Anti-PD-1 Antibody Alone or in Combination With Decitabine/Chemotherapy in Relapsed or Refractory Malignancies

Официальное название

Anti-PD-1 Antibody Alone or in Combination With Low-dose Decitabine and/or Chemotherapy in Relapsed or Refractory Malignancies: an Open-label Phase I/II Trial

Обзор

The purpose of this study is to assess the feasibility, safety, and efficacy of anti-PD-1 antibody alone or in combination with low-dose decitabine in patients with relapsed or refractory malignancies, including Non-Hodgkin'lymphoma, Hodgkin'lymphoma, gastrointestinal cancers, hepatocellular carcinoma, breast cancer, ovarian cancer or lung cancer or renal-cell cancer or pancreatic cancer or bile duct cancer.

Подробное описание

Primary objective: To assess the feasibility and safety for Anti-PD-1 antibody alone or in combination with decitabine and/or chemotherapy administered every 3 weeks to subjects with relapsed or refractory malignancies.

Secondary objectives: 1) To assess the antitumor activity of Anti-PD-1 antibody alone or in combination with decitabine and/or chemotherapy in subjects with relapsed or refractory malignancies. 2) To characterize the immunological effects of Anti-PD-1 antibody alone or in combination with decitabine and/or chemotherapy. 3) To characterize the immunological effects of Anti-PD-1 antibody alone or in combination with decitabine and/or chemotherapy.

Exploratory objectives: 1) To analysis of potential biological parameters correlated to clinical response and toxicities. 2) To search predictive biomarkers to guide the choose of patients undergoing the treatment of Anti-PD-1 antibody alone or in combination with decitabine and/or chemotherapy.

Safety Evaluation: Adverse events will be assessed continuously during the study and for 100 days post last treatment, and will be evaluated according to the NCI CTCAE Version 4.0.

Efficacy Evaluation: 1) Treatment response to lymphoma was defined using the International Workshop to Standardize Response Criteria for Lymphomas; 2) Treatment response to solid tumors was defined using Response Evaluation Criteria in Solid Tumors (RECIST1.1).

evaluation index: BOR; ORR; PFS and OS.

Вмешательства

• Препарат Anti-PD-1 antibody
  Anti-PD-1 antibody will be given at 1-3mg/kg on day8 by IV every three weeks
• Препарат Decitabine
  Decitabine will be given at 10mg/d on day 1to 5 by IV every three weeks
• Препарат Chemotherapy
  Chemotherapy be given depends on the cancer type and treatment regimen before enrollment.

Первичные конечные точки

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0. [Срок оценки: 2 years]

Вторичные конечные точки (4)

• Objective response by Response Evaluation Criteria in Solid Tumors (RECIST1.1). [Срок оценки: 3 years]
• Objective response by the International Workshop to Standardize Response Criteria for lymphomas. [Срок оценки: 3 years]
• Progression free survival [Срок оценки: 5 years]
• Overall survival [Срок оценки: 5 years]

Критерии участия

Критерии включения

• Subjects must have histological confirmation of relapsed or refractory malignancies,including Non-Hodgkin'lymphoma, Hodgkin'lymphoma, gastrointestinal cancers, hepatocellular carcinoma, breast cancer, ovarian cancer or lung cancer or renal-cell cancer or pancreatic cancer or bile duct cancer.
• 12 to 75 years of age.
• ECOG performance of less than 2.
• Life expectancy of at least 3 months.
• Subjects with lymphoma must have at least one measureable lesion >1 cm as defined by lymphoma response criteria; with solid tumors must have at least one measureable lesion >1 cm per RECIST1.1.
• Subjects must have received at least two prior chemotherapy regimen, and must be off therapy for at least 4 weeks prior to Day 1. Subjects with autologous hematopoietic stem-cell transplantation are eligible which must be more than 3 months.
• Subjects must have adequate bone marrow, live, renal, lung and heart functions.

• Absolute neutrophil count greater than or equal to 1,000/μL.
• Platelet count greater than or equal to 70,000/µL.
• Serum bilirubin level less than or equal to 1.5 x upper limits of normal (ULN).
• Serum creatinine less than or equal to 1.5 x ULN.
• Alanine aminotransferase \[ALT or SGPT\] and aspartate aminotransferase \[AST or SGOT\] less than or equal to 2.5 x ULN.

Критерии исключения

• Subjects with any autoimmune disease or history of syndrome that requires corticosteroids or immunosuppressive medications.
• Serious uncontrolled medical disorders or active infections, pulmonary and intestinal infection especially.
• Active alimentary tract hemorrhage or history of alimentary tract hemorrhage in 1 month .
• Prior organ allograft.
• Women who are pregnant or breastfeeding.
• Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.

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

Китай · 1 центр

• Biotherapeutic Department of Chinese PLA General Hospital — Пекин

Публикации

• Mei Q, Chen M, Lu X, Li X, Duan F, Wang M, Luo G, Han W. An open-label, single-arm, phase I/II study of lower-dose decitabine based therapy in patients with advanced hepatocellular carcinoma. Oncotarget. 2015 Jun 30;6(18):16698-711. doi: 10.18632/oncotarget.3677. PMID 25895027
• Nie J, Zhang Y, Li X, Chen M, Liu C, Han W. DNA demethylating agent decitabine broadens the peripheral T cell receptor repertoire. Oncotarget. 2016 Jun 21;7(25):37882-37892. doi: 10.18632/oncotarget.9352. PMID 27191266
• Liu Y, Wang C, Li X, Dong L, Yang Q, Chen M, Shi F, Brock M, Liu M, Mei Q, Liu J, Nie J, Han W. Improved clinical outcome in a randomized phase II study of anti-PD-1 camrelizumab plus decitabine in relapsed/refractory Hodgkin lymphoma. J Immunother Cancer. 2021 Apr;9(4):e002347. doi: 10.1136/jitc-2021-002347. PMID 33820822
• Wang C, Liu Y, Dong L, Li X, Yang Q, Brock MV, Mei Q, Liu J, Chen M, Shi F, Liu M, Nie J, Han W. Efficacy of Decitabine plus Anti-PD-1 Camrelizumab in Patients with Hodgkin Lymphoma Who Progressed or Relapsed after PD-1 Blockade Monotherapy. Clin Cancer Res. 2021 May 15;27(10):2782-2791. doi: 10.1158/1078-0432.CCR-21-0133. Epub 2021 Mar 5. PMID 33674274
• Nie J, Wang C, Liu Y, Yang Q, Mei Q, Dong L, Li X, Liu J, Ku W, Zhang Y, Chen M, An X, Shi L, Brock MV, Bai J, Han W. Addition of Low-Dose Decitabine to Anti-PD-1 Antibody Camrelizumab in Relapsed/Refractory Classical Hodgkin Lymphoma. J Clin Oncol. 2019 Jun 10;37(17):1479-1489. doi: 10.1200/JCO.18.02151. Epub 2019 Apr 30. PMID 31039052

Идентификаторы

NCT: NCT02961101 · CHN-PLAGH-BT-019

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