Clinical Trials /

CAR19 Donor Lymphocytes for Relapsed CD19+ Malignancies Following Allogeneic Transplantation

NCT02893189

Description:

Eligible patients will receive escalating doses of 4G7-CARD T-cells paralleling clinical standard of care with unmanipulated donor lymphocytes. There are 3 intra-patient dose levels planned. Patients will be followed up regularly during the interventional phase of the study until 12 months post-final 4G7-CARD T-cell infusion. Thereafter patients will be followed up annually for years 2 and 3.

Related Conditions:
  • Hematopoietic and Lymphoid Malignancy
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT02893189

Trial Eligibility

Document

Title

  • Brief Title: CAR19 Donor Lymphocytes for Relapsed CD19+ Malignancies Following Allogeneic Transplantation
  • Official Title: Chimeric Antigen Receptor (CAR)19 Donor Lymphocytes for Relapsed Cluster of Differentiation (CD)19+ Malignancies Following Allogeneic Transplantation (CARD)

Clinical Trial IDs

  • ORG STUDY ID: UCL16/0045
  • NCT ID: NCT02893189

Conditions

  • CD19+ Malignancies: Relapse Post-allogeneic Transplant

Purpose

Eligible patients will receive escalating doses of 4G7-CARD T-cells paralleling clinical standard of care with unmanipulated donor lymphocytes. There are 3 intra-patient dose levels planned. Patients will be followed up regularly during the interventional phase of the study until 12 months post-final 4G7-CARD T-cell infusion. Thereafter patients will be followed up annually for years 2 and 3.

Detailed Description

      Patients will receive escalating doses of 4G7-CARD T-cells (after pre-conditioning with
      Fludarabine and Cyclophosphamide), paralleling clinical standard of care with unmanipulated
      donor lymphocytes. Intra-patient dose escalation will proceed at intervals of not less than 8
      weeks, dependent on development of toxicity or evidence of efficacy and confirmation by the
      Trial Management Group.

      Three dose cohorts levels are planned, and dosing will be according to total CD3+ T- cell
      dose as this correlates with toxicity in the unmanipualated donor lymphocyte setting:

        -  Dose Level 1: 1x10^6 CD3+ T-cells/kg (starting dose for all patients)

        -  Dose Level 2: 3x10^6 CD3+ T-cells/kg

        -  Dose Level 3: 1x10^7 CD3+ T-cells/kg

      The inter-patient dosing for the first 3 patients was at least 28 days, following TMG
      confirmation.

      Patients will be followed up regularly during the interventional phase of the study until 12
      months post-final 4G7-CARD T-cell infusion. During the long term follow up phase of the study
      (years 2-3 post-final 4G7-CARD T-cell infusion) patients will be followed-up annually for
      overall survival, disease status and safety.

      All patients will enter long term follow up until 3 years post-final 4G7-CARD T-cell
      infusion.

Trial Arms

NameTypeDescriptionInterventions
4G7-CARD T-cellsExperimentalAll patient will receive modified CAR19 T-cells.

    Eligibility Criteria

            Inclusion Criteria:

          1. Age 16-70 years

          2. Confirmed diagnosis of CD19+ malignancy relapsing following allogeneic transplantation

          3. Agreement to have a pregnancy test, use adequate contraception for 12 months
             post-final 4G7-CARD T-cell infusion

          4. Karnofsky performance status >60

          5. Written informed consent

        Exclusion Criteria:

          1. Women who are pregnant or lactating

          2. Prior history of ischaemic heart disease, dysrhythmias, abnormal ECG (LBBB), Multi
             Gated Acquisition Scan (MUGA) left ventricular ejection fraction (LVEF<40%) (if
             performed)

          3. Known involvement of the central nervous system or cerebral vascular accident within
             prior 3 months

          4. Patients receiving corticosteroids at a dose of > 10mg prednisolone per day (or
             equivalent)

          5. Active graft versus host disease requiring immunosuppression

          6. Use of rituximab within the last 2 months prior to ATIMP infusion

          7. Known allergy to albumin or dimethyl sulfoxide (DMSO)

          8. Patients who have experienced significant neurotoxicity following blinatumomab
             treatment
    Maximum Eligible Age:70 Years
    Minimum Eligible Age:16 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Feasibility of generation of 4G7-CARD T-cells using the ProdigyTM system
    Time Frame:Through patient registration and manufacturing period, an average of 18 months from start of trial
    Safety Issue:
    Description:The number of ATIMP successfully manufactured would be assessed for all registered patients

    Secondary Outcome Measures

    Measure:Assessment of engraftment, expansion and persistence of the 4G7-CARD T-cells as determined by quantitative polymerase chain reaction (qPCR) or flow cytometry
    Time Frame:Sampling occurs at days 0, 4, 6, 11, 18, plus months 1, 2, 3, 6, 9 and 1 year post final 4G7-CARD T-cell infusion
    Safety Issue:
    Description:Data for engraftment and expansion would be summarised by mean, median or interquartile ranges and a Kaplan Meier plot for persistence
    Measure:Assessing the depletion of B cell compartment, as determined by flow cytometry
    Time Frame:Sampling occurs at days 0, 4, 6, 11, 18, plus months 1, 2, 3, 6, 9 and 1 year post final 4G7-CARD T-cell infusion
    Safety Issue:
    Description:Data would be summarised using means (medians) and as the percentage reduction from baseline
    Measure:Assessing the timing and magnitude of cytokine release, evaluated using Cytokine bead arrays
    Time Frame:Sampling occurs at days 0, 4, 6, 11, 18, plus 1 month post final 4G7-CARD T-cell infusion
    Safety Issue:
    Description:Data on timing (kinetic of change) and magnitude of cytokine levels can be summarised using means (medians) and plots for each patients

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Active, not recruiting
    Lead Sponsor:University College, London

    Trial Keywords

    • CD19+
    • allogeneic transplant
    • relapse

    Last Updated

    June 18, 2021