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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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.
• Препарат 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.

Первичные конечные точки

• CRR [Срок оценки: 1 year]

Вторичные конечные точки (3)

• PFS [Срок оценки: 1 year]
• ORR [Срок оценки: 1 year]
• OS [Срок оценки: 1 year]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

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• 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. PMID 30770362
• 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, Martinez-Baztan A, Casares N, Lasarte JJ, MacCarthy T, Melnick A, Martinez-Climent JA, Roa S. PD-1/PD-L1 immune checkpoint and p53 loss facilitate tumor progression in activated B-cell diffuse la PMID 30975638

Идентификаторы

NCT: NCT05280626 · CIBI308Y047

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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