First-line Treatment of P53 Mutation With PD-L1 Expression in DLBCL With Anti-PD-1 Mab and R-CHOP

Diffuse Large B-Cell Lymphoma Clinical Trial

Official title:

First-line Treatment of P53 Mutation With PD-L1 Expression in DLBCL With Anti-PD-1 Mab and R-CHOP: a Randomized, Open, Multicenter Clinical Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05280626
• Other study ID #: CIBI308Y047
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: March 25, 2022
• Est. completion date: December 31, 2026

Study information

• Verified date: March 2022
• Source: Innovent Biologics (Suzhou) Co. Ltd.
• Contact: Xiuhua Sun, Master
• Phone: +8617709873631
• Email: sxh17709873631[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma。The majority of refractory patients have PD-L1 expression due to P53 mutations, some of which account for about 10% of DLBCL.Our department has found that in refractory DLBCL with high PD-L1 expression, cedilizumab monotherapy is also more effective and has reversed chemotherapy resistance.The aim of this study was to determine whether the addition of sindilizumab to the R-CHOP regimen could improve the objective efficiency of DLBCL patients with P53 mutation with PD-L1 expression and to see if it could prolong patient survival.

Description:

This study is a randomized, open, multicenter clinical study to determine whether the addition of sindilizumab to the R-CHOP regimen could improve the objective efficiency of DLBCL patients with P53 mutation with PD-L1 expression and to see if it could prolong patient survival.In this study, patients with P53 mutation with PD-L1 expressing DLBCL were selected to be randomised 1:1 into 2 groups: group A Sindilizumab + R-CHOP and group B R-CHOP. Sindilizumab was administered on day 10 after chemotherapy to avoid interference from prednisone.At the end of 6 cycles, Group A treatment effective maintenance treatment with Sindilizumab for 6 months as indicated.Each patient's tumour tissue was tested for mutations and ctDNA after allocation, and ctDNA and peripheral blood free PD-L1 levels were monitored dynamically during and after treatment.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Ages=18 years, = 80 years.

2. Patients with primary treatment of DLBCL.

3. Histopathologically confirmed diagnosis of diffuse large B-cell lymphoma.

4. At least one measurable lesion according to the 2014 Lugano criteria.

5. ECOG physical status score of 0, 1 or 2.

6. Laboratory tests meet the following criteria unless judged to be due to lymphoma:

1. Routine blood tests: (in the absence of growth factor support therapy or blood transfusion within 7 days) haemoglobin = 90 g/L, absolute neutrophil value = 1.5 x 109/L, platelet count = 90 x 109/L.

2. Liver biochemistry: serum creatinine = 1.5 x upper limit of normal; total bilirubin = 1.5 x upper limit of normal; glutamate transaminase and glutamic oxalacetic transaminase = 2.5 x upper limit of normal.

3. Coagulation: INR and APTT = 2.5 times the upper limit of normal values.

7. Consent to use contraception during the trial and for 3 months after its completion.

8. Expected survival = 3 months.

Exclusion Criteria:

1. Suffering from other untreated malignant tumours.

2. Cardiovascular disease that remains unstable under pharmacological control .

3. With severe interstitial lung disease.

4. With cognitive impairment.

5. Patients with uncontrolled autoimmune disease.

6. Presence of uncontrolled active infection.

7. Expected survival time < 3 months.

8. Lactating women and subjects of childbearing age who do not wish to use contraception.

9. With poor adherence or unable to follow up regularly.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Sintilimab
After one cycle of standard R-CHOP chemotherapy, Group A uses Sintilimab with R-CHOP, with Sintilimab administered on day 10 post-chemotherapy, scheduled for 5 cycles. After 5 cycles CR patients in group A continue Sindilizumab treatment for 8 times, once every 21 days.
• Rituximab
After one cycle of standard R-CHOP chemotherapy, Group B uses R-CHOP for 5 cycles. After 5 cycles, CR patients in group B are followed up for observation.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Innovent Biologics (Suzhou) Co. Ltd.

References & Publications (6)

Ansell SM, Minnema MC, Johnson P, Timmerman JM, Armand P, Shipp MA, Rodig SJ, Ligon AH, Roemer MGM, Reddy N, Cohen JB, Assouline S, Poon M, Sharma M, Kato K, Samakoglu S, Sumbul A, Grigg A. Nivolumab for Relapsed/Refractory Diffuse Large B-Cell Lymphoma i — View Citation

Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S, Lefort S, Marit G, Macro M, Sebban C, Belhadj K, Bordessoule D, Fermé C, Tilly H. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing ritux — View Citation

McCord R, Bolen CR, Koeppen H, Kadel EE 3rd, Oestergaard MZ, Nielsen T, Sehn LH, Venstrom JM. PD-L1 and tumor-associated macrophages in de novo DLBCL. Blood Adv. 2019 Feb 26;3(4):531-540. doi: 10.1182/bloodadvances.2018020602. — View Citation

McDermott DF, Atkins MB. PD-1 as a potential target in cancer therapy. Cancer Med. 2013 Oct;2(5):662-73. doi: 10.1002/cam4.106. Epub 2013 Jul 21. Review. — View Citation

Pascual M, Mena-Varas M, Robles EF, Garcia-Barchino MJ, Panizo C, Hervas-Stubbs S, Alignani D, Sagardoy A, Martinez-Ferrandis JI, Bunting KL, Meier S, Sagaert X, Bagnara D, Guruceaga E, Blanco O, Celay J, Martínez-Baztan A, Casares N, Lasarte JJ, MacCarth — View Citation

Young KH, Leroy K, Møller MB, Colleoni GW, Sánchez-Beato M, Kerbauy FR, Haioun C, Eickhoff JC, Young AH, Gaulard P, Piris MA, Oberley TD, Rehrauer WM, Kahl BS, Malter JS, Campo E, Delabie J, Gascoyne RD, Rosenwald A, Rimsza L, Huang J, Braziel RM, Jaffe E — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CRR	To assess complete response rate (CRR)	1 year
Secondary	PFS	Defined as the time from the beginning of treatment to the first imaging disease progression or death (whichever occurs first).	1 year
Secondary	ORR	Objective response rate (ORR)	1 year
Secondary	OS	Defined as the time from the start of treatment to the death of the subject due to any cause.	1 year