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

Sponsor

Innovent Biologics (Suzhou) Co. Ltd. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05280626

Collaborator

(none)

100

Enrollment

Arms

57.2

Anticipated Duration (Months)

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Diffuse Large B-Cell Lymphoma	Drug: Sintilimab Drug: Rituximab	Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Patients with P53 mutation with PD-L1 expressing DLBCL were randomized 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. after 6 cycles, the treatment effective in Group A was maintained with Sindilizumab for 6 months as usual.Patients with P53 mutation with PD-L1 expressing DLBCL were randomized 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. after 6 cycles, the treatment effective in Group A was maintained with Sindilizumab for 6 months as usual.

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Mar 25, 2022

Anticipated Primary Completion Date :

Dec 31, 2025

Anticipated Study Completion Date :

Dec 31, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A: PD-1+R-CHOP After one cycle of standard R-CHOP chemotherapy, Group A uses Sindilizumab + R-CHOP, with Sindilizumab 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.	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. Other Names: Cyclophosphamide Doxorubicin Oncovin Prednisolone Drug: 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. Other Names: Cyclophosphamide Doxorubicin Oncovin Prednisolone
Active Comparator: B: R-CHOP After one cycle of standard R-CHOP chemotherapy, Group B uses R-CHOP and plans for 5 cycles. CR patients in group B are followed up for observation.	Drug: 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. Other Names: Cyclophosphamide Doxorubicin Oncovin Prednisolone

Arm

Intervention/Treatment

Experimental: A: PD-1+R-CHOP

After one cycle of standard R-CHOP chemotherapy, Group A uses Sindilizumab + R-CHOP, with Sindilizumab 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.

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.

Other Names:

Cyclophosphamide

Doxorubicin

Oncovin

Prednisolone

Drug: 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.

Other Names:

Cyclophosphamide

Doxorubicin

Oncovin

Prednisolone

Active Comparator: B: R-CHOP

After one cycle of standard R-CHOP chemotherapy, Group B uses R-CHOP and plans for 5 cycles. CR patients in group B are followed up for observation.

Drug: 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.

Other Names:

Cyclophosphamide

Doxorubicin

Oncovin

Prednisolone

Outcome Measures

Primary Outcome Measures

CRR [1 year]
To assess complete response rate (CRR)

Secondary Outcome Measures

PFS [1 year]
Defined as the time from the beginning of treatment to the first imaging disease progression or death (whichever occurs first).
ORR [1 year]
Objective response rate (ORR)
OS [1 year]
Defined as the time from the start of treatment to the death of the subject due to any cause.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Ages≥18 years, ≤ 80 years.
Patients with primary treatment of DLBCL.
Histopathologically confirmed diagnosis of diffuse large B-cell lymphoma.
At least one measurable lesion according to the 2014 Lugano criteria.
ECOG physical status score of 0, 1 or 2.
Laboratory tests meet the following criteria unless judged to be due to lymphoma:
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.
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.
Coagulation: INR and APTT ≤ 2.5 times the upper limit of normal values.
Consent to use contraception during the trial and for 3 months after its completion.
Expected survival ≥ 3 months.

Exclusion Criteria:

Suffering from other untreated malignant tumours.
Cardiovascular disease that remains unstable under pharmacological control .
With severe interstitial lung disease.
With cognitive impairment.
Patients with uncontrolled autoimmune disease.
Presence of uncontrolled active infection.
Expected survival time < 3 months.
Lactating women and subjects of childbearing age who do not wish to use contraception.
With poor adherence or unable to follow up regularly.