Natural Killer/T-cell LymphomaPhase 2NCT07768943
GELAD-Based Response-Adapted Treatment for Early-Stage Extranodal NK/T-Cell Lymphoma
A Phase 2 study testing Gemcitabine (GEM), Etoposide Injection and Dexamethasone in people with Natural Killer/T-cell Lymphoma, run by Fudan University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Natural Killer/T-cell Lymphoma
- What is being tested?
- Gemcitabine (GEM), Etoposide Injection and Dexamethasone
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 620 participants
- Where
- 1 siteChina
- Study dates
- 1 Sep 2026to 30 Jun 2036
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 to 75 years, inclusive.
- Histologically confirmed extranodal NK/T-cell lymphoma, nasal type, according to the 2022 World Health Organization classification.
- Diagnosis confirmed by institutional or central pathological review. Tumor tissue must be adequate for morphological assessment, immunohistochemistry, and Epstein-Barr virus-encoded RNA in situ hybridization.
- Lugano 2014 stage IE or IIE disease with a primary site in the upper aerodigestive tract, including but not limited to the nasal cavity, paranasal sinuses, nasopharynx, oropharynx, or oral cavity.
- At least one disease lesion evaluable by PET/CT at baseline.
- No previous chemotherapy, radiotherapy, immunotherapy, or other antitumor biological therapy for lymphoma.
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- Eastern Cooperative Oncology Group performance status of 0 to 2.
- Adequate organ function, including:
- Absolute neutrophil count at least 1.0 x 10^9/L.
- Platelet count at least 75 x 10^9/L.
- Hemoglobin at least 90 g/L.
- No granulocyte colony-stimulating factor, platelet transfusion, or red blood cell transfusion within 14 days before enrollment.
- Total bilirubin no greater than 1.5 times the upper limit of normal.
- Alanine aminotransferase and aspartate aminotransferase no greater than 2 times the upper limit of normal.
- Serum creatinine no greater than 1.5 times the upper limit of normal.
- Fibrinogen at least 1.5 g/L.
- Left ventricular ejection fraction at least 50%.
- Ability to understand the study and provide written informed consent.
- Willingness to comply with protocol treatment, follow-up, laboratory testing, imaging assessments, and biospecimen collection.
Who cannot join
- Diagnosis not meeting the 2022 World Health Organization criteria for extranodal NK/T-cell lymphoma or not confirmed after pathological review.
- Lugano stage III or IV disease or distant organ involvement inconsistent with localized early-stage disease.
- Primary disease outside the upper aerodigestive tract or predominantly systemic or widespread extranodal disease.
- Previous lymphoma-directed chemotherapy, radiotherapy, immunotherapy, or other systemic antitumor treatment.
- Human immunodeficiency virus infection, active hepatitis C virus infection, or hepatitis B virus infection with HBV DNA greater than 10^3/mL.
- History of pancreatitis or pancreatic disease considered unsuitable for pegaspargase treatment.
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- Acute or systemic infection requiring intravenous anti-infective treatment.
- Severe complications including hemophagocytic lymphohistiocytosis or disseminated intravascular coagulation.
- Significant organ dysfunction, including respiratory failure, chronic congestive heart failure of New York Heart Association class II or higher, decompensated hepatic or renal dysfunction, uncontrolled hypertension or diabetes despite appropriate treatment, or cardiovascular or cerebrovascular thrombosis or bleeding within the previous 6 months.
- Active autoimmune disease or another condition considered by the investigator to make immune checkpoint inhibitor treatment unsuitable.
- Pregnancy or breastfeeding.
- Participants of reproductive potential who are unwilling to use adequate contraception.
- Known severe hypersensitivity to any study drug or its excipients.
- Another active malignancy within the previous 6 months requiring surgery, radiotherapy, or systemic anticancer therapy.
- Severe psychiatric disorder, poor adherence, or another condition that, in the investigator's judgment, would prevent completion of protocol treatment or follow-up.
- Current use of another investigational drug or participation in another interventional clinical trial within 4 weeks before enrollment.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, 200032
Rong Tao, MD, 008621-64175590 ext. 660103, hkutao@gmail.com
Chuanxu Liu, MD, 008621-64175590 ext. 660103, liuchaunxu@shca.or.cn
About this study
Official title: A Prospective Multicenter Response-Adapted Treatment Study Based on Early Response Assessment After GELAD Induction Chemotherapy in Early-Stage Extranodal NK/T-Cell Lymphoma
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.
Read more
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.
Read the detailed description
This is an investigator-initiated, prospective, multicenter, response-adapted master protocol for previously untreated patients with stage IE or IIE extranodal NK/T-cell lymphoma of the upper aerodigestive tract.
