RadiothErapy priMIng for CAR-T (REMIT)

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

Study Overview

• Status: Active, not recruiting
• Conditions: Diffuse Large B Cell Lymphoma
• Intervention / Treatment: Radiation: Bridging Radiotherapy

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Leeds, United Kingdom
    • St James's University Hospital
  • London, United Kingdom
    • Kings College Hospital
  • Newcastle, United Kingdom
    • Freeman Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bridging Radiotherapy; Disease areas requiring effective long-term control will receive full-dose radiotherapy (20-30Gy/5-15#); other areas will receive low dose (4Gy/2#)	Radiation: Bridging Radiotherapy; Bridging Radiotherapy will start immediately after leukapheresis and before Tisagenlecleucel treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients starting lymphodepletion on the planned start date without delay	To evaluate whether there is any delay in patients starting lymphodepletion	From planned start date of lymphodepletion until actual start date of lymphodepletion, assessed up to 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best overall response after Tisagenlecleucel infusion as per International Working Group 2014 criteria	Proportion of patients achieving a Complete Response (CR) or Partial Response (PR)	After Tisagenlecleucel infusion through to study completion, an average of 24 months
Overall response rate at 3 months and 6 months after Tisagenlecleucel infusion	Overall response rate after Tisagenlecleucel infusion	At 3 and 6 months after Tisagenlecleucel infusion
Complete metabolic response at 3 months and 6 months after Tisagenlecleucel infusion	Complete metabolic response after Tisagenlecleucel infusion	At 3 and 6 months after Tisagenlecleucel infusion
Duration of response	Time from date of first response confirmation to the first date of progressive disease confirmation	From initial response until the date of first documented disease progression, assessed up to 24 months
Median progression free survival and progression free survival at 12 months	Progression Free Survival after Tisagenlecleucel infusion	12 months after Tisagenlecleucel infusion
Median event-free survival and event-free survival at 12 months	Event-free survival after Tisagenlecleucel infusion	12 months after Tisagenlecleucel infusion
Median overall survival and overall survival at 12 months	Overall Survival after Tisagenlecleucel infusion	12 months after Tisagenlecleucel infusion
Treatment emergent adverse events	Adverse events being reported during and after treatment	From start of Tisagenlecleucel infusion until 30 days post Tisagenlecleucel infusion
Incidence of grade 3 or higher cytokine release syndrome and immune effector cell associated neurotoxicity syndrome	Percentage of grade 3 or higher cytokine relapse syndrome and immune effector cell associated neurotoxicity syndrome events	From start of Tisagenlecleucel infusion through to study completion, an average of 24 months
Neutrophil levels at 1, 3, 6 months after Tisagenlecleucel infusion	Neutrophil counts to be reported after Tisagenlecleucel infusion	At 1, 3 and 6 months after Tisagenlecleucel infusion
Platelet levels at 1, 3, 6 months after Tisagenlecleucel infusion	Platelet counts to be reported after Tisagenlecleucel infusion	At 1, 3 and 6 months after Tisagenlecleucel infusion

Collaborators and Investigators

• Sponsor: University College, London
• Collaborators: Novartis Pharmaceuticals
• Investigators: Study Chair: Andrea Kuhnl, King's College Hospital NHS Trust

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2022
• Primary Completion (Actual): July 5, 2023
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: January 20, 2021
• First Submitted That Met QC Criteria: January 25, 2021
• First Posted (Actual): January 27, 2021

Study Record Updates

• Last Update Posted (Actual): December 9, 2024
• Last Update Submitted That Met QC Criteria: December 4, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Lymphoma, Large B-Cell, Diffuse
• Other Study ID Numbers: UCL/137861

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No