Diffuse Large B Cell Lymphoma
Conditions
Brief summary
The REMIT trial will investigate radiotherapy as a preferred bridging method prior to Tisagenlecleucel infusion in patients with relapsed or refractory Diffuse Large B Cell Lymphoma
Detailed description
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.
Interventions
RADIATIONBridging Radiotherapy
Bridging Radiotherapy will start immediately after leukapheresis and before Tisagenlecleucel treatment
Sponsors
Novartis Pharmaceuticals
University College, London
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Written informed consent 2. Age ≥ 18 years 3. Histologically proven DLBCL, including transformed follicular or marginal zone lymphoma 4. Measurable disease on cross-sectional imaging that is at least 1.5cm in the longest diameter and measurable in two perpendicular dimensions 5. Relapsed/refractory after 2 or more standard immuno-chemotherapies 6. Approved to receive Tisagenlecleucel as per the licenced indication 7. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 8. Disease accessible for repeat biopsies (Selected patients only) 9. Disease amenable to radiotherapy as assessed by the treating clinical oncologist 10. Willing and able to comply with the requirements of the protocol, including contraceptive advice as per the protocol
Exclusion criteria
1. Prior radiotherapy at location/dose that would interfere with application of radiotherapy or outcome measures in this trial 2. Women who are pregnant or breast feeding 3. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of patients starting lymphodepletion on the planned start date without delay | From planned start date of lymphodepletion until actual start date of lymphodepletion, assessed up to 2 weeks | To evaluate whether there is any delay in patients starting lymphodepletion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate at 3 months and 6 months after Tisagenlecleucel infusion | At 3 and 6 months after Tisagenlecleucel infusion | Overall response rate after Tisagenlecleucel infusion |
| Complete metabolic response at 3 months and 6 months after Tisagenlecleucel infusion | At 3 and 6 months after Tisagenlecleucel infusion | Complete metabolic response after Tisagenlecleucel infusion |
| Duration of response | From initial response until the date of first documented disease progression, assessed up to 24 months | Time from date of first response confirmation to the first date of progressive disease confirmation |
| Median progression free survival and progression free survival at 12 months | 12 months after Tisagenlecleucel infusion | Progression Free Survival after Tisagenlecleucel infusion |
| Median event-free survival and event-free survival at 12 months | 12 months after Tisagenlecleucel infusion | Event-free survival after Tisagenlecleucel infusion |
| Best overall response after Tisagenlecleucel infusion as per International Working Group 2014 criteria | After Tisagenlecleucel infusion through to study completion, an average of 24 months | Proportion of patients achieving a Complete Response (CR) or Partial Response (PR) |
| Treatment emergent adverse events | From start of Tisagenlecleucel infusion until 30 days post Tisagenlecleucel infusion | Adverse events being reported during and after treatment |
| Platelet levels at 1, 3, 6 months after Tisagenlecleucel infusion | At 1, 3 and 6 months after Tisagenlecleucel infusion | Platelet counts to be reported after Tisagenlecleucel infusion |
| Incidence of grade 3 or higher cytokine release syndrome and immune effector cell associated neurotoxicity syndrome | From start of Tisagenlecleucel infusion through to study completion, an average of 24 months | Percentage of grade 3 or higher cytokine relapse syndrome and immune effector cell associated neurotoxicity syndrome events |
| Neutrophil levels at 1, 3, 6 months after Tisagenlecleucel infusion | At 1, 3 and 6 months after Tisagenlecleucel infusion | Neutrophil counts to be reported after Tisagenlecleucel infusion |
| Median overall survival and overall survival at 12 months | 12 months after Tisagenlecleucel infusion | Overall Survival after Tisagenlecleucel infusion |
Countries
United Kingdom
Outcome results
None listed