Phase II Study of Concurrent Tislelizumab and Radiotherapy for Treatment-naïve, Newly Diagnosed Low-risk Extranodal NK/T-cell Lymphoma, Nasal Type
Overview
- Phase
- Phase 2
- Intervention
- Tislelizumab
- Conditions
- Lymphoma
- Sponsor
- Won Seog Kim
- Enrollment
- 38
- Locations
- 1
- Primary Endpoint
- Complete response rate
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This clinical trial intends to analyze the efficacy of PD-1 inhibitor combined with radiotherapy for newly diagnosed NK/T-cell lymphoma. The investigational product in this clinical trial is tislelizumab, a PD-1 inhibitor.
As a rationale for using PD-1 inhibitors in patients with NK/T-cell lymphoma, their efficacy has been proved several times mostly in patients with relapsed NK/T-cell lymphoma.
Patients with low-stage NK/T-cell lymphoma usually receive high-concentration cytotoxic chemotherapy combined with radiotherapy, with treatment response rates of approximately 60 to 80%, but 80-90% of them experience hematological and non-hematologic toxicities during treatment.
Therefore, this study intends to determine the efficacy and safety of PD-1 inhibitor(Tislelizumab) combined with radiotherapy as a first-line therapy compared with pre-existing cytotoxic chemotherapy combined with radiotherapy in patients with NK/T-cell lymphoma with low stage and International Prognostic Index.
Detailed Description
This clinical trial intends to analyze the efficacy of PD-1 inhibitor combined with radiotherapy for newly diagnosed NK/T-cell lymphoma. The investigational product in this clinical trial is tislelizumab, a PD-1 inhibitor. As a rationale for using PD-1 inhibitors in patients with NK/T-cell lymphoma, their efficacy has been proved several times mostly in patients with relapsed NK/T-cell lymphoma. However, a tumor-immune microenvironment(TIME) analysis at our institution confirmed that patients with relapsed or refractory NK/T-cell lymphoma had a peritumoral microenvironment with suppressed activity of T cells and macrophages (immune suppression, IS), in which case the efficacy of PD-1 inhibitor decreased compared to a more immune-active microenvironment (immune evasion or immune tolerance, IE or IT). On the other hand, most patients who were newly diagnosed with NK/T-cell lymphoma had a peritumoral microenvironment with active T cells and macrophages(IE or IT). Patients with low-stage(Stage IE or IIE) NK/T-cell lymphoma usually receive high-concentration cytotoxic chemotherapy combined with radiotherapy, with treatment response rates of approximately 60 to 80%, but 80-90% of them experience grade 3 or 4 hematological and non-hematologic toxicities during treatment. Therefore, based on the tumor microenvironment of NK/T-cell lymphoma, this study intends to determine the efficacy and safety of PD-1 inhibitor(Tislelizumab) combined with radiotherapy as a first-line therapy compared with pre-existing cytotoxic chemotherapy combined with radiotherapy in patients with NK/T-cell lymphoma with low stage and International Prognostic Index.
Investigators
Won Seog Kim
Clinical Professor
Samsung Medical Center
Eligibility Criteria
Inclusion Criteria
- •Histologicallly diagnosed extranodal NK/T-cell lymphoma
- •No history of prior treatment
- •Stage IE/IIE(cases involving the nasal cavity, nasopharynx, and oral cavity only)
- •International prognostic index(PINK, PINK-E risk score): 0-1
- •19 years and older
- •ECOG PS: 0-2
- •AT least one measurable and assessable lesion at least 1.5cm in size on CT or PET/CT scan
- •Adequate bone marrow function, as defined by the following laboratory values(If cytopenia is associated with bone marrow involvement, the subject is excluded):
- •Absolute neutrophil \> 1,500/mm3
- •Hemoglobin \> 9.0g/dL
Exclusion Criteria
- •History of prior treatment(chemotherapy, radiotherapy, or targeted therapy) to treat extranodal NK/T-cell lymphoma
- •Stage III/IV at diagnosis or stage IE-IIE with extranodal(cutaneous, soft tissue, gastrointestinal, brain, spinal cord, bone marrow, etc.)
- •International prognostic index(PINK, PINK-E): ≥ 2
- •Has a concomitant malignancy or had a malignancy(except for appropriately treated basal or squamous cell carcinoma or cervical carcinoma in situ) in the last 3 years prior to initiation of the study treatment
- •Underwent a major surgery within 21 days prior to initiating the study treatment, or has not recovered from serious side effects of surgery
- •Concomitant use of immunosuppressants, except for the following:
- •Intranasal, inhaled, or topical steroid, or local steroid injection(such as intra-articular injection)
- •Physiological dose ≤ 10mg/day of prednisone or equivalent doses of systemic corticosteroid
- •Premedication with steroids to prevent hypersensitivity reaction(such as premedication prior to a CT scan). At the discretion of the investigator, the use of prednisolone at ≥ 10mg for adrenal insufficiency may be acceptable
- •Clinically significant, or active, cardiovascular disease
Arms & Interventions
Tislelizumab therapy
Induction therapy: Tislelizumab combined with radiation Maintenance therapy(after termination of combination therapy)
Intervention: Tislelizumab
Outcomes
Primary Outcomes
Complete response rate
Time Frame: After induction therapy is completed, Every 6 cycles of maintenance, up to 51 months every 6month
The percentage of subjects with complete response(CR)
Overall response rate
Time Frame: After induction therapy is completed, Every 6 cycles of maintenance, up to 51 months every 6month
Secondary Outcomes
- Adverse events(From the day 1 of the clinical trial to 28 days after last drug administration)
- Duration of response(Up to 51 months)
- Progression free-survival(Up to 51 months)
- Overall survival(the time between the date of treatment start and the date of death due to any cause of disease progression assessed up to 51 months)
- Time to response(Up to 51 months)