Clinical trial NCT05280626: First-line Treatment of P53 Mutation With PD-L1 Expression in DLBCL With Anti-PD-1 Mab and R-CHOP
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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Diffuse Large B-Cell Lymphoma
Lead sponsor: Innovent Biologics (Suzhou) Co. Ltd.
Sponsor class: INDUSTRY
First posted: 2022-03-15
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: CRR
timeFrame: 1 year
Secondary outcomes:
measure: PFS
timeFrame: 1 year
measure: ORR
timeFrame: 1 year
measure: OS
timeFrame: 1 year
Other outcomes:
Locations:
Study officials:
affiliation: The Second Affiliated Hospital of Dalian Medical University
name: Xiuhua Sun, Master
role: PRINCIPAL_INVESTIGATOR
References:
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