Clinical trial NCT05514327: A Study of Ultra-fraction Radiotherapy Bridging CART in R/R DLBCL
Official title: the Safety and Efficacy of Ultra-fraction Radiotherapy Bridging CART Cell Therapy in Relapsed/Refractory Diffuse Large b Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Diffuse Large B Cell Lymphoma
CAR-T
Radiotherapy
Bridging Therapy
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2022-08-24
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria:

1. Over than 18 years old
2. Histologically confirmed DLBCL(by central pathology review before enrolment)
3. 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
4. Measurable disease at time of enrollment (the maximum diameter of cross section ≥1.5cm)
5. Life expectancy ≥12 weeks
6. Able to receive radiotherapy evaluated by specialist

Exclusion Criteria:

1. Prior radiation therapy within 1 year of infusion
2. Pregnant or nursing (lactating) women
3. Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
4. Previous solid tumor within 3 years, previous or concurrent hematological malignancy
5. 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
6. HIV positive patients, active replication of or prior infection with hepatitis B or active hepatitis C( HCV RNA positive );
7. Other conditions that the investigator may exclude due to risks or other possibilities

Primary outcomes:
measure: 3-month ORR
timeFrame: 3 months
Secondary outcomes:
measure: 2-year PFS
timeFrame: 2 years
measure: 2-year OS
timeFrame: 2 years
measure: 6-month ORR
timeFrame: 6 months
measure: DOR
timeFrame: 2 years
measure: relapse rate
timeFrame: 2 years
measure: the rate of severe side effects
timeFrame: 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.