All enrolled participants first receive two 21-day cycles of GELAD induction chemotherapy consisting of gemcitabine, etoposide, pegaspargase, and dexamethasone. Early response assessment is performed 14 to 21 days after completion of the second GELAD cycle and includes whole-body PET/CT, quantitative plasma EBV DNA, contrast-enhanced MRI or CT of the primary site, and nasal endoscopy.
Participants are subsequently assigned to one of three response-defined modules.
PART A includes participants who achieve complete metabolic response on PET/CT and have negative plasma EBV DNA. These participants are randomized centrally in a 1:1 ratio, stratified by NRI 0-1 versus NRI 2 or higher, to receive either 50 Gy in 25 fractions (A0, standard-dose radiotherapy) or 40 Gy in 20 fractions (A1, reduced-dose radiotherapy). Both groups subsequently receive two additional cycles of GELAD. PART A is designed as a noninferiority comparison. The primary endpoint is the 24-month progression-free survival rate from randomization. The prespecified noninferiority margin for the absolute difference in PFS24 between A1 and A0 is -10 percentage points. A total of 280 participants are planned for randomization in PART A.
PART B includes participants with partial response on PET/CT and negative plasma EBV DNA. These participants are not randomized and receive 50 Gy in 25 fractions followed by two additional cycles of GELAD. PART B serves as a prospective standard-treatment platform cohort and has no formal primary hypothesis test.
PART C includes participants with stable disease, local or regional progressive disease that remains within a field amenable to curative radiotherapy, or partial response with persistent positive plasma EBV DNA after two cycles of GELAD. Participants with distant progression or progression to stage III or IV disease are considered to have induction failure and do not enter PART C. Participants in PART C receive 50 Gy in 25 fractions followed by sintilimab 200 mg intravenously every 3 weeks. Sintilimab is administered for at least 24 weeks. Treatment 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 duration of sintilimab is 24 months or 35 cycles. PART C is a single-arm phase 2 module. Its primary endpoint is the 24-month progression-free survival rate from PART C module registration, evaluated against a prespecified null benchmark of 55%.
Approximately 620 participants are expected to be registered in the master protocol. Enrollment may be increased, based only on a blinded feasibility review of actual module-assignment proportions, to a maximum of 660 participants. Participants are followed every 3 months during the first 2 years after completion or discontinuation of protocol treatment, every 6 months during years 3 through 5, and annually thereafter.
- Conditions
- Natural Killer/T-cell Lymphoma
- Being tested
- Gemcitabine (GEM), Etoposide Injection, Dexamethasone, pegaspargase, IMRT 50 Gy
- Keywords
- Extranodal NK/T-cell lymphoma, Early-stage NK/T-cell lymphoma, GELAD, Response-adapted therapy, Radiotherapy de-escalation, Sintilimab, PD-1 blockade, PET/CT, Epstein-Barr virus DNA
- Medical subject headings
- Lymphoma, Extranodal NK-T-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gemcitabine (GEM)Drug
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.
Etoposide InjectionDrug
Etoposide 60 mg/m^2 is administered intravenously on Days 1 through 3 of each 21-day GELAD cycle.
DexamethasoneDrug
Dexamethasone 20 mg per day is administered intravenously on Days 1 through 4 of each 21-day GELAD cycle.
pegaspargaseDrug
Pegaspargase 2000 U/m^2, capped at 3750 U per dose, is administered intramuscularly on Day 1 of each 21-day GELAD cycle.
IMRT 50 GyRadiation
Intensity-modulated radiotherapy is delivered at a total dose of 50 Gy in 25 fractions, 2.0 Gy per fraction, 5 fractions per week.
IMRT 40 GyRadiation
Intensity-modulated radiotherapy is delivered at a total dose of 40 Gy in 20 fractions, 2.0 Gy per fraction, 5 fractions per week.
SintilimabDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| PART A A0: Standard-Dose Radiotherapy | Active comparator | Participants who achieve complete metabolic response on PET/CT and negative plasma EBV DNA after two cycles of GELAD are randomized to standard-dose intensity-modulated radiotherapy (IMRT), 50 Gy in 25 fractions, followed by two additional 21-day cycles of GELAD. Receives: Drug: Gemcitabine (GEM); Drug: Etoposide Injection; Drug: Dexamethasone; Drug: pegaspargase; Radiation: IMRT 50 Gy |
| PART A A1: Reduced-Dose Radiotherapy | Experimental | Participants who achieve complete metabolic response on PET/CT and negative plasma EBV DNA after two cycles of GELAD are randomized to reduced-dose IMRT, 40 Gy in 20 fractions, followed by two additional 21-day cycles of GELAD. Receives: Drug: Gemcitabine (GEM); Drug: Etoposide Injection; Drug: Dexamethasone; Drug: pegaspargase; Radiation: IMRT 40 Gy |
| PART B: Standard Treatment Platform | Other | Participants with partial response on PET/CT and negative plasma EBV DNA after two cycles of GELAD receive IMRT, 50 Gy in 25 fractions, followed by two additional 21-day cycles of GELAD. Receives: Drug: Gemcitabine (GEM); Drug: Etoposide Injection; Drug: Dexamethasone; Drug: pegaspargase; Radiation: IMRT 50 Gy |
| PART C: Sintilimab Consolidation | Experimental | Participants with stable disease, local or regional progressive disease that remains amenable to curative radiotherapy, or partial response with positive plasma EBV DNA after two cycles of GELAD receive IMRT, 50 Gy in 25 fractions, followed by sintilimab 200 mg intravenously every 3 weeks. Sintilimab is administered for at least 24 weeks and is discontinued after complete metabolic response and EBV DNA negativity have both been sustained for at least 24 weeks. The maximum duration is 24 months or 35 cycles. Receives: Drug: Gemcitabine (GEM); Drug: Etoposide Injection; Drug: Dexamethasone; Drug: pegaspargase; Radiation: IMRT 50 Gy; Drug: Sintilimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
24-Month Progression-Free Survival Rate in PART A
Progression-free survival (PFS) is measured from the date of PART A randomization to the first documented disease progression, relapse, or death from any cause, whichever occurs first. Participants without a PFS event are censored at the date of the last adequate disease assessment. The 24-month PFS rate will be estimated using the Kaplan-Meier method. The primary treatment effect is the absolute difference in PFS24 between A1 (40 Gy) and A0 (50 Gy), calculated as A1 minus A0. Noninferiority is concluded if the lower bound of the two-sided 95% confidence interval for this difference is greater than -10 percentage points.
Measured: From PART A randomization through 24 months
24-Month Progression-Free Survival Rate in PART C
Progression-free survival (PFS) is measured from the date of PART C module registration, which occurs before radiotherapy, to the first documented disease progression, relapse, or death from any cause, whichever occurs first. Participants without a PFS event are censored at the date of the last adequate disease assessment. The 24-month PFS rate will be estimated using the Kaplan-Meier method and evaluated against the prespecified null benchmark of 55%.
Measured: From PART C module registration through 24 months
Secondary outcomes (7)
Percentage of Participants With Complete Response at the End of Treatment
Complete response is assessed according to the Lugano 2014 response criteria. Participants who are not evaluable at the protocol-defined end-of-treatment assessment are considered not to have achieved complete response in the primary analysis.
Measured: At the protocol-defined end-of-treatment assessment, approximately 6 weeks plus or minus 2 weeks after the final protocol treatment
Percentage of Participants With an Overall Response at the End of Treatment
Overall response is defined as complete response or partial response according to the Lugano 2014 response criteria.
Measured: At the protocol-defined end-of-treatment assessment, approximately 6 weeks plus or minus 2 weeks after the final protocol treatment
Overall Survival
Overall survival is defined as the time from the first GELAD dose to death from any cause. Participants who are alive are censored at the date they were last known to be alive.
Measured: From the first GELAD dose through 60 months
Locoregional Control Rate at 12, 24, and 36 Months
Description: Locoregional failure is defined as recurrence or progression within the primary radiotherapy region, involved cervical nodal region, or adjacent locoregional region. Locoregional control rates will be estimated at prespecified time points.
Measured: At 12, 24, and 36 months after module assignment
Percentage of Baseline EBV DNA-Positive Participants Achieving Confirmed Plasma EBV DNA Clearance
Plasma EBV DNA below 500 copies/mL is defined as negative. Confirmed clearance is defined as conversion from positive to negative plasma EBV DNA with at least two consecutive negative measurements separated by at least 2 weeks.
Measured: From the first GELAD dose through 24 months
Number of Participants With Adverse Events as Assessed by CTCAE Version 5.0
Adverse events, serious adverse events, grade 3 or higher adverse events, treatment-related adverse events, treatment discontinuations due to toxicity, and treatment-related deaths will be collected. Radiation-related acute and late toxicities and immune-related adverse events in PART C will be specifically evaluated.
