Sintilimab Plus Rituximab Followed by R-CHOP Regimen in Untreated PMBL (Si-Ri)

A Phase II, Multicenter Clinical Study of Sintilimab Combined With Rituximab Followed by R-CHOP Regimen in Patients With Previously Untreated Primary Mediastinal Diffuse Large B-Cell Lymphoma

The goal of this clinical study is to evaluate the efficacy and safety of sintilimab combined with rituximab followed by R-CHOP regimen in treatment-naïve patients with primary mediastinal diffuse large B-cell lymphoma. The main questions it aims to answer are:

1. Objective response rate of sintilimab combined with rituximab
2. Objective response rate after R-CHOP regimen

Study Overview

• Status: Recruiting
• Conditions: Primary Mediastinal Diffuse Large B-cell Lymphoma
• Intervention / Treatment: Drug: Sintlimab+Rituximab follwed by R-CHOP(Cyclophosphamide, doxorubicin, vincristine, prednisone)

Detailed Description

Participants will first receive sintilimab plus rituximab for 2 cycles, followed by interim PET-CT assessments. If patients achieve CR or CMR, they will continue to receive 2 courses of sintilimab plus rituximab, followed by 4 cycles of R-CHOP. Patients will receive 6 courses of R-CHOP if they do not achieve CR or CMR after 2 cycles of sintilimab plus rituximab. Patients will undergo PET-CT assessment and will receive 6 cycles of maintenance treatment with nintedanib if CR/CMR/PR is achieved and will be withdrawn from the study if SD/PD occurs. Total treatment cycles will not exceed 14 cycles

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yan Gao Doctor, Professior; Phone Number: 86 02087343349; Email: gaoyan@sysucc.org.cn

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Active, not recruiting
      • Fujian Cancer Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 51006
      • Recruiting
      • Sun yat-sen university cancer cencer
      • Contact: Jialing Zhuang Doctor, Professor; Phone Number: 02087343350; Email: zhuangjl@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Voluntary participation in clinical study and fully understand, informed consent and sign informed consent form (ICF);
2. Age ≥ 18 years and ≤ 75 years at the time of signing the ICF.
3. treatment-naïve, no anti-lymphoma therapy.
4. Primary mediastinal DLBCL was confirmed histopathologically at the study site.
5. Lugano clinical stage I-IV.
6. International Prognostic Score (IPI) 0-5.
7. Available tumor tissue samples obtained by previous or fresh core needle aspiration or resection.
8. ECOG score of 0-2.
9. Expected survival greater than 12 months.
10. Must have at least 1 evaluable or measurable lesion that meets the LYRIC 2016 response evaluation criteria for malignant lymphoma.
11. Adequate organ and bone marrow function, no severe hematopoietic dysfunction and heart, lung, liver, kidney, thyroid dysfunction and immunodeficiency.
12. Pulse oximetry values > 92% at rest.
13. Women of childbearing potential (WOBCP) must have a negative serum pregnancy test within 7 days before the first dose; WOBCP or men and their WOBCP partners should agree to use effective contraception from signing the ICF until 6 months after the last dose of study drug.

Exclusion Criteria:

1. Primary central nervous system lymphoma or secondary central nervous system involvement.
2. previous treatment with immune checkpoint inhibitors (PD-1, PD-L1, CTLA-4, etc.).

3 History of severe allergic or allergic reactions to humanized or murine monoclonal antibodies.

4. Patients with active autoimmune diseases that require systemic treatment within the past two years; patients with autoimmune diseases that do not require systemic treatment within the past two years may be enrolled.

5. Subjects requiring systemic glucocorticoid therapy or other immunosuppressive therapy for a condition within 14 days prior to starting study treatment [subjects are allowed to be treated with topical, ocular, intra-articular, intranasal, and inhaled glucocorticoids (with minimal systemic absorption); short-term (≤ 7 days) glucocorticoid prophylaxis (e.g., contrast agent allergy) or for the treatment of non-autoimmune diseases (e.g., delayed hypersensitivity due to contact allergens) is allowed]. Low dose steroid debulking therapy for large tumor burden may be excluded (prednisone 30 mg bid × 5 days or equivalent doses of other steroids are allowed).

6. Other malignancies within the past 5 years, except for radically treated cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, breast carcinoma in situ, and cervical carcinoma in situ.

7. Systemic anti-tumor therapy within 28 days before starting study treatment, including chemotherapy, immunotherapy, biological therapy (tumor vaccine, cytokines, or growth factors to control cancer), etc.

8. Major surgery within 28 days or radiation therapy within 90 days prior to starting study treatment.

9. Anti-cancer Chinese herbal medicine or Chinese patent medicine within 7 days prior to starting study treatment.

10. Administration of live vaccines (except attenuated influenza vaccines) within 28 days prior to starting study treatment.

