RadiothErapy priMIng for CAR-T

The REMIT Trial is an open label, single arm phase IIa study investigating Radiotherapy as preferred bridging method prior to Tisagenlecleucel treatment in patients with relapsed or refractory Diffuse Large B Cell Lymphoma approved to receive CD19 CAR-T cells as per their licensed indication.

The trial will recruit 20 patients who have been approved to receive Tisagenlecleucel treatment and where the tumour is amendable to radiotherapy as per standard of care.

Trial subjects (patients) during a 14 day screening phase will have their metabolic tumour burden assessed by PET-CT and bridging radiotherapy will be planned. Bridging radiotherapy will commence immediately after leukapheresis with dose adjustments according to disease burden and localisation.

Disease areas requiring effective long-term control will receive full dose radiotherapy, 20 - 30Gy /5-15# and other areas will receive low dose radiotherapy, 4Gy / 2# for optimal tumour debulking and priming effects.

Standard lymphodepletion will be given day -5 to day -3 followed by Tisagenlecleucel infusion on day 0. A window of 14-21 days will be left from last dose of radiotherapy and day 0.

Patients will be followed up at 3 and 6 months after Tisagenlecleucel infusion for a minimum of 12 months.

Inclusion criteria

• Written informed consent
• Age ≥ 18 years
• Histologically proven DLBCL, including transformed follicular or marginal zone lymphoma
• Measurable disease on cross-sectional imaging that is at least 1.5cm in the longest diameter and measurable in two perpendicular dimensions
• Relapsed/refractory after 2 or more standard immuno-chemotherapies
• Approved to receive Tisagenlecleucel as per the licenced indication
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Disease accessible for repeat biopsies (Selected patients only)
• Disease amenable to radiotherapy as assessed by the treating clinical oncologist
• Willing and able to comply with the requirements of the protocol, including contraceptive advice as per the protocol

Exclusion criteria

• Prior radiotherapy at location/dose that would interfere with application of radiotherapy or outcome measures in this trial
• Women who are pregnant or breast feeding
• Previous therapy with any genetically modified autologous or allogeneic T-cell immunotherapy, unless treated with doses of genetically modified autologous or allogeneic T-cell immunotherapy within an abandoned dosing cohort in a first in human dose-escalation phase I clinical trial