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

Official title

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.

Overview

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.

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.

Interventions

• 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.
• 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.

Primary outcome measures

• Complete Response (CR) Rate [Time frame: 5.5years]

Secondary outcome measures (6)

• Overall Response Rate (ORR) [Time frame: 5.5years]
• Progression-Free-Survival (PFS) [Time frame: 5.5years]
• Duration of Response (DOR) [Time frame: 5.5years]
• Overall survival (OS) [Time frame: 5.5years]
• EBV-DNA load level (before and after treatment) [Time frame: 5.5 years]
• Hematologic and non-hematologic toxicity. [Time frame: From the first day of medication to 28 days after the last dose]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06953739 · CSPC-DED-NKTCL-K05

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