Clinical trial NCT04181489: Sintilimab in Combination With R-CHOP in Patients With Treatment-naive EBV-positive DLBCL, NOS
Official title: A Phase II, Prospective, Multi-center Study of Sintilimab in Combination With R-CHOP in Patients With Treatment-naive EBV-positive DLBCL, NOS
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: EBV-Positive DLBCL, Nos
Keywords: Sintilimab
R-CHOP
EBV-Positive DLBCL, nos
treatment-naive
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
First posted: 2019-11-29
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The prognosis of EBV+ DLBCL is dismal. Previous study showed that high level of PD-L1 expression in EBV+ DLBCL. The investigators therefore design this phase II study to investigate the safety and efficacy of sintilimab (an anti-PD-1 antibody) in combination with R-CHOP in patients with treatment-naive EBV+ DLBCL.


Eligibility criteria: Inclusion Criteria:

1. Histologically confirmed EBV-positive diffuse large B cell lymphoma, NOS, according to WHO 2016 criteria.

2. Understand and voluntarily sign an informed consent form, able to adhere to the study visit schedule and other protocol requirements.

3. Undergo whole-body PET/CT scan 28 days before enrolment and have a measurable or evaluable disease (nodal lesion: diameter ≥ 1.5cm; extranodal lesion≥1.0cm）according to Lugano 2014 criteria； 4. ECOG PS 0- 2; 5. Adequate organ function, defined as:

1. Blood routine test: neutrophil count ≥ 1.0×10⁹/L, platelet count ≥ 50×10⁹/L, hemoglobulin ≥8.0g/dL, without G-CSF usage or blood infusion within 7 days before examination.
2. Hepatic function: total bilirubin less than 1.5-fold of upper normal level; ALT and AST less than 2-fold of upper normal level.
3. Renal function: Serum creatine less than 1.5-fold of upper normal level or Ccr ≥ 50 mL/min.
4. Cardiac function: New York Heart Association class II or below (EF≥ 50% according to TDE)
5. Coagulative function: INR less than 1.5-fold of upper normal level, APTT less than 10s above upper normal level and PT less than 3s above upper normal level;
6. Thyroid function: normal baseline TSH level, or abnormal baseline TSH but normal T3/T4 level without symptoms; 6. Expected survival ≥ 3 months; 7. Age 18\~70 years; 8. Female subjects in childbearing age, their serum or urine pregnancy test must be negative. All patients must agree to take effective contraceptive measures during treatment and 90 days after treatment.

Exclusion Criteria:

1. CNS or meningeal involvement;
2. Patients with secondary tumour, excluding cured (5 years without relapse) in situ Non-melanoma skin cancer. superficial bladder cancer, in situ cervical cancer, Gastrointestinal intramucous carcinoma and breast cancer;
3. Known sensitivity or allergy to investigational product;
4. Previous exposure to anti PD-1 antibody, anti PD-L1 antibody, anti PD-L2 antibody, anti CTLA-4 antibody, CAR-T therapy or any T cell co-stimulating antibody or checkpoint inhibitor;
5. Previous allogeneic organ transplantation or allogeneic stem cell transplantation;
6. Intention to use any other anti-tumour therapy during treatment;
7. Use of systemic anti-tumour treatment within 3 months before first dose of study regimen;
8. Active and severe infectious diseases requiring systemic treatment;
9. Active (known or suspected) autoimmune disease or history of autoimmune disease within 2 years before treatment (excluding patients with leukoderma, psoriasis, lipsotrichia or Grave's disease who do not require systemic treatment within 2 years, patients with hypothyrea only requiring thyroxine as treatment, and patients with type I diabetes but only requiring insulin treatment)
10. Usage of immune inhibitory drugs 4 weeks before the first dose of study regimen, excluding local usage of glucocorticoid and systemic usage of less than 10mg/d Prednisone or equivalent glucocorticoid.
11. Active hepatitis B or hepatitis C virus infection, as well as acquired, congenital immune deficiency diseases, including but not limited to HIV-infected persons;
12. Previous history of Idiopathic pulmonary fibrosis or Idiopathic pneumonia;
13. Active tuberculosis;
14. Presence of ≥ Grade 3 immune therapy related toxicity;
15. History of mental disorder including epilepsia and dementia;
16. Any anti-infectious vital vaccine usage 4 weeks before the first dose or during treatment;
17. Any potential drug abuse, medical, psychological or social conditions which may disturb this investigation and assessment;
18. Women who are pregnant or lactating.
19. Usage of other experimental drugs within 1 month before treatment;
20. In any conditions which investigator considered ineligible for this study

Primary outcomes:
measure: Progressive free survival
timeFrame: 2 years
Secondary outcomes:
measure: Overall response rate
timeFrame: 6 months
measure: Overall survival
timeFrame: 2 years
measure: Incidence of treatment related adverse events as assessed by NCI-CTCAE 5.0
timeFrame: 2 years
Other outcomes:
Locations:
city: ChangZhou
country: China
facility: ChangZhou First People's Hospital
state: Jiangsu
city: ChangZhou
country: China
facility: ChangZhou No.2 People's Hospital
state: Jiangsu
city: HuaiAn
country: China
facility: HuaiAn First People's Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Drum tower hospital
state: Jiangsu
city: NanJing
country: China
facility: The first Affiliated Hospital Of Nanjing Medical University(JiangSu Province Hospital)
state: Jiangsu
city: Nantong
country: China
facility: The First Affiliated Hospital Of Nantong University
state: Jiangsu
city: Suzhou
country: China
facility: The Second Affiliated Hospital Of Suzhou University
state: Jiangsu
city: WuXi
country: China
facility: WuXi People's Hospital
state: Jiangsu
city: Xuzhou
country: China
facility: Xuzhou Central Hospital
state: Jiangsu
city: Yancheng
country: China
facility: Yancheng First People's Hospital
state: Jiangsu
city: ZhenJiang
country: China
facility: ZhenJiang First People's Hospital
state: Jiangsu
Study officials:
affiliation: The first Affiliated Hospital Of Nanjing Medical University(JiangSu Province Hospital)
name: Wei Xu, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, Advani R, Ghielmini M, Salles GA, Zelenetz AD, Jaffe ES. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016 May 19;127(20):2375-90. doi: 10.1182/blood-2016-01-643569. Epub 2016 Mar 15.
citation: Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S, Lefort S, Marit G, Macro M, Sebban C, Belhadj K, Bordessoule D, Ferme C, Tilly H. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte. Blood. 2010 Sep 23;116(12):2040-5. doi: 10.1182/blood-2010-03-276246. Epub 2010 Jun 14.
citation: Ahn JS, Yang DH, Duk Choi Y, Jung SH, Yhim HY, Kwak JY, Sung Park H, Shin MG, Kim YK, Kim HJ, Lee JJ. Clinical outcome of elderly patients with Epstein-Barr virus positive diffuse large B-cell lymphoma treated with a combination of rituximab and CHOP chemotherapy. Am J Hematol. 2013 Sep;88(9):774-9. doi: 10.1002/ajh.23507. Epub 2013 Jul 23.
citation: Sato A, Nakamura N, Kojima M, Ohmachi K, Carreras J, Kikuti YY, Numata H, Ohgiya D, Tazume K, Amaki J, Moriuchi M, Miyamoto M, Aoyama Y, Kawai H, Ichiki A, Hara R, Kawada H, Ogawa Y, Ando K. Clinical outcome of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly in the rituximab era. Cancer Sci. 2014 Sep;105(9):1170-5. doi: 10.1111/cas.12467. Epub 2014 Sep 8.
citation: Hong JY, Yoon DH, Suh C, Huh J, Do IG, Sohn I, Jo J, Jung SH, Hong ME, Yoon H, Ko YH, Kim SJ, Kim WS. EBV-positive diffuse large B-cell lymphoma in young adults: is this a distinct disease entity? Ann Oncol. 2015 Mar;26(3):548-55. doi: 10.1093/annonc/mdu556. Epub 2014 Dec 4.
citation: Lu TX, Liang JH, Miao Y, Fan L, Wang L, Qu XY, Cao L, Gong QX, Wang Z, Zhang ZH, Xu W, Li JY. Epstein-Barr virus positive diffuse large B-cell lymphoma predict poor outcome, regardless of the age. Sci Rep. 2015 Jul 23;5:12168. doi: 10.1038/srep12168.
citation: Xu-Monette ZY, Zhou J, Young KH. PD-1 expression and clinical PD-1 blockade in B-cell lymphomas. Blood. 2018 Jan 4;131(1):68-83. doi: 10.1182/blood-2017-07-740993. Epub 2017 Nov 8.