This is a randomized, open-label, prospective, multicenter phase III superiority study in patients with newly diagnosed stage IV extranodal NK/T-cell lymphoma. The study compares two frontline induction strategies followed by consolidation with autologous hematopoietic stem cell transplantation in patients who achieve a protocol-defined strict complete remission.
Eligible participants will be randomized 1:1 to Arm A or Arm B, stratified by three-level PINK-E risk category. Arm A consists of one cycle of GELAD induction followed by three cycles of MEDA chemotherapy. Participants who achieve strict complete remission after key response assessment will proceed to autologous hematopoietic stem cell transplantation consolidation. Arm B consists of four cycles of LEAP induction with sintilimab, pegaspargase, and anlotinib. Participants who achieve strict complete remission will receive high-dose methotrexate CNS-directed consolidation followed by autologous hematopoietic stem cell transplantation consolidation if eligible.
The primary endpoint is event-free survival within 24 months after randomization. Secondary endpoints include progression-free survival, overall survival, overall response rate, complete remission rate, strict complete remission rate, autologous hematopoietic stem cell transplantation completion rate, cumulative incidence of relapse, grade 3 or higher adverse events, treatment discontinuation, treatment-related mortality, and plasma EBV-DNA clearance dynamics.
Age 18 to 70 years at the time of signing informed consent.
Histologically confirmed extranodal NK/T-cell lymphoma according to the current classification criteria, with tumor tissue confirmed to be EBER positive. Central pathology review is recommended.
Stage IV disease according to Lugano 2014 staging criteria, with baseline staging including PET/CT and bone marrow evaluation.
Previously untreated disease, with no prior systemic anti-lymphoma therapy, radiotherapy, or other anti-tumor treatment for NKTCL.
Prior systemic anti-lymphoma therapy, radiotherapy, or investigational anti-tumor therapy.
Active central nervous system lymphoma involvement, including active brain parenchymal, meningeal, cerebrospinal fluid, or intraocular involvement.
Active infection requiring intensive care support, or infection judged by the investigator to be uncontrolled and likely to significantly interfere with protocol treatment.
Known history of acute or chronic pancreatitis, or any condition judged by the investigator to be an absolute contraindication to pegaspargase.
Rong Tao
Lead sponsor
Fudan University
Sponsor institution