Clinical trial NCT04726787: RadiothErapy priMIng for CAR-T
Official title: RadiothErapy priMIng for CAR-T
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Diffuse Large B Cell Lymphoma
Lead sponsor: University College, London
Sponsor class: OTHER
Collaborators: name: Novartis Pharmaceuticals
First posted: 2021-01-27
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of patients starting lymphodepletion on the planned start date without delay
timeFrame: From planned start date of lymphodepletion until actual start date of lymphodepletion, assessed up to 2 weeks
Secondary outcomes:
measure: Best overall response after Tisagenlecleucel infusion as per International Working Group 2014 criteria
timeFrame: After Tisagenlecleucel infusion through to study completion, an average of 24 months
measure: Overall response rate at 3 months and 6 months after Tisagenlecleucel infusion
timeFrame: At 3 and 6 months after Tisagenlecleucel infusion
measure: Complete metabolic response at 3 months and 6 months after Tisagenlecleucel infusion
timeFrame: At 3 and 6 months after Tisagenlecleucel infusion
measure: Duration of response
timeFrame: From initial response until the date of first documented disease progression, assessed up to 24 months
measure: Median progression free survival and progression free survival at 12 months
timeFrame: 12 months after Tisagenlecleucel infusion
measure: Median event-free survival and event-free survival at 12 months
timeFrame: 12 months after Tisagenlecleucel infusion
measure: Median overall survival and overall survival at 12 months
timeFrame: 12 months after Tisagenlecleucel infusion
measure: Treatment emergent adverse events
timeFrame: From start of Tisagenlecleucel infusion until 30 days post Tisagenlecleucel infusion
measure: Incidence of grade 3 or higher cytokine release syndrome and immune effector cell associated neurotoxicity syndrome
timeFrame: From start of Tisagenlecleucel infusion through to study completion, an average of 24 months
measure: Neutrophil levels at 1, 3, 6 months after Tisagenlecleucel infusion
timeFrame: At 1, 3 and 6 months after Tisagenlecleucel infusion
measure: Platelet levels at 1, 3, 6 months after Tisagenlecleucel infusion
timeFrame: At 1, 3 and 6 months after Tisagenlecleucel infusion
Other outcomes:
Locations:
city: Leeds
country: United Kingdom
facility: St James's University Hospital
city: London
country: United Kingdom
facility: Kings College Hospital
city: Newcastle
country: United Kingdom
facility: Freeman Hospital
Study officials:
affiliation: King's College Hospital NHS Trust
name: Andrea Kuhnl
role: STUDY_CHAIR
References: