A Study Comparing of P-GEMD Regimen Versus P-Gemox Regimen With Untreated Early-Stage NUAT or Advanced-Stage ENKTL.

A Multicenter, Randomized Controlled Clinical Study of Pegaspargase Combined With P-GEMD Regimen Versus P-Gemox Regimen in the Treatment of Untreated Early-Stage Non-Upper Aerodigestive Tract or Advanced-Stage Extranodal NK/T-Cell Lymphoma.

Extranodal natural-killer (NK)/T-cell lymphoma (ENKTL) is an aggressive subtype of non-Hodgkin lymphoma with a poor prognosis. Notably, patients with advanced-stage disease or early-stage non-upper aero-digestive tract (NUAT) involvement frequently develop hemophagocytic lymphohistiocytosis (HLH), necessitating more effective therapeutic interventions. This Multicenter, Randomized Controlled Clinical Study aimed to compare the efficacy and safety of P-GEMD and P-Gemox in the treatment of newly diagnosed early NUAT or advanced-stage ENKTL.

Study Overview

• Status: Not yet recruiting
• Conditions: NK-T-Cell Lymphoma, Extranodal
• Intervention / Treatment: Drug: P-GEMD; Drug: P-Gemox

Detailed Description

This Multicenter, Randomized Controlled Clinical Study aimed to compare the efficacy and safety of P-GEMD and P-Gemox in the treatment of newly diagnosed early NUAT or advanced-stage ENKTL. The P-GEMD regimen (pegaspargase; gemcitabine; etoposide; mitoxantrone hydrochlorid liposome; dexamethasone) was administered intravenously every 3 weeks until up to 6 cycles of planned therapy. The P-Gemox regimen ( Pegaspargase, Gemcitabine, and Oxaliplatin) was administered intravenously 3 weeks until up to 6 cycles of planned therapy.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jinhua Liang; Email: 1151525490@qq.com
• Study Contact Backup: Name: Wei Xu; Phone Number: 8613951699449; Email: xuwei10000@hotmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1. Voluntarily join this study and sign the informed consent form; 2.Age ≥18 years old; 3.Expected survival time ≥ 3 months; 4. Histopathologically confirmed early non-upper aerodigestive or advanced ENKTL; 5. There must be at least one evaluable or measurable lesion that meets the Lugano2014 criteria: lymph node lesions, measurable lymph nodes need to have a long diameter > 1.5cm; non-lymph node lesions, extranodal lesions that can be measured Long diameter > 1.0cm; 6. ECOG score 0-2 points; 7. Bone marrow function: neutrophil count ≥ 1.5×109/L, platelet count ≥ 75×109/L, hemoglobin ≥ 80g/L(Restriction may be relaxed in patients with bone marrow involvement, Absolute neutrophil count (ANC) ≥1.0×109/L, Platelet count (PLT) ≥50×109/L, Hemoglobin(HB)≥ 75g/L); 8. Liver and kidney function: serum creatinine ≤ 1.5 times the upper limit of the normal value; alanine aminotransferase (AST) and aspartate aminotransferase (ALT) ≤ 2.5 times the upper limit of the normal value (for patients with liver invasion ≤ 5 times the normal value upper limit); total bilirubin ≤ 1.5 times the upper limit of normal value (for patients with liver invasion ≤ 3 times the upper limit of normal value).

Exclusion Criteria:

• 1.Hypersensitivity to any study drug or its components; 2. Uncontrollable systemic diseases (such as advanced infection, uncontrollable hypertension, diabetes, etc.); 3. Cardiac function and disease meet one of the following conditions : A.long QTc syndrome or QTc interval >480 ms; B.complete left bundle branch block, second-degree or third-degree atrioventricular block; C.severe, uncontrolled arrhythmia requiring drug treatment ; D.New York Society of Cardiology ≥ Grade III; E.Cardiac ejection fraction (LVEF) lower than 50%; F.Myocardial infarction, unstable angina, and severely unstable ventricular rhythm within 6 months before recruitment History of arrhythmia or any other arrhythmia requiring treatment, history of clinically severe pericardial disease, or ECG evidence of acute ischemia or active conduction system abnormalities.

