Sintilimab Plus Rituximab Followed by R-CHOP Regimen in Untreated PMBL

NCT ID: NCT06742502

Last Updated: 2025-06-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-11-12
• Study Completion Date: 2029-12-30

Brief Summary

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

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assessment and will receive 6 cycles of maintenance treatment with nintedanib if CR/CMR/PR is achieved and will be withdrawn from the study if SD/PD occurs.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

Conditions

Primary Mediastinal Diffuse Large B-cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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assessment and will receive 6 cycles of maintenance treatment with nintedanib if CR/CMR/PR is achieved and will be withdrawn from the study if SD/PD occurs.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.

Group Type: EXPERIMENTAL

Sintlimab+Rituximab follwed by R-CHOP(Cyclophosphamide, doxorubicin, vincristine, prednisone)

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

CD20 antibody plus PD-1 antibody followed by R-CHOP

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Huiqiang Huang

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Fujian Cancer Hospital

Fuzhou, Fujian, China

Site Status: ACTIVE_NOT_RECRUITING

Sun yat-sen university cancer cencer

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Yan Gao Doctor, Professior

Role: CONTACT

gaoyan@sysucc.org.cn

86 02087343349

Facility Contacts

Jialing Zhuang Doctor, Professor

Role: primary

zhuangjl@sysucc.org.cn

02087343350

Other Identifiers

Si-Ri

Identifier Type: -

Identifier Source: org_study_id