RadiothErapy priMIng for CAR-T

Diffuse Large B Cell Lymphoma Clinical Trial

— REMIT  

Official title:

RadiothErapy priMIng for CAR-T

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04726787
• Other study ID #: UCL/137861
• Status: Active, not recruiting
• Phase: N/A
• Start date: August 18, 2022
• Est. completion date: May 31, 2024

Study information

• Verified date: November 2023
• Source: University College, London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 6
• Est. completion date: May 31, 2024
• Est. primary completion date: July 5, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diffuse Large B Cell Lymphoma
• Lymphoma, Large B-Cell, Diffuse

Intervention

Radiation:
• Bridging Radiotherapy
Bridging Radiotherapy will start immediately after leukapheresis and before Tisagenlecleucel treatment

Locations

Country	Name	City	State
United Kingdom	St James's University Hospital	Leeds
United Kingdom	Kings College Hospital	London
United Kingdom	Freeman Hospital	Newcastle

Sponsors (2)

Lead Sponsor	Collaborator
University College, London	Novartis Pharmaceuticals

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Median progression free survival and progression free survival at 12 months	Progression Free Survival after Tisagenlecleucel infusion	12 months after Tisagenlecleucel infusion
Secondary	Median event-free survival and event-free survival at 12 months	Event-free survival after Tisagenlecleucel infusion	12 months after Tisagenlecleucel infusion
Secondary	Median overall survival and overall survival at 12 months	Overall Survival after Tisagenlecleucel infusion	12 months after Tisagenlecleucel infusion
Secondary	Treatment emergent adverse events	Adverse events being reported during and after treatment	From start of Tisagenlecleucel infusion until 30 days post Tisagenlecleucel infusion
Secondary	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
Secondary	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
Secondary	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