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
Overview
- Phase
- Phase 2
- Intervention
- Sintlimab+Rituximab follwed by R-CHOP(Cyclophosphamide, doxorubicin, vincristine, prednisone)
- Conditions
- Primary Mediastinal Diffuse Large B-cell Lymphoma
- Sponsor
- Sun Yat-sen University
- Enrollment
- 30
- Locations
- 2
- Primary Endpoint
- Complete response rate of Sintilimab combined with rituximab followed by R-CHOP regimen
- Status
- Recruiting
- Last Updated
- 11 months ago
Overview
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:
- Objective response rate of sintilimab combined with rituximab
- 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assessment and will receive 6 cycles of maintenance treatment with nintedanib if CR/CMR/PR is achieved and will be withdrawn from the study if SD/PD occurs.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
Investigators
Huiqiang Huang
Professor
Sun Yat-sen University
Eligibility Criteria
Inclusion Criteria
- •Voluntary participation in clinical study and fully understand, informed consent and sign informed consent form (ICF);
- •Age ≥ 18 years and ≤ 75 years at the time of signing the ICF.
- •treatment-naïve, no anti-lymphoma therapy.
- •Primary mediastinal DLBCL was confirmed histopathologically at the study site.
- •Lugano clinical stage I-IV.
- •International Prognostic Score (IPI) 0-
- •Available tumor tissue samples obtained by previous or fresh core needle aspiration or resection.
- •ECOG score of 0-
- •Expected survival greater than 12 months.
- •Must have at least 1 evaluable or measurable lesion that meets the LYRIC 2016 response evaluation criteria for malignant lymphoma.
Exclusion Criteria
- •Primary central nervous system lymphoma or secondary central nervous system involvement.
- •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.
- •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.
- •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).
- •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.
- •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.
- •Major surgery within 28 days or radiation therapy within 90 days prior to starting study treatment.
- •Anti-cancer Chinese herbal medicine or Chinese patent medicine within 7 days prior to starting study treatment.
- •Administration of live vaccines (except attenuated influenza vaccines) within 28 days prior to starting study treatment.
Arms & Interventions
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.
Intervention: Sintlimab+Rituximab follwed by R-CHOP(Cyclophosphamide, doxorubicin, vincristine, prednisone)
Outcomes
Primary Outcomes
Complete response rate of Sintilimab combined with rituximab followed by R-CHOP regimen
Time Frame: 36 months
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.
Secondary Outcomes
- Objective response rate of Sintilimab combined with rituximab followed by R-CHOP regimen(36 months)
- Progression-free survival of whole cohort(72 months)
- Duration of response in responding patients(72 months)
- Overall survival of whole cohort(72 months)
- Incidence of Adverse event(72 months)