Measured: From the first study treatment through the protocol-defined safety follow-up after the final study treatment, up to approximately 26 months
Percentage of PART C Participants in Treatment-Free Remission at 24 Months
Treatment-free remission at 24 months is defined as being alive and progression-free at 24 months after PART C module registration, having discontinued sintilimab for at least 6 months, and having received no additional anticancer therapy after discontinuation.
Measured: 24 months after PART C module registration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2026
- Study start1 Sep 2026 (estimated)
- Primary completion30 Jun 2033 (estimated)
- Study completion30 Jun 2036 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Natural Killer/T-cell LymphomaStudies of the same condition, open and under way.
- More trials run by Fudan UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- This response-adapted master protocol includes a common induction period followed by response-defined treatment assignment. All participants initially receive two cycles of GELAD. After early PET/CT and plasma EBV DNA assessment, participants enter PART A, PART B, or PART C according to prespecified response criteria. Only PART A includes randomized allocation: participants with complete metabolic response and negative EBV DNA are randomized 1:1 to 50 Gy versus 40 Gy radiotherapy, with identical post-radiotherapy GELAD treatment. PART B and PART C are nonrandomized response-defined modules.
- Masking
- None (open label)
- Enrolment
- 620 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rong Tao, Fudan University
- Investigators
- Rong Tao, MD, Study chair, Fudan UniversityChuanxu Liu, MD, Principal investigator, Fudan UniversityXuejun Ma, MD, Principal investigator, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07768943
- Sponsor's protocol ID
- SHCA-NKTCL-RA26
- Status last verified
- Aug 2026
- First submitted
- 12 Aug 2026
- Last updated
- 17 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: De-identified individual participant data underlying the published study results may be made available to qualified researchers following submission and approval of a scientifically justified research proposal and execution of an appropriate data-use agreement.
Publications
Tao R, Fan L, Song Y, Hu Y, Zhang W, Wang Y, Xu W, Li J. Sintilimab for relapsed/refractory extranodal NK/T cell lymphoma: a multicenter, single-arm, phase 2 trial (ORIENT-4). Signal Transduct Target Ther. 2021 Oct 27;6(1):365. doi: 10.1038/s41392-021-00768-0.
PubMed 34702811Zhu Y, Tian S, Xu L, Ma Y, Zhang W, Wang L, Jin L, Liu C, Zhu C, Li Z, Hao S, Zhong H, Ding H, Tao R. GELAD chemotherapy with sandwiched radiotherapy for patients with newly diagnosed stage IE/IIE natural killer/T-cell lymphoma: a prospective multicentre study. Br J Haematol. 2022 Feb;196(4):939-946. doi: 10.1111/bjh.17960. Epub 2021 Nov 21.
PubMed 34806163
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Multicenter Response-Adapted Treatment Study Based on Early Response Assessment After GELAD Induction Chemotherapy in Early-Stage Extranodal NK/T-Cell Lymphoma
- ClinicalTrials.gov ID
- NCT07768943
- Acronym / sponsor ID
- SHCA-NKTCL-RA26
- Conditions
- Natural Killer/T-cell Lymphoma
- Keywords
- Extranodal NK/T-cell lymphoma, Early-stage NK/T-cell lymphoma, GELAD, Response-adapted therapy, Radiotherapy de-escalation, Sintilimab, PD-1 blockade, PET/CT
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 620 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- 1 Sep 2026 (estimated)
- Primary completion
- 30 Jun 2033 (estimated)
- Study completion
- 30 Jun 2036 (estimated)
- First posted
- 17 Aug 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is an investigator-initiated, prospective, multicenter, response-adapted master protocol for previously untreated patients with stage IE or IIE extranodal NK/T-cell lymphoma of the upper aerodigestive tract.
All enrolled participants first receive two 21-day cycles of GELAD induction chemotherapy consisting of gemcitabine, etoposide, pegaspargase, and dexamethasone. Early response assessment is performed 14 to 21 days after completion of the second GELAD cycle and includes whole-body PET/CT, quantitative plasma EBV DNA, contrast-enhanced MRI or CT of the primary site, and nasal endoscopy.
Participants are subsequently assigned to one of three response-defined modules.
PART A includes participants who achieve complete metabolic response on PET/CT and have negative plasma EBV DNA. These participants are randomized centrally in a 1:1 ratio, stratified by NRI 0-1 versus NRI 2 or higher, to receive either 50 Gy in 25 fractions (A0, standard-dose radiotherapy) or 40 Gy in 20 fractions (A1, reduced-dose radiotherapy). Both groups subsequently receive two additional cycles of GELAD. PART A is designed as a noninferiority comparison. The primary endpoint is the 24-month progression-free survival rate from randomization. The prespecified noninferiority margin for the absolute difference in PFS24 between A1 and A0 is -10 percentage points. A total of 280 participants are planned for randomization in PART A.
