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

Phase 2

Not yet recruiting

• Conditions: Diffuse Large B-Cell Lymphoma
• Interventions: Drug: Sintilimab; Drug: Rituximab

• Registration Number: NCT05280626
• Lead Sponsor: Innovent Biologics (Suzhou) Co. Ltd.

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.

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 Timeline

• Status Verified: 2022-03
• Study First Submitted: 2022-03-06
• Study First Submitted QC: 2022-03-06
• Last Update Submitted: 2022-03-06
• Study First Posted: 2022-03-15
• Last Update Posted: 2022-03-15
• Study Start: 2022-03-25
• Primary Completion: 2025-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 100

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A: PD-1+R-CHOP	Sintilimab	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.
A: PD-1+R-CHOP	Rituximab	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.
B: R-CHOP	Rituximab	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.

Primary Outcome Measures

Name	Time	Method
CRR	1 year	To assess complete response rate (CRR)

Secondary Outcome Measures

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