  4. Active hepatitis B and C infection (positive hepatitis B virus surface antigen and more than 1x103 copies/mL of hepatitis B virus DNA; more than 1x103 copies/mL of hepatitis C virus RNA); 5. Human immunodeficiency virus (HIV) infection (positive HIV antibody); 6. Previously or currently suffering from other malignant tumors (except for effectively controlled non-melanoma skin basal cell carcinoma, breast/cervix carcinoma in situ and other malignant tumors that have been effectively controlled without treatment in the past five years); 7. Central nervous system (CNS) involvement at the time of recruitment; 8. Pregnant, lactating women and patients of childbearing age who do not want to take contraceptive measures; 9.Other investigators judge that they are not suitable for participating in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: P-GEMD; The P-GEMD regimen (pegaspargase at 3750 IU, d2; gemcitabine at 1000 mg/m2, d1; etoposide at 65 mg/m2, d2-4; mitoxantrone hydrochloride liposome at 12mg/m2, d1; dexamethasone at 40 mg/d, d1-4.) was administered intravenously every 3 weeks until up to 6 cycles of planned therapy.	Drug: P-GEMD; Drug: Mitoxantrone hydrochloride liposome Mitoxantrone hydrochloride liposome (12 mg/m2) on day 1, every 3 weeks; Drug: Pegaspargase Pegaspargase(3750 IU) on day 2, every 3 weeks; Drug: Gemcitabine Gemcitabine (1000 mg/m2) on day 1, every 3 weeks; Drug: Etoposide Etoposide (65 mg/m2) on day 2-4, every 3 weeks. Drug: Dexamethasone Dexamethasone (40 mg/d) will be taken orally from day 1-4, every 3 weeks; Patients > 65 years of age may be adjusted according to the investigator's decision.
Other: P-Gemox; The P-Gemox regimen (pegaspargase at 2000-2500 IU/m2, d2; gemcitabine at 1000 mg/m2, d1, d8; oxaliplatin at 130 mg/m2, d1) was administered intravenously every 3 weeks until up to 6 cycles of planned therapy.	Drug: P-Gemox; Drug: Pegaspargase Pegaspargase(2000-2500 IU/m2) on day 1, every 3 weeks; Drug: Gemcitabine Gemcitabine (1000 mg/m2) on day 1 and day 8, every 3 weeks; Drug: Oxaliplatin Oxaliplatin (130mg/m2) on day 1, every 3 weeks; Patients > 65 years of age may be adjusted according to the investigator's decision.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response (CR) Rate	Response is assessed according to the lugano criteria.	5.5years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	Response is assessed according to the lugano criteria.	5.5years
Progression-Free-Survival (PFS)	From the time subjects were enrolled to the time of disease progression (in any way) or death from any cause.	5.5years
Duration of Response (DOR)	The time between meeting the criteria for treatment effectiveness (first recorded complete or partial response) and the first clear recurrence or progression.	5.5years
Overall survival (OS)	From the date of inclusion to date of death, irrespective of cause.	5.5years
EBV-DNA load level (before and after treatment)	EBV-DNA was detected at time points before and after treatment.	5.5 years
Hematologic and non-hematologic toxicity.	The safety of the drug was evaluated by NCI-CTC AE 5.0 standard.Hematologic and non-hematologic toxicity.	From the first day of medication to 28 days after the last dose

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University
• Investigators: Principal Investigator: Wei Xu, he First Affiliated Hospital with Nanjing Medical University, Nanjing, China; Principal Investigator: Jinhua Liang, he First Affiliated Hospital with Nanjing Medical University, Nanjing, China

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: April 24, 2025
• First Submitted That Met QC Criteria: April 24, 2025
• First Posted (Actual): May 1, 2025

Study Record Updates

• Last Update Posted (Actual): May 1, 2025
• Last Update Submitted That Met QC Criteria: April 24, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, Extranodal NK-T-Cell
• Other Study ID Numbers: CSPC-DED-NKTCL-K05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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