11. Patients with known history of human immunodeficiency virus infection and/or acquired immunodeficiency syndrome.

12. Patients with active chronic hepatitis B or active hepatitis C. Patients who are positive for hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies at screening must be further tested for hepatitis B virus (HBV) DNA titer (not more than 2500 copies/mL or 1000 IU/mL) and HCV RNA (not more than the lower limit of detection of the assay).

13. Any active infection requiring systemic anti-infective therapy within 14 days prior to starting study treatment.

14. Pregnant or lactating women. 15. Have uncontrolled concomitant disease. 19. Patients with a previous history of mental illness; those who are incapacitated or have limited behavioral ability.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Sintilimab plus rituximab followed by R-CHOP regimen; Participants will first receive sintilimab plus rituximab for 2 cycles, followed by interim PET-CT assessments. If patients achieve CR or CMR, they will continue to receive 2 courses of sintilimab plus rituximab, followed by 4 cycles of R-CHOP. Patients will receive 6 courses of R-CHOP if they do not achieve CR or CMR after 2 cycles of sintilimab plus rituximab. Patients will undergo PET-CT assessment and will receive 6 cycles of maintenance treatment with nintedanib if CR/CMR/PR is achieved and will be withdrawn from the study if SD/PD occurs. Total treatment cycles will not exceed 14 cycles.

Drug: Sintlimab+Rituximab follwed by R-CHOP(Cyclophosphamide, doxorubicin, vincristine, prednisone); First strategy of targeted immunotherapy followed by chemotherapy for PMBL. Participants will first receive sintilimab(200mg) plus rituximab(375mg/m2) for 2 cycles. If patients achieve CR or CMR, they will continue to receive 2 courses of sintilimab plus rituximab, followed by 4 cycles of R-CHOP. Patients will receive 6 courses of R-CHOP if they do not achieve CR or CMR after 2 cycles of sintilimab plus rituximab. Patients will undergo PET-CT assessment and will receive 6 cycles of maintenance treatment with nintedanib if CR/CMR/PR is achieved and will be withdrawn from the study if SD/PD occurs. Total treatment cycles will not exceed 14 cycles.; Other Names: CD20 antibody plus PD-1 antibody followed by R-CHOP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response rate of Sintilimab combined with rituximab followed by R-CHOP regimen	Investigator-assessed complete response rate of Sintilimab combined with rituximab followed by R-CHOP regimen. Complete response ratewas determined on the basis of investigator assessments according to the Lymphoma response to immunomodulatory therapy criteria (LYRIC) for Malignant Lymphoma, 2016. Tumor assessments were performed with CT/MRI with or without PET.Complete response was defined as the disappearance of all evidence of disease, regression of measurable disease, and no new sites.	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate of Sintilimab combined with rituximab followed by R-CHOP regimen	Investigator-assessed objective response rate of Sintilimab combined with rituximab followed by R-CHOP regimen. The overall response rate (ORR) including complete response (CR), and partial response (PR) was determined on the basis of investigator assessments according to the Lymphoma response to immunomodulatory therapy criteria (LYRIC) for Malignant Lymphoma, 2016. Tumor assessments were performed with CT/MRI with or without PET.	36 months
Progression-free survival of whole cohort	Progression-free survival time assessed by investigator for sintilimab combined with rituximab followed by R-CHOP regimen. Statistical analysis will entail descriptive statistics, and survival analysis including Kaplan-Meier estimates, log-rank testing of univariate prognostic factors, Cox proportional hazards analysis, as well as T-testing and regression analysis for comparing continuous variables in correlative study data. PFS was defined as time from diagnosis until relapse or progression, non-protocol re-treatment of lymphoma, or death as a result of any cause.	72 months
Duration of response in responding patients	Duration of response to sequential R-CHOP regimen with sintilimab plus rituximab as assessed by the investigator. Duration of response is defined as the time from the date of first occurrence of CR or PR to the date of the first documented PD or death due to any cause.	72 months
Overall survival of whole cohort	Overall survival is defined as the time from the treatment date to the death from any cause.	72 months
Incidence of Adverse event	Safety of sintilimab combined with rituximab followed by R-CHOP regimen. An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.Adverse events will be graded by the investigator according to the NCI-CTCAE Version 5.0	72 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2024
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2029

Study Registration Dates

• First Submitted: December 7, 2024
• First Submitted That Met QC Criteria: December 18, 2024
• First Posted (Actual): December 19, 2024

Study Record Updates

• Last Update Posted (Estimated): June 5, 2025
• Last Update Submitted That Met QC Criteria: June 4, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: R-CHOP; PD-1 antibody; primary mediastinal diffuse large B-cell lymphoma
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Enzyme Inhibitors; Antirheumatic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase Inhibitors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Rituximab; Prednisone; Cyclophosphamide; Doxorubicin; Vincristine; Antibodies
• Other Study ID Numbers: Si-Ri

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Individual participant data may be shared with the consent of all investigators

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No