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)
Overview
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Sponsor
- Sun Yat-sen University
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Complete Remission rate
Overview
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).
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
- •At least one evaluable or measurable lesion
- •Ann Arbor stage I-II disease.
- •PINK-E score ≥
- •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
- •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.
Arms & Interventions
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).
Intervention: SCA Induction followed by Response-Adapted Therapy (Drug)
Outcomes
Primary Outcomes
Complete Remission rate
Time Frame: 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.
Secondary Outcomes
- 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.)
- Adverse Events(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.)
Investigators
Huiqiang Huang
Professor
Sun Yat-sen University