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:

Recruiting

Phase:

Phase 1

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 without pre-conditioning,
      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 will be at least 28 days, following TMG
      confirmation. After the first 3 patients have received dose level 1 the Independent Data
      Management Committee will advise whether the inter-patient dosing interval for subsequent
      patients can be shortened.

      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:Recruiting
    Lead Sponsor:University College, London

    Trial Keywords

    • CD19+
    • allogeneic transplant
    • relapse

    Last Updated