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RadiothErapy priMIng for CAR-T (REMIT)

Primary Purpose

Diffuse Large B Cell Lymphoma

Status
Active
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Bridging Radiotherapy
Sponsored by
University College, London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diffuse Large B Cell Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • St James's University Hospital
  • Kings College Hospital
  • Freeman Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Bridging Radiotherapy

Arm Description

Disease areas requiring effective long-term control will receive full-dose radiotherapy (20-30Gy/5-15#); other areas will receive low dose (4Gy/2#)

Outcomes

Primary Outcome Measures

Percentage of patients starting lymphodepletion on the planned start date without delay
To evaluate whether there is any delay in patients starting lymphodepletion

Secondary Outcome Measures

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)
Overall response rate at 3 months and 6 months after Tisagenlecleucel infusion
Overall response rate after Tisagenlecleucel infusion
Complete metabolic response at 3 months and 6 months after Tisagenlecleucel infusion
Complete metabolic response after Tisagenlecleucel infusion
Duration of response
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
Progression Free Survival after Tisagenlecleucel infusion
Median event-free survival and event-free survival at 12 months
Event-free survival after Tisagenlecleucel infusion
Median overall survival and overall survival at 12 months
Overall Survival after Tisagenlecleucel infusion
Treatment emergent adverse events
Adverse events being reported during and after treatment
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
Neutrophil levels at 1, 3, 6 months after Tisagenlecleucel infusion
Neutrophil counts to be reported after Tisagenlecleucel infusion
Platelet levels at 1, 3, 6 months after Tisagenlecleucel infusion
Platelet counts to be reported after Tisagenlecleucel infusion

Full Information

First Posted
January 20, 2021
Last Updated
July 13, 2023
Sponsor
University College, London
Collaborators
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT04726787
Brief Title
RadiothErapy priMIng for CAR-T
Acronym
REMIT
Official Title
RadiothErapy priMIng for CAR-T
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 18, 2022 (Actual)
Primary Completion Date
August 18, 2023 (Anticipated)
Study Completion Date
August 18, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University College, London
Collaborators
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large B Cell Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Bridging Radiotherapy
Arm Type
Experimental
Arm Description
Disease areas requiring effective long-term control will receive full-dose radiotherapy (20-30Gy/5-15#); other areas will receive low dose (4Gy/2#)
Intervention Type
Radiation
Intervention Name(s)
Bridging Radiotherapy
Intervention Description
Bridging Radiotherapy will start immediately after leukapheresis and before Tisagenlecleucel treatment
Primary Outcome Measure Information:
Title
Percentage of patients starting lymphodepletion on the planned start date without delay
Description
To evaluate whether there is any delay in patients starting lymphodepletion
Time Frame
From planned start date of lymphodepletion until actual start date of lymphodepletion, assessed up to 2 weeks
Secondary Outcome Measure Information:
Title
Best overall response after Tisagenlecleucel infusion as per International Working Group 2014 criteria
Description
Proportion of patients achieving a Complete Response (CR) or Partial Response (PR)
Time Frame
After Tisagenlecleucel infusion through to study completion, an average of 24 months
Title
Overall response rate at 3 months and 6 months after Tisagenlecleucel infusion
Description
Overall response rate after Tisagenlecleucel infusion
Time Frame
At 3 and 6 months after Tisagenlecleucel infusion
Title
Complete metabolic response at 3 months and 6 months after Tisagenlecleucel infusion
Description
Complete metabolic response after Tisagenlecleucel infusion
Time Frame
At 3 and 6 months after Tisagenlecleucel infusion
Title
Duration of response
Description
Time from date of first response confirmation to the first date of progressive disease confirmation
Time Frame
From initial response until the date of first documented disease progression, assessed up to 24 months
Title
Median progression free survival and progression free survival at 12 months
Description
Progression Free Survival after Tisagenlecleucel infusion
Time Frame
12 months after Tisagenlecleucel infusion
Title
Median event-free survival and event-free survival at 12 months
Description
Event-free survival after Tisagenlecleucel infusion
Time Frame
12 months after Tisagenlecleucel infusion
Title
Median overall survival and overall survival at 12 months
Description
Overall Survival after Tisagenlecleucel infusion
Time Frame
12 months after Tisagenlecleucel infusion
Title
Treatment emergent adverse events
Description
Adverse events being reported during and after treatment
Time Frame
From start of Tisagenlecleucel infusion until 30 days post Tisagenlecleucel infusion
Title
Incidence of grade 3 or higher cytokine release syndrome and immune effector cell associated neurotoxicity syndrome
Description
Percentage of grade 3 or higher cytokine relapse syndrome and immune effector cell associated neurotoxicity syndrome events
Time Frame
From start of Tisagenlecleucel infusion through to study completion, an average of 24 months
Title
Neutrophil levels at 1, 3, 6 months after Tisagenlecleucel infusion
Description
Neutrophil counts to be reported after Tisagenlecleucel infusion
Time Frame
At 1, 3 and 6 months after Tisagenlecleucel infusion
Title
Platelet levels at 1, 3, 6 months after Tisagenlecleucel infusion
Description
Platelet counts to be reported after Tisagenlecleucel infusion
Time Frame
At 1, 3 and 6 months after Tisagenlecleucel infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrea Kuhnl
Organizational Affiliation
King's College Hospital NHS Trust
Official's Role
Study Chair
Facility Information:
Facility Name
St James's University Hospital
City
Leeds
Country
United Kingdom
Facility Name
Kings College Hospital
City
London
Country
United Kingdom
Facility Name
Freeman Hospital
City
Newcastle
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

RadiothErapy priMIng for CAR-T

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