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Completed

NCT Number: NCT02893189

CAR19 Donor Lymphocytes for Relapsed CD19+ Malignancies Following Allogeneic Transplantation

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.

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Key information

Conditions

CD19+ Malignancies: Relapse Post-allogeneic Transplant Disease Attributes Pathologic Processes Pathological Conditions, Signs and Symptoms Recurrence

Age range

16 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

University College London Hospital

London, United Kingdom

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age 16-70 years
  • Confirmed diagnosis of CD19+ malignancy relapsing following allogeneic transplantation
  • Agreement to have a pregnancy test, use adequate contraception for 12 months post-final 4G7-CARD T-cell infusion
  • Karnofsky performance status >60
  • Written informed consent

Exclusion criteria

  • Women who are pregnant or lactating
  • Prior history of ischaemic heart disease, dysrhythmias, abnormal ECG (LBBB), Multi Gated Acquisition Scan (MUGA) left ventricular ejection fraction (LVEF<40%) (if performed)
  • Known involvement of the central nervous system or cerebral vascular accident within prior 3 months
  • Patients receiving corticosteroids at a dose of > 10mg prednisolone per day (or equivalent)
  • Active graft versus host disease requiring immunosuppression
  • Use of rituximab within the last 2 months prior to ATIMP infusion
  • Known allergy to albumin or dimethyl sulfoxide (DMSO)
  • Patients who have experienced significant neurotoxicity following blinatumomab treatment

Treatment and study plan

Infusion of modified CAR19 T-cells (4G7-CARD T-cells)

Genetic

The original stem cells donor (or if not available the patient) will undergo unstimulated leucapheresis for generation of the Advanced Therapy Interventional Medicinal Product (ATIMP) 4G7-CARD T-cells. Escalating doses of the ATIMP will then be infused to the patient depending on outcome and any experienced side effects.

Primary outcomes

  1. 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

    The number of ATIMP successfully manufactured would be assessed for all registered patients

  2. Maximum grade for each toxicity type as assessed by CTCAE v4.03, summarized as proportions.

    Time frame: Up to 3 years post final 4G7-CARD T-cell infusion

    Toxicity evaluation following 4G7-CARD T-cell administration as evaluated by the occurrence of adverse events per studied dose using CTCAE v4.03, defined as >grade 2 events that are causally related to study treatment or procedure or Serious Adverse Reactions that require withdrawal of the patient from the study; development and severity of graft-versus-host-disease (GvHD) following cell infusion will also be evaluated as a potential toxicity, as well as development and severity of cytokine release syndrome / macrophage activation syndromes assessed by 'University of Pennsylvania' criteria

Secondary outcomes

  1. 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

    Data for engraftment and expansion would be summarised by mean, median or interquartile ranges and a Kaplan Meier plot for persistence

  2. 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

    Data would be summarised using means (medians) and as the percentage reduction from baseline

  3. 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

    Data on timing (kinetic of change) and magnitude of cytokine levels can be summarised using means (medians) and plots for each patients

Sponsors and collaborators

Lead sponsor

University College, London

Other

Registry information

Official study title

Chimeric Antigen Receptor (CAR)19 Donor Lymphocytes for Relapsed Cluster of Differentiation (CD)19+ Malignancies Following Allogeneic Transplantation (CARD)

Acronym: CARD

Important dates

Study start
2017
Primary completion
2019
Study completion
2022
First posted
Sep 8, 2016
Registry last updated
Jun 22, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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