A Study of Ultra-fraction Radiotherapy Bridging CART in R/R DLBCL
Study Details
Study Description
Brief Summary
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: treatment group ultra-fraction radiotherapy + CAR-T |
Radiation: ultra-fraction radiotherapy
the R/R DLBCL patients would receive ultra-fraction radiotherapy as bridging therapy before the CD19 CART cell infusion
|
Outcome Measures
Primary Outcome Measures
- 3-month ORR [3 months]
the overall response rate at 3 months after CAR-T cell infusion
Secondary Outcome Measures
- 2-year PFS [2 years]
the 2-year progression free survival time from CAR-T cell infusion
- 2-year OS [2 years]
the 2-year overall survival time from CAR-T cell infusion
- 6-month ORR [6 months]
the overall response rate at 6 months after CAR-T cell infusion
- DOR [2 years]
the duration of response time
- relapse rate [2 years]
the cumulative rate of relapse
- the rate of severe side effects [2 years]
the rate of severe side effects (CTCAE≥ grade 3）
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Peking Union Medical College Hospital
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- DeSelm C, Palomba ML, Yahalom J, Hamieh M, Eyquem J, Rajasekhar VK, Sadelain M. Low-Dose Radiation Conditioning Enables CAR T Cells to Mitigate Antigen Escape. Mol Ther. 2018 Nov 7;26(11):2542-2552. doi: 10.1016/j.ymthe.2018.09.008. Epub 2018 Sep 13.
- Kuhnl A, Roddie C, Kirkwood AA, Tholouli E, Menne T, Patel A, Besley C, Chaganti S, Sanderson R, O'Reilly M, Norman J, Osborne W, Bloor A, Lugthart S, Malladi R, Patten PEM, Neill L, Martinez-Cibrian N, Kennedy H, Phillips EH, Jones C, Sharplin K, El-Sharkawi D, Latif AL, Mathew A, Uttenthal B, Stewart O, Marzolini MAV, Townsend W, Cwynarski K, Ardeshna K, Ardavan A, Robinson K, Pagliuca A, Collins GP, Johnson R, McMillan A. A national service for delivering CD19 CAR-Tin large B-cell lymphoma - The UK real-world experience. Br J Haematol. 2022 Aug;198(3):492-502. doi: 10.1111/bjh.18209. Epub 2022 Apr 29.
- Manjunath SH, Cohen AD, Lacey SF, Davis MM, Garfall AL, Melenhorst JJ, Maxwell R, Arscott WT, Maity A, Jones JA, Plastaras JP, Stadtmauer EA, Levine BL, June CH, Milone MC, Paydar I. The Safety of Bridging Radiation with Anti-BCMA CAR T-Cell Therapy for Multiple Myeloma. Clin Cancer Res. 2021 Dec 1;27(23):6580-6590. doi: 10.1158/1078-0432.CCR-21-0308. Epub 2021 Sep 15.
- Minn I, Rowe SP, Pomper MG. Enhancing CAR T-cell therapy through cellular imaging and radiotherapy. Lancet Oncol. 2019 Aug;20(8):e443-e451. doi: 10.1016/S1470-2045(19)30461-9. Epub 2019 Jul 29. Review.
- Qu C, Ping N, Kang L, Liu H, Qin S, Wu Q, Chen X, Zhou M, Xia F, Ye A, Kong D, Li C, Yu L, Wu D, Jin Z. Radiation Priming Chimeric Antigen Receptor T-Cell Therapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma With High Tumor Burden. J Immunother. 2020 Jan;43(1):32-37. doi: 10.1097/CJI.0000000000000284.
- Sim AJ, Jain MD, Figura NB, Chavez JC, Shah BD, Khimani F, Lazaryan A, Krivenko G, Davila ML, Liu HD, Falchook AD, Dahiya S, Rapoport AP, Kim S, Locke FL, Robinson TJ. Radiation Therapy as a Bridging Strategy for CAR T Cell Therapy With Axicabtagene Ciloleucel in Diffuse Large B-Cell Lymphoma. Int J Radiat Oncol Biol Phys. 2019 Dec 1;105(5):1012-1021. doi: 10.1016/j.ijrobp.2019.05.065. Epub 2019 Jun 5.
- CART-1