GELAD-Based Response-Adapted Treatment for Early-Stage Extranodal NK/T-Cell Lymphoma

Summary

This prospective, multicenter study evaluates a response-adapted treatment strategy for previously untreated patients with early-stage extranodal NK/T-cell lymphoma of the upper aerodigestive tract.

All participants receive two cycles of GELAD induction chemotherapy, followed by early response assessment using positron emission tomography/computed tomography (PET/CT) and plasma Epstein-Barr virus (EBV) DNA. Subsequent treatment is determined by the early response.

Participants with complete metabolic response and negative EBV DNA enter PART A and are randomized 1:1 to standard-dose radiotherapy (50 Gy) or reduced-dose radiotherapy (40 Gy); both groups subsequently receive two additional cycles of GELAD. Participants with partial response and negative EBV DNA enter PART B and receive standard 50 Gy radiotherapy followed by two additional cycles of GELAD. Participants with stable disease, local or regional progressive disease that remains amenable to curative radiotherapy, or partial response with positive EBV DNA enter PART C and receive 50 Gy radiotherapy followed by response-adapted sintilimab consolidation.

The primary objective of PART A is to determine whether reduced-dose radiotherapy is noninferior to standard-dose radiotherapy with respect to the 24-month progression-free survival rate. The primary objective of PART C is to evaluate the 24-month progression-free survival rate with response-adapted sintilimab consolidation in patients with a high-risk early response.

Conditions

• Natural Killer/T-cell Lymphoma

Interventions

DRUG

Gemcitabine (GEM)

Gemcitabine 1.0 g/m\^2 is administered intravenously on Day 1 of each 21-day GELAD cycle. All participants receive two induction cycles. Participants in PART A A0, PART A A1, and PART B receive two additional GELAD cycles after radiotherapy.

DRUG

Etoposide Injection

Etoposide 60 mg/m\^2 is administered intravenously on Days 1 through 3 of each 21-day GELAD cycle.

DRUG

Dexamethasone

Dexamethasone 20 mg per day is administered intravenously on Days 1 through 4 of each 21-day GELAD cycle.

DRUG

pegaspargase

Pegaspargase 2000 U/m\^2, capped at 3750 U per dose, is administered intramuscularly on Day 1 of each 21-day GELAD cycle.

RADIATION

IMRT 50 Gy

Intensity-modulated radiotherapy is delivered at a total dose of 50 Gy in 25 fractions, 2.0 Gy per fraction, 5 fractions per week.

RADIATION

IMRT 40 Gy

Intensity-modulated radiotherapy is delivered at a total dose of 40 Gy in 20 fractions, 2.0 Gy per fraction, 5 fractions per week.

DRUG

Sintilimab

Sintilimab 200 mg is administered intravenously every 3 weeks after completion of radiotherapy in PART C. Treatment continues for at least 24 weeks. Sintilimab is discontinued when PET/CT complete metabolic response and plasma EBV DNA negativity have both been sustained for at least 24 weeks according to protocol-defined confirmation criteria. The maximum treatment duration is 24 months or 35 cycles.

Sponsors & Collaborators

• Fudan University

  lead OTHER

Principal Investigators

• Rong Tao, MD · Fudan University

• Chuanxu Liu, MD · Fudan University

• Xuejun Ma, MD · Fudan University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-09-01

Primary Completion

2033-06-30

Completion

2036-06-30

Countries

• China

Study Locations