Selinexor Combined With Reduced-Dose Radiotherapy For Early-Stage Extranodal NK/T-Cell Lymphoma

Condition(s) studied

Investigational drug(s) / intervention(s)

Pegaspargase (PEG) Asparaginase: Pegaspargase at a dose of 2500 IU/m² (maximum dose not exceeding 3750 IU) is administered via intramuscular injection on Day 1 of each 21-day cycle for a total of 4 cycles.

Gemcitabine (GEM): Gemcitabine 1000 mg/m² is given by intravenous infusion on Day 1 and Day 8 of each 21-day cycle for a total of 4 cycles.

Oxaliplatin: Oxaliplatin 130 mg/m² is administered intravenously on Day 1 of each 21-day cycle for a total of 4 cycles.

Selinexor: Following induction chemotherapy, patients will receive consolidation therapy consisting of selinexor combined with reduced-dose radiotherapy. Selinexor 40 mg will be administered orally twice weekly (Monday and Thursday, Tuesday and Friday, or Wednesday and Saturday). Selinexor will be given concurrently with radiotherapy for a total of 8 doses.

radiotherapy: ollowing induction chemotherapy, patients will receive consolidation therapy consisting of selinexor combined with reduced-dose radiotherapy. Radiotherapy will be delivered at a total dose of 40 Gy in 20 fractions (2 Gy per fraction), once daily, 5 fractions per week, over 4 weeks. Radiation therapy will be performed using intensity-modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT). The target volume includes the gross tumor volume (GTV) of the primary lesion before chemotherapy, with a clinical target volume (CTV) margin expansion of 1-2 cm.

Study summary

Extranodal NK/T-cell lymphoma (ENKTCL) is an Epstein-Barr virus-associated non-Hodgkin lymphoma with high incidence in Asia and Latin America. Approximately 70% of patients present with early-stage (I-II) disease confined to the upper aerodigestive tract. Radiotherapy at 50-56 Gy is the standard curative treatment, but high-dose radiotherapy causes severe toxicities including oral mucositis and xerostomia, while radiotherapy alone yields high systemic recurrence rates. Previous studies have confirmed the efficacy of P-GEMOX induction chemotherapy, verified the feasibility of reduced-dose radiotherapy in patients achieving complete response after chemotherapy, and demonstrated the radiosensitizing effect of selinexor via inhibiting IRF3-BARD1-BRCA1-mediated DNA damage repair. Moreover, international evidence supports the efficacy of 40 Gy radiotherapy combined with chemotherapy. Accordingly, this study hypothesizes that selinexor combined with 40 Gy reduced-dose radiotherapy following P-GEMOX induction chemotherapy can achieve equivalent efficacy to standard-dose radiotherapy, while markedly decreasing radiotherapy-related toxicities. This trial innovatively applies selinexor as a radiosensitizer in ENKTCL, fulfills the unmet clinical demand for efficacy-preserving toxicity reduction, and is well supported by preliminary data.

Eligibility

Primary outcome measure(s)

• Complete response (CR) rate — From the day of initiation of treatment to 8 weeks after completion of radiotherapy.
  CR was defined as complete response evaluated using MRI scan and PET-CT scan according to Lugano criteria.

Trial sites (1)

More Beijing Tongren Hospital trials in China

Other trials for the same condition