Sintilimab plus rituximab followed by R-CHOP for untreated primary mediastinal DLBCL

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

This study will see if giving sintilimab with rituximab first, then switching to R-CHOP chemotherapy, helps people newly diagnosed with primary mediastinal diffuse large B‑cell lymphoma get better responses.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, prednisone, sintilimab, rituximab
• Locations: 2 sites (Fuzhou, Fujian and 1 other locations)
• Trial ID: NCT06742502 on ClinicalTrials.gov

What this trial studies

This Phase 2 trial enrolls treatment‑naïve adults with histologically confirmed primary mediastinal DLBCL and gives two cycles of sintilimab plus rituximab followed by PET‑CT. Patients who achieve complete metabolic response after those two cycles receive two more cycles of the immunotherapy combination and then four cycles of R‑CHOP, while others receive six cycles of R‑CHOP. Responders may go on to up to six cycles of maintenance nintedanib, and participants are monitored with PET‑CT and safety assessments throughout treatment. The main outcomes are objective response rates after the immunotherapy combination and after completion of R‑CHOP, along with safety and tolerability.

Who should consider this trial

Good fit: Adults aged 18–75 with newly diagnosed, pathologically confirmed primary mediastinal DLBCL, ECOG 0–2, measurable disease, adequate organ function, and no prior anti-lymphoma therapy are the intended candidates.

Not a fit: Patients with prior lymphoma treatment, severe organ dysfunction, active immunodeficiency, or non‑primary mediastinal DLBCL are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the approach could raise initial response rates and allow some patients to limit chemotherapy exposure by using immunotherapy first.

How similar studies have performed: PD‑1 antibodies have shown activity in primary mediastinal B‑cell lymphoma and combinations of checkpoint inhibitors with anti‑CD20 or chemotherapy have shown promise in related lymphomas, but this exact sintilimab+rituximab then R‑CHOP sequence is relatively new.

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.

Where this trial is running

Fuzhou, Fujian and 1 other locations

• Fujian Cancer Hospital — Fuzhou, Fujian, China (Active_not_recruiting)
• Sun yat-sen university cancer cencer — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Study coordinator: Yan Gao Doctor, Professior

Conditions Primary Mediastinal Diffuse Large B-cell Lymphoma; primary mediastinal diffuse large B-cell lymphoma; PD-1 antibody; R-CHOP