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

NCT07542912 | Not Yet Recruiting

• 1 other identifier: SCENT-3
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Complete Remission Rate， CRR; Progression Free Survival; Overall Survival; Adverse Event; Duration of Response

Keywords

Extranodal NK/T-cell Lymphoma; First-line Therapy; Sintilimab; Chidamide; Azacitidine

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• objective response rate

  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

  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

  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

  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

  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.

Study Arms (1)

Experimental: SCA Induction followed by Response-Adapted Therapy

EXPERIMENTAL

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

Interventions

SCA Induction followed by Response-Adapted Therapy DRUG

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).

Experimental: SCA Induction followed by Response-Adapted Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, China

Location

MeSH Terms

Conditions

Lymphoma, Extranodal NK-T-Cell

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms

Central Study Contacts

Huiqiang Huang, Ph.D.

CONTACT

020-87343009; huanghq@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 3, 2026
• First Posted: April 21, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2029
• Last Updated: April 21, 2026

Record last verified: 2026-04

Locations

CN (1)