PART B includes participants with partial response on PET/CT and negative plasma EBV DNA. These participants are not randomized and receive 50 Gy in 25 fractions followed by two additional cycles of GELAD. PART B serves as a prospective standard-treatment platform cohort and has no formal primary hypothesis test.
PART C includes participants with stable disease, local or regional progressive disease that remains within a field amenable to curative radiotherapy, or partial response with persistent positive plasma EBV DNA after two cycles of GELAD. Participants with distant progression or progression to stage III or IV disease are considered to have induction failure and do not enter PART C. Participants in PART C receive 50 Gy in 25 fractions followed by sintilimab 200 mg intravenously every 3 weeks. Sintilimab is administered for at least 24 weeks. Treatment 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 duration of sintilimab is 24 months or 35 cycles. PART C is a single-arm phase 2 module. Its primary endpoint is the 24-month progression-free survival rate from PART C module registration, evaluated against a prespecified null benchmark of 55%.
Approximately 620 participants are expected to be registered in the master protocol. Enrollment may be increased, based only on a blinded feasibility review of actual module-assignment proportions, to a maximum of 660 participants. Participants are followed every 3 months during the first 2 years after completion or discontinuation of protocol treatment, every 6 months during years 3 through 5, and annually thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- This response-adapted master protocol includes a common induction period followed by response-defined treatment assignment. All participants initially receive two cycles of GELAD. After early PET/CT and plasma EBV DNA assessment, participants enter PART A, PART B, or PART C according to prespecified response criteria. Only PART A includes randomized allocation: participants with complete metabolic response and negative EBV DNA are randomized 1:1 to 50 Gy versus 40 Gy radiotherapy, with identical post-radiotherapy GELAD treatment. PART B and PART C are nonrandomized response-defined modules.
| Arm | Type | Receives |
|---|---|---|
| PART A A0: Standard-Dose Radiotherapy | Active comparator | Drug: Gemcitabine (GEM), Drug: Etoposide Injection, Drug: Dexamethasone, Drug: pegaspargase, Radiation: IMRT 50 GyParticipants who achieve complete metabolic response on PET/CT and negative plasma EBV DNA after two cycles of GELAD are randomized to standard-dose intensity-modulated radiotherapy (IMRT), 50 Gy in 25 fractions, followed by two additional 21-day cycles of GELAD. |
| PART A A1: Reduced-Dose Radiotherapy | Experimental | Drug: Gemcitabine (GEM), Drug: Etoposide Injection, Drug: Dexamethasone, Drug: pegaspargase, Radiation: IMRT 40 GyParticipants who achieve complete metabolic response on PET/CT and negative plasma EBV DNA after two cycles of GELAD are randomized to reduced-dose IMRT, 40 Gy in 20 fractions, followed by two additional 21-day cycles of GELAD. |
| PART B: Standard Treatment Platform | Other | Drug: Gemcitabine (GEM), Drug: Etoposide Injection, Drug: Dexamethasone, Drug: pegaspargase, Radiation: IMRT 50 GyParticipants with partial response on PET/CT and negative plasma EBV DNA after two cycles of GELAD receive IMRT, 50 Gy in 25 fractions, followed by two additional 21-day cycles of GELAD. |
| PART C: Sintilimab Consolidation | Experimental | Drug: Gemcitabine (GEM), Drug: Etoposide Injection, Drug: Dexamethasone, Drug: pegaspargase, Radiation: IMRT 50 Gy, Drug: SintilimabParticipants with stable disease, local or regional progressive disease that remains amenable to curative radiotherapy, or partial response with positive plasma EBV DNA after two cycles of GELAD receive IMRT, 50 Gy in 25 fractions, followed by sintilimab 200 mg intravenously every 3 weeks. Sintilimab is administered for at least 24 weeks and is discontinued after complete metabolic response and EBV DNA negativity have both been sustained for at least 24 weeks. The maximum duration is 24 months or 35 cycles. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Age 18 to 75 years, inclusive.
- Histologically confirmed extranodal NK/T-cell lymphoma, nasal type, according to the 2022 World Health Organization classification.
- Diagnosis confirmed by institutional or central pathological review. Tumor tissue must be adequate for morphological assessment, immunohistochemistry, and Epstein-Barr virus-encoded RNA in situ hybridization.
- Lugano 2014 stage IE or IIE disease with a primary site in the upper aerodigestive tract, including but not limited to the nasal cavity, paranasal sinuses, nasopharynx, oropharynx, