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

NCT04181489 | Unknown Phase 2 DMC

• 1 other identifier: 2019-SR-271
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 11

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.

Conditions

EBV-Positive DLBCL, Nos

Keywords

Sintilimab; R-CHOP; EBV-Positive DLBCL, nos; treatment-naive

Outcome Measures

Primary Outcomes (1)

• Progressive free survival

  from date of inclusion to date of progression, relapse, or death from any cause

  2 years

Secondary Outcomes (3)

• Overall response rate

  6 months

• Overall survival

  2 years

• Incidence of treatment related adverse events as assessed by NCI-CTCAE 5.0

  2 years

Study Arms (1)

Sintilimab + R-CHOP

EXPERIMENTAL

Drug: Sintilimab; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisolone

Interventions

Sintilimab DRUG

Sintilimab 200mg d0

Sintilimab + R-CHOP

Rituximab DRUG

Rituximab 375 mg/m2 d0

Sintilimab + R-CHOP

Cyclophosphamide DRUG

Cyclophosphamide 750 mg/m2 d1

Sintilimab + R-CHOP

Doxorubicin DRUG

Doxorubicin 50 mg/m2 d1

Sintilimab + R-CHOP

Vincristine DRUG

Vincristine 1.4mg/m2 (maximum 2mg) d1

Sintilimab + R-CHOP

Prednisolone DRUG

Prednisolone 60mg/m2 d1-5

Sintilimab + R-CHOP

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Histologically confirmed EBV-positive diffuse large B cell lymphoma, NOS, according to WHO 2016 criteria.
• \. Understand and voluntarily sign an informed consent form, able to adhere to the study visit schedule and other protocol requirements.
• \. 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:
• 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.
• Hepatic function: total bilirubin less than 1.5-fold of upper normal level; ALT and AST less than 2-fold of upper normal level.
• Renal function: Serum creatine less than 1.5-fold of upper normal level or Ccr ≥ 50 mL/min.
• Cardiac function: New York Heart Association class II or below (EF≥ 50% according to TDE)
• 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;
• 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.

You may not qualify if:

• CNS or meningeal involvement;
• 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;
• Known sensitivity or allergy to investigational product;
• 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;
• Previous allogeneic organ transplantation or allogeneic stem cell transplantation;
• Intention to use any other anti-tumour therapy during treatment;
• Use of systemic anti-tumour treatment within 3 months before first dose of study regimen;
• Active and severe infectious diseases requiring systemic treatment;
• 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)
• 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.
• Active hepatitis B or hepatitis C virus infection, as well as acquired, congenital immune deficiency diseases, including but not limited to HIV-infected persons;
• Previous history of Idiopathic pulmonary fibrosis or Idiopathic pneumonia;
• Active tuberculosis;
• Presence of ≥ Grade 3 immune therapy related toxicity;
• History of mental disorder including epilepsia and dementia;

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

Study Sites (11)

ChangZhou First People's Hospital

Changzhou, Jiangsu, 213003, China

RECRUITING

ChangZhou No.2 People's Hospital

Changzhou, Jiangsu, 213011, China

RECRUITING

HuaiAn First People's Hospital

HuaiAn, Jiangsu, 223300, China

RECRUITING

Drum tower hospital

Nanjing, Jiangsu, 210000, China

RECRUITING

The first Affiliated Hospital Of Nanjing Medical University(JiangSu Province Hospital)

Nanjing, Jiangsu, 21002, China

RECRUITING

The First Affiliated Hospital Of Nantong University

Nantong, Jiangsu, 226000, China

RECRUITING

The Second Affiliated Hospital Of Suzhou University

Suzhou, Jiangsu, 215000, China

RECRUITING

WuXi People's Hospital

Wuxi, Jiangsu, 214023, China

RECRUITING

Xuzhou Central Hospital

Xuzhou, Jiangsu, 221000, China

RECRUITING

Yancheng First People's Hospital

Yancheng, Jiangsu, 224000, China

RECRUITING

ZhenJiang First People's Hospital

Zhenjiang, Jiangsu, 212002, China

RECRUITING

Related Publications (7)

• 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.

  PMID: 26980727 BACKGROUND

• 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.

  PMID: 20548096 BACKGROUND

• 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.

  PMID: 23760676 BACKGROUND

• 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.

  PMID: 24974976 BACKGROUND

• 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.

  PMID: 25475080 BACKGROUND

• 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.

  PMID: 26202875 BACKGROUND

• 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.

  PMID: 29118007 BACKGROUND

MeSH Terms

Conditions

Pyloric Stenosis, Hypertrophic

Interventions

sintilimab; Rituximab; Cyclophosphamide; Doxorubicin; Vincristine; Prednisolone

Condition Hierarchy (Ancestors)

Pyloric Stenosis; Gastric Outlet Obstruction; Stomach Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Study Officials

• Wei Xu, M.D., Ph.D.

  The first Affiliated Hospital Of Nanjing Medical University(JiangSu Province Hospital)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

yi xia, M.D., Ph.D.

CONTACT

025-68306034; cynthia0311@163.com

Wei Xu, M.D., Ph.D.

CONTACT

025-68306034

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 24, 2019
• First Posted: November 29, 2019
• Study Start: January 1, 2019
• Primary Completion: December 30, 2023
• Study Completion: December 30, 2023
• Last Updated: November 29, 2019

Record last verified: 2019-11

Locations

CN (11)