A Study of Ultra-fraction Radiotherapy Bridging CART in R/R DLBCL

Study Overview
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Brief Summary
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This is a single-arm single center study to prospectively evaluate the safety and efficacy of ultra-fraction radiotherapy bridging CAR-T therapy in relapsed/refractory diffuse large b cell lymphoma

Official Title
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the Safety and Efficacy of Ultra-fraction Radiotherapy Bridging CART Cell Therapy in Relapsed/Refractory Diffuse Large b Cell Lymphoma

Conditions
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Diffuse Large B Cell Lymphoma, CAR-T, Radiotherapy, Bridging Therapy

Intervention / Treatment
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* Radiation: ultra-fraction radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Over than 18 years old Histologically confirmed DLBCL(by central pathology review before enrolment) Relapsed or refractory disease after ≥2 lines of chemotherapy including rituximab and anthracycline and either having failed autologous Hematopoietic stem cell transplantation (ASCT), or being ineligible for or not consenting to ASCT Measurable disease at time of enrollment (the maximum diameter of cross section ≥1.5cm) Life expectancy ≥12 weeks Able to receive radiotherapy evaluated by specialist Exclusion Criteria: Prior radiation therapy within 1 year of infusion Pregnant or nursing (lactating) women Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion) Previous solid tumor within 3 years, previous or concurrent hematological malignancy Severe organ dysfunction: left ventricle ejection fraction (LVEF) <40%; DLCO <40%; estimated glomerular filtration rate (eGFR)<30mL/min/1.73 m2; total bilirubin >3 ULN HIV positive patients, active replication of or prior infection with hepatitis B or active hepatitis C( HCV RNA positive ); Other conditions that the investigator may exclude due to risks or other possibilities

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment group<br>ultra-fraction radiotherapy + CAR-T | Radiation: ultra-fraction radiotherapy<br>* the R/R DLBCL patients would receive ultra-fraction radiotherapy as bridging therapy before the CD19 CART cell infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-month ORR | the overall response rate at 3 months after CAR-T cell infusion | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year PFS | the 2-year progression free survival time from CAR-T cell infusion | 2 years | 
| 2-year OS | the 2-year overall survival time from CAR-T cell infusion | 2 years | 
| 6-month ORR | the overall response rate at 6 months after CAR-T cell infusion | 6 months | 
| DOR | the duration of response time | 2 years | 
| relapse rate | the cumulative rate of relapse | 2 years | 
| the rate of severe side effects | the rate of severe side effects (CTCAE≥ grade 3） | 2 years |