Sintilimab, Chidamide, and Azacitidine for Untreated Stage I-II Extranodal NK/T-Cell Lymphoma

A Single-Arm, Multicenter, Phase II Study of Sintilimab Combined With Chidamide and Azacitidine in Patients With Treatment-Naïve Stage I-II Extranodal Natural Killer/T-Cell Lymphoma (SCENT-3)

This is an open-label, single-arm, multi-center Phase II clinical trial evaluating the efficacy and safety of a novel sequential regimen as first-line therapy for treatment-naïve patients with Extranodal NK/T-cell Lymphoma (ENKTL). The study consists of a Screening Phase, a Safety Lead-in Phase, and a Treatment Phase. During the Safety Lead-in Phase, 6 patients will be enrolled to receive a fixed dose of Sintilimab and Chidamide combined with Azacitidine to verify the dose (testing 100mg/d on days 1-3 versus days 1-5). Following the lead-in, all subjects will undergo a 2-cycle Immunotherapy Induction Phase with the SCA regimen (Sintilimab, Chidamide, and Azacitidine). Subsequently, treatment will be stratified based on response: patients achieving Complete Response (CR) or Partial Response (PR) will receive 4 additional cycles of SCA consolidation, while those with Stable Disease (SD) or Progressive Disease (PD) will switch to 4 cycles of P-GemOx chemotherapy. Upon completion of systemic therapy, all patients will undergo consolidative involved-field radiotherapy (≥50Gy).

Inclusion Criteria:

1. Willingness to participate in the clinical study.
2. Age ≥ 18 years at the time of signing the Informed Consent Form (ICF).
3. Newly diagnosed ENKTL confirmed by histopathology at the study center.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
5. At least one evaluable or measurable lesion
6. Ann Arbor stage I-II disease.
7. PINK-E score ≥ 1.
8. Adequate organ and bone marrow function, with no severe hematopoietic dysfunction or abnormalities in cardiac, pulmonary, hepatic, renal, or thyroid function, and no immunodeficiency.

Exclusion Criteria:

1. Aggressive natural killer cell leukemia.
2. Presence of hemophagocytic syndrome.
3. Primary central nervous system (CNS) lymphoma or secondary CNS involvement.
4. Patients with a known history of human immunodeficiency virus (HIV) infection and/or acquired immunodeficiency syndrome (AIDS).
5. Patients with active chronic hepatitis B or active hepatitis C.