Sintilimab, Chidamide, and Azacitidine for Untreated Stage I-II Extranodal NK/T-Cell Lymphoma (SCENT-3)

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Adverse Event; Overall Survival; Progression Free Survival; Duration of Response; Complete Remission Rate， CRR
• Intervention / Treatment: Drug: SCA Induction followed by Response-Adapted Therapy

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Huiqiang Huang, Ph.D.; Phone Number: 020-87343009; Email: huanghq@sysucc.org.cn

Study Locations

• China
  • Guangzhou, China
    • Sun Yat-sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Experimental: 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).

Drug: 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Remission rate	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.	From Baseline to the End of Systemic Treatment or the completion of 6 cycles (each cycle is 21 days), whichever occurs first.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
objective response rate	the objective response rate (orr) is defined as the proportion of participants who achieve either a complete remission (cr) or a partial remission (pr) as their best overall response during the systemic treatment phase. assessments will be conducted by the investigator in accordance with the lugano classification 2014 criteria for malignant lymphoma (or recil 2017 if applicable). this measure evaluates the combined efficacy of the induction and consolidation regimens (sca and/or p-gemox) in reducing tumor burden prior to the administration of local radiotherapy.; complete remission (cr): disappearance of all target lesions, normalization of lymph nodes, and metabolic complete response (deauville score 1-3).; partial remission (pr): ≥50% decrease in the sum of the products of the perpendicular diameters of target lesions, taking into account the appearance of new lesions or flares in fdg-avid disease.	From Baseline to the End of Systemic Treatment or the completion of 6 cycles (each cycle is 21 days), whichever occurs first.
Partial Remission (PR) rate	The Partial Remission (PR) rate is defined as the proportion of participants who achieve a Partial Remission (PR) as their best overall response during the study treatment period. Tumor response will be assessed by the Investigator according to the Lugano Classification 2014 criteria (or RECIL 2017 if applicable). This endpoint measures the efficacy of the SCA induction regimen and subsequent response-adapted therapy (SCA consolidation or P-GemOx chemotherapy) in reducing the tumor burden in patients with previously untreated ENKTL. A PR is defined as a ≥50% decrease in the sum of the products of the perpendicular diameters of target lesions, taking into account the appearance of new lesions or flares in FDG-avid disease.	From Baseline to the End of Systemic Treatment or the completion of 6 cycles (each cycle is 21 days), whichever occurs first.
Progression-Free Survival	The Progression-Free Survival (PFS) is defined as the time from the date of initial treatment (first dose of the SCA regimen) to the date of disease progression or death from any cause, whichever occurs first. Disease progression will be determined by the Investigator based on radiological imaging (CT/MRI) and clinical assessment according to the Lugano Classification 2014 criteria (or RECIL 2017). Patients who do not experience the event (progression or death) at the time of data cutoff will be censored at the date of their last adequate disease assessment. Patients who initiate new anti-cancer therapy without documented progression will also be censored at the start date of the new therapy.	From date of initial treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months.
Duration of Response	The Duration of Response (DoR) is defined as the time from the date of first documented response (either Complete Remission or Partial Remission) to the date of disease progression or death from any cause, whichever occurs first. Disease progression will be determined by the Investigator based on radiological imaging and clinical assessment according to the Lugano Classification 2014 criteria (or RECIL 2017). Only participants who achieve a CR or PR are evaluable for this endpoint. Patients who do not experience the event (progression or death) at the time of data cutoff will be censored at the date of their last adequate disease assessment.	From date of first documented response until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months.
Overall Survival	The Overall Survival (OS) is defined as the time from the date of initial treatment (first dose of the SCA regimen) to the date of death from any cause. Patients who are alive at the time of the data cutoff or who are lost to follow-up will be censored at the date of their last known contact. This endpoint serves as a key measure of the long-term efficacy and clinical benefit of the sequential SCA and P-GemOx regimen combined with radiotherapy in the treatment of previously untreated ENKTL.	From date of initial treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.
Adverse Events	The incidence and severity of Adverse Events (AEs) will be monitored and recorded throughout the study. This includes all untoward medical occurrences, laboratory abnormalities (hematology and chemistry), and serious adverse events (SAEs). The severity of each AE will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. The assessment will focus on the safety and tolerability of the SCA induction regimen (Sintilimab, Chidamide, and Azacitidine), the response-adapted consolidation therapy (SCA or P-GemOx), and the subsequent involved-field radiotherapy.	From the date of informed consent and first dose of study drug up to 30 days (or 90 days for immune-related AEs) after the last dose of study treatment or completion of radiotherapy.

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: April 3, 2026
• First Submitted That Met QC Criteria: April 17, 2026
• First Posted (Actual): April 21, 2026

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Azacitidine; Sintilimab; Chidamide; First-line Therapy; Extranodal NK/T-cell Lymphoma
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Lymphoma, Extranodal NK-T-Cell
• Other Study ID Numbers: SCENT-3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No