Sintilimab in Combination With R-CHOP in Patients With Treatment-naive EBV-positive DLBCL, NOS

Phase 2

• Conditions: EBV-Positive DLBCL, Nos
• Interventions: Drug: Sintilimab; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisolone

• Registration Number: NCT04181489
• Lead Sponsor: The First Affiliated Hospital with Nanjing Medical University

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-01-01
• Status Verified: 2019-11
• Study First Submitted: 2019-11-24
• Study First Submitted QC: 2019-11-27
• Last Update Submitted: 2019-11-27
• Study First Posted: 2019-11-29
• Last Update Posted: 2019-11-29
• Primary Completion: 2023-12-30
• Study Completion: 2023-12-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 55

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:

4. 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.

5. Hepatic function: total bilirubin less than 1.5-fold of upper normal level; ALT and AST less than 2-fold of upper normal level.

6. Renal function: Serum creatine less than 1.5-fold of upper normal level or Ccr ≥ 50 mL/min.

7. Cardiac function: New York Heart Association class II or below (EF≥ 50% according to TDE)

8. 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;

9. 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Sintilimab + R-CHOP	Cyclophosphamide	-
Sintilimab + R-CHOP	Doxorubicin	-
Sintilimab + R-CHOP	Sintilimab	-
Sintilimab + R-CHOP	Rituximab	-
Sintilimab + R-CHOP	Vincristine	-
Sintilimab + R-CHOP	Prednisolone	-

Primary Outcome Measures

Name	Time	Method
Progressive free survival	2 years	from date of inclusion to date of progression, relapse, or death from any cause

Secondary Outcome Measures

Name	Time	Method
Overall survival	2 years	from the date of inclusion to date of death, irrespective of cause
Overall response rate	6 months	overall response rate after treated by Sintilimab and R-CHOP
Incidence of treatment related adverse events as assessed by NCI-CTCAE 5.0	2 years

Trial Locations

Locations (11)

The first Affiliated Hospital Of Nanjing Medical University(JiangSu Province Hospital); 🇨🇳 NanJing, Jiangsu, China

Drum tower hospital; 🇨🇳 Nanjing, Jiangsu, China

Xuzhou Central Hospital; 🇨🇳 Xuzhou, Jiangsu, China

ZhenJiang First People's Hospital; 🇨🇳 ZhenJiang, Jiangsu, China

ChangZhou First People's Hospital; 🇨🇳 ChangZhou, Jiangsu, China

ChangZhou No.2 People's Hospital; 🇨🇳 ChangZhou, Jiangsu, China

HuaiAn First People's Hospital; 🇨🇳 HuaiAn, Jiangsu, China

The First Affiliated Hospital Of Nantong University; 🇨🇳 Nantong, Jiangsu, China

The Second Affiliated Hospital Of Suzhou University; 🇨🇳 Suzhou, Jiangsu, China

WuXi People's Hospital; 🇨🇳 WuXi, Jiangsu, China

Yancheng First People's Hospital; 🇨🇳 Yancheng, Jiangsu, China