma</brief_title>
    <acronym>MAGNETO</acronym>
    <official_title>Multi-modular Chimeric Antigen Receptor Targeting GD2 in Neuroblastoma</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University College, London</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University College, London</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        MAGNETO is a single-centre, non-randomised, open label Phase I clinical trial of an Advanced&#xD;
        Therapy Investigational Medicinal Product (ATIMP) in children and teenagers aged 1-16 years&#xD;
        with relapsed or refractory neuroblastoma.&#xD;
  &#xD;
        The study will assess the feasibility of generating the ATIMP (GD2 CAR T cells) and the&#xD;
        safety of administering the ATIMP in patients with relapsed or refractory neuroblastoma.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        MAGNETO is a single-centre, non-randomised, open label Phase I clinical trial of an Advanced&#xD;
        Therapy Investigational Medicinal Product (ATIMP) in children and teenagers aged 1-16 years&#xD;
        with neuroblastoma.&#xD;
  &#xD;
        The ATIMP for this study (GD2 CAR T cells) are autologous T cells, modified to express GD2&#xD;
        CAR (targeting GD2 on the neuroblastoma cells) and additional transgenes aiming to confer&#xD;
        resistance to inhibition in the tumour microenvironment and to support CAR T cell function&#xD;
        and persistence.&#xD;
  &#xD;
        Patients will undergo an unstimulated leucapheresis for the generation of the ATIMP which&#xD;
        will take approximately 15 days to generate.&#xD;
  &#xD;
        Patients will receive lymphodepleting (LD) chemotherapy with fludarabine 30 mg/m2&#xD;
        administered over 4 days (Day -6 to Day -3) and cyclophosphamide 500 mg/m2 administered over&#xD;
        2 days (Day -4 and Day-3).&#xD;
  &#xD;
        Patients will be treated at one of the three dose levels (Dose Level 1: 30 x 10^6 CAR T&#xD;
        cells/m2; Dose Level 2: 100 x 10^6 CAR T cells/m2; Dose Level 3: 300 x 10^6 CAR T cells/m2)&#xD;
        following LD chemotherapy as described above.&#xD;
  &#xD;
        The study will evaluate the feasibility of generating the ATIMP, the safety of administering&#xD;
        ATIMP, the tolerability of the ATIMP and how effectively the CAR T cells engraft, expand and&#xD;
        persist following administration in patients with neuroblastoma.&#xD;
  &#xD;
        Following infusion of the CAR T cells, patients will be monitored for between 2-4 weeks as an&#xD;
        inpatient. Following discharge, patients will enter the interventional follow up phase and be&#xD;
        followed up for 1 year. Patients will be seen at 6 weeks post infusion then 3 monthly until 1&#xD;
        year post CAR T cells infusion.&#xD;
  &#xD;
        If patients relapse within the first-year post CAR T cell infusion, they will come off the&#xD;
        interventional follow up and will be followed up annually until 15 years after the CAR T&#xD;
        infusion.&#xD;
  &#xD;
        After completing the 1-year interventional phase of the study, all patients, irrespective of&#xD;
        whether they progressed or responded to treatment, will enter long term follow up until 15&#xD;
        years post CAR T infusion.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">January 2024</start_date>
    <completion_date type="Anticipated">December 2041</completion_date>
    <primary_completion_date type="Anticipated">December 2026</primary_completion_date>
    <phase>Phase 1</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>Safety of administering the ATIMP</measure>
      <time_frame>28 days</time_frame>
      <description>Incidence of grade 3-5 toxicity causally related to the ATIMP, particularly severe cytokine release syndrome and severe neurotoxicity.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Feasibility of manufacturing the ATIMP</measure>
      <time_frame>28 days</time_frame>
      <description>Feasibility of generation of the ATIMP as evaluated by the number of therapeutic products generated and the number of ATIMPs infused after successful manufacture.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Objective response rate</measure>
      <time_frame>1 year</time_frame>
      <description>Based on cross-sectional imaging and semi-quantitative assessment on 123I-MIBG after the ATIMP intravenous administration</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression Free Survival (PFS)</measure>
      <time_frame>1 year</time_frame>
      <description>Progression Free Survival (PFS) after the ATIMP intravenous administration</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to Progression (TTP)</measure>
      <time_frame>1 year</time_frame>
      <description>Time to Progression (TTP) after the ATIMP intravenous administration</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival</measure>
      <time_frame>1 year</time_frame>
      <description>Overall Survival after the ATIMP intravenous administration</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">12</enrollment>
    <condition>Neuroblastoma</condition>
    <arm_group>
      <arm_group_label>GD2 CAR T cells</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Treatment with GD2 CAR T cells</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>GD2 CAR T cells</intervention_name>
      <description>The GD2 CAR T cells target GD2 positive cells. The cells also express transgenes that aim to increase their resistance within the tumour microenvironment.</description>
      <arm_group_label>GD2 CAR T cells</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Age ≥ 1 and ≤ 16 years.&#xD;
  &#xD;
            2. Tissue diagnosis of neuroblastoma. If sufficient biopsy material is available, GD2&#xD;
               expression on the tumour will be confirmed. As GD2 is consistently expressed in&#xD;
               neuroblastoma demonstration of GD2 is not mandated.&#xD;
  &#xD;
            3. Relapsed or refractory disease after one or multiple lines of previous treatment.&#xD;
  &#xD;
            4. Measurable disease by cross sectional imaging or evaluable disease by uptake on&#xD;
               123I-MIBG scan. Patients with only bone marrow detectable disease (bone marrow&#xD;
               aspirate or trephine) are NOT eligible for the study.&#xD;
  &#xD;
            5. At least 3 weeks or 5 half-lives, whichever is shorter, after treatment with agents on&#xD;
               other early phase clinical trial.&#xD;
  &#xD;
            6. Performance status: Karnofsky (age ≥ 10 years) or Lansky (age &lt; 10) score ≥ 50%.&#xD;
               Patients who are unable to walk because of paralysis, but who are able to sit upright&#xD;
               unassisted in a wheelchair, will be considered ambulatory for the purpose of assessing&#xD;
               performance score.&#xD;
  &#xD;
            7. Creatinine ≤1.5 ULN for age, if higher, an estimated (calculated) creatinine clearance&#xD;
               must be ≥ 60 ml/min/1.73 m2.&#xD;
  &#xD;
            8. Absolute lymphocyte count ≥ 0.25 x 10^9/L.&#xD;
  &#xD;
            9. For post-pubertal subjects agreement to have a pregnancy test, use adequate&#xD;
               contraception (if applicable).&#xD;
  &#xD;
           10. Written informed consent.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Patients with only bone marrow detectable disease in the absence of measurable disease&#xD;
               by cross sectional imaging or evaluable disease by uptake on 123I-MIBG scan.&#xD;
  &#xD;
            2. Patients with active, inoperative CNS disease including leptomeningeal disease.&#xD;
  &#xD;
            3. Active hepatitis B, C or HIV infection.&#xD;
  &#xD;
            4. Inability to tolerate leukapheresis.&#xD;
  &#xD;
            5. Clinically significant systemic illness or medical condition (e.g., significant&#xD;
               cardiac, pulmonary, hepatic or other organ dysfunction), that in the judgement of the&#xD;
               investigator is likely to interfere with assessment of safety or efficacy of the&#xD;
               investigational regimen and its requirements.&#xD;
  &#xD;
            6. Any contraindication to lymphodepletion or to the use of Cyclophosphamide or&#xD;
               Fludarabine as per the local SmPC.&#xD;
  &#xD;
            7. Any contraindication to the use of Anticoagulant Citrate Dextrose Solution.&#xD;
  &#xD;
            8. Known allergy to albumin, EDTA or DMSO.&#xD;
  &#xD;
            9. Primary immunodeficiency or history of autoimmune disease (e.g., Crohn's, rheumatoid&#xD;
               arthritis, systemic lupus) requiring systemic immunosuppression /systemic disease&#xD;
               modifying agents within the last 2 years.&#xD;
  &#xD;
           10. Prior treatment with investigational or approved gene therapy or cell therapy&#xD;
               products.&#xD;
  &#xD;
           11. Life expectancy &lt;3 months.&#xD;
  &#xD;
           12. Use of rituximab (or rituximab biosimilar) within the last 3 months prior to of GD2&#xD;
               CAR T cells infusion.&#xD;
  &#xD;
           13. Systemic corticosteroid therapy ≥ 0.05 mg/kg dexamethasone daily (or equivalent) at&#xD;
               time of GD2 CAR T cells infusion.&#xD;
  &#xD;
           14. Post-pubertal subjects who are pregnant or breastfeeding.&#xD;
  &#xD;
          Exclusion criteria for the ATIMP infusion:&#xD;
  &#xD;
            1. Uncontrolled fungal, bacterial, viral, or other infection. Previously diagnosed&#xD;
               infection for which the patient continues to receive antimicrobial therapy is&#xD;
               permitted if responding to treatment and clinically stable at the time of scheduled&#xD;
               GD2 CAR T cells infusion.&#xD;
  &#xD;
            2. Systemic corticosteroid therapy ≥ 0.05 mg/kg dexamethasone daily (or equivalent) at&#xD;
               time of GD2 CAR T cells infusion.&#xD;
  &#xD;
            3. Use of rituximab (or rituximab biosimilar) within the last 3 months prior to GD2 CAR T&#xD;
               cell infusion&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>1 Year</minimum_age>
      <maximum_age>16 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>MAGNETO Trial Coordinator</last_name>
      <phone>+442076799379</phone>
      <email>ctc.magneto@ucl.ac.uk</email>
    </overall_contact>
    <verification_date>June 2023</verification_date>
    <study_first_submitted>August 5, 2023</study_first_submitted>
    <study_first_submitted_qc>August 5, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 5, 2023</last_update_submitted>
    <last_update_submitted_qc>August 5, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>neuroblastoma</keyword>
    <keyword>CAR T cells</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Neuroblastoma</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/NCT05990751
  org study id: UCL\142424
  nct id: NCT05990751
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  MAGNETO is a single-centre, non-randomised, open label Phase I clinical trial of an Advanced
        Therapy Investigational Medicinal Product (ATIMP) in children and teenagers aged 1-16 years
        with relapsed or refractory neuroblastoma.
  
        The study will assess the feasibility of generating the ATIMP (GD2 CAR T cells) and the
        safety of administering the ATIMP in patients with relapsed or refractory neuroblastoma.
  MAGNETO is a single-centre, non-randomised, open label Phase I clinical trial of an Advanced
        Therapy Investigational Medicinal Product (ATIMP) in children and teenagers aged 1-16 years
        with neuroblastoma.
  
        The ATIMP for this study (GD2 CAR T cells) are autologous T cells, modified to express GD2
        CAR (targeting GD2 on the neuroblastoma cells) and additional transgenes aiming to confer
        resistance to inhibition in the tumour microenvironment and to support CAR T cell function
        and persistence.
  
        Patients will undergo an unstimulated leucapheresis for the generation of the ATIMP which
        will take approximately 15 days to generate.
  
        Patients will receive lymphodepleting (LD) chemotherapy with fludarabine 30 mg/m2
        administered over 4 days (Day -6 to Day -3) and cyclophosphamide 500 mg/m2 administered over
        2 days (Day -4 and Day-3).
  
        Patients will be treated at one of the three dose levels (Dose Level 1: 30 x 10^6 CAR T
        cells/m2; Dose Level 2: 100 x 10^6 CAR T cells/m2; Dose Level 3: 300 x 10^6 CAR T cells/m2)
        following LD chemotherapy as described above.
  
        The study will evaluate the feasibility of generating the ATIMP, the safety of administering
        ATIMP, the tolerability of the ATIMP and how effectively the CAR T cells engraft, expand and
        persist following administration in patients with neuroblastoma.
  
        Following infusion of the CAR T cells, patients will be monitored for between 2-4 weeks as an
        inpatient. Following discharge, patients will enter the interventional follow up phase and be
        followed up for 1 year. Patients will be seen at 6 weeks post infusion then 3 monthly until 1
        year post CAR T cells infusion.
  
        If patients relapse within the first-year post CAR T cell infusion, they will come off the
        interventional follow up and will be followed up annually until 15 years after the CAR T
        infusion.
  
        After completing the 1-year interventional phase of the study, all patients, irrespective of
        whether they progressed or responded to treatment, will enter long term follow up until 15
        years post CAR T infusion.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Safety of administering the ATIMP
  time frame: 28 days
  description: Incidence of grade 3-5 toxicity causally related to the ATIMP, particularly severe cytokine release syndrome and severe neurotoxicity.
  measure: Feasibility of manufacturing the ATIMP
  time frame: 28 days
  description: Feasibility of generation of the ATIMP as evaluated by the number of therapeutic products generated and the number of ATIMPs infused after successful manufacture.
  measure: Objective response rate
  time frame: 1 year
  description: Based on cross-sectional imaging and semi-quantitative assessment on 123I-MIBG after the ATIMP intravenous administration
  measure: Progression Free Survival (PFS)
  time frame: 1 year
  description: Progression Free Survival (PFS) after the ATIMP intravenous administration
  measure: Time to Progression (TTP)
  time frame: 1 year
  description: Time to Progression (TTP) after the ATIMP intravenous administration
  measure: Overall survival
  time frame: 1 year
  description: Overall Survival after the ATIMP intravenous administration
  arm group label: GD2 CAR T cells
  arm group type: Experimental
  description: Treatment with GD2 CAR T cells
  intervention type: Biological
  intervention name: GD2 CAR T cells
  description: The GD2 CAR T cells target GD2 positive cells. The cells also express transgenes that aim to increase their resistance within the tumour microenvironment.
  arm group label: GD2 CAR T cells
  criteria: 
  gender: All
  minimum age: 1 Year
  maximum age: 16 Years
  healthy volunteers: No
  last name: MAGNETO Trial Coordinator
  phone: +442076799379
  email: ctc.magneto@ucl.ac.uk
  responsible party type: Sponsor
  mesh term: Neuroblastoma