CAR19 Donor Lymphocytes for Relapsed CD19+ Malignancies Following Allogeneic Transplantation (CARD)

University College London (UCL)

Status and phase: Completed; Phase 1

Conditions: CD19+ Malignancies: Relapse Post-allogeneic Transplant

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

Study type: Interventional

Funder types: Other

Identifiers

NCT02893189

UCL16/0045

Details and patient eligibility

About

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.

Full 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.

Enrollment: 17 patients

Sex: All

Ages: 16 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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17 participants in 1 patient group

4G7-CARD T-cells

Experimental group

Description:

All patient will receive modified CAR19 T-cells.

Treatment:

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