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

Diffuse Large B Cell Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05514327
• Other study ID #: CART-1
• Status: Recruiting
• Phase: N/A
• Start date: September 1, 2022
• Est. completion date: December 1, 2024

Study information

• Verified date: January 2024
• Source: Peking Union Medical College Hospital
• Contact: Jing Ruan, Docter
• Phone: +8615201435860
• Email: ruanjing[@]pumch.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 1, 2024
• Est. primary completion date: September 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• CAR-T
• Diffuse Large B Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Radiotherapy

Intervention

Radiation:
• ultra-fraction radiotherapy
the R/R DLBCL patients would receive ultra-fraction radiotherapy as bridging therapy before the CD19 CART cell infusion

Locations

Country	Name	City	State
China	Peking Union Medical College Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital

Country where clinical trial is conducted

China, 

References & Publications (6)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	3-month ORR	the overall response rate at 3 months after CAR-T cell infusion	3 months
Secondary	2-year PFS	the 2-year progression free survival time from CAR-T cell infusion	2 years
Secondary	2-year OS	the 2-year overall survival time from CAR-T cell infusion	2 years
Secondary	6-month ORR	the overall response rate at 6 months after CAR-T cell infusion	6 months
Secondary	DOR	the duration of response time	2 years
Secondary	relapse rate	the cumulative rate of relapse	2 years
Secondary	the rate of severe side effects	the rate of severe side effects (CTCAE= grade 3)	2 years