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

Condition(s) studied

Investigational drug(s) / intervention(s)

SCA Induction followed by Response-Adapted Therapy: Drug: Sintilimab, Chidamide, and Azacitidine (SCA Regimen) Safety Lead-in: Patients receive Sintilimab (fixed dose) and Chidamide (fixed dose) combined with Azacitidine at two dose levels (100mg/d on days 1-3 vs. days 1-5) to verify the combination dose. Induction Phase: All enrolled patients receive 2 cycles of SCA induction: Sintilimab (200mg, D1), Chidamide (30mg, biw, D1-21), and Azacitidine (100mg, D1-3/5 \[SCA\]). Cycle length is 21 days. Response-Adapted Consolidation: Patients achieving Complete Response (CR) or Partial Response (PR) continue with 4 cycles of the SCA regimen. Patients with Stable Disease (SD) or Progressive Disease (PD) switch to 4 cycles of P-GemOx chemotherapy (Pemetrexed + Gemcitabine + Oxaliplatin). Radiation: Involved-Field Radiotherapy (IFRT) Following the completion of immunotherapy or chemotherapy, all patients receive local radiotherapy (≥50Gy).

Study summary

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).

Eligibility

Primary outcome measure(s)

• Complete Remission rate — From Baseline to the End of Systemic Treatment or the completion of 6 cycles (each cycle is 21 days), whichever occurs first.
  he Complete Remission (CR) rate is defined as the proportion of participants who achieve a confirmed Complete Remission (CR) during the study treatment period. Tumor response will be assessed by the Investigator according to the Lugano Classification 2014 criteria for malignant lymphoma (or RECIL 2017 if applicable). Complete Remission (CR): Defined as the disappearance of all evidence of disease, including resolution of all target lesions, normalization of lymph nodes (based on size criteria), and metabolic complete response (Deauville Score 1-3) on Positron Emission Tomography-Computed Tomography (PET-CT) scans, if performed. Assessment Schedule: Efficacy assessments (including CT/MRI and PET-CT) will be performed at baseline, at the end of the Induction Phase (after 2 cycles), at the end of Consolidation/Chemotherapy Phase (after 4 additional cycles), and prior to radiotherapy. The best overall response during the systemic therapy phase will be used to calculate the CR rate.

Trial sites (1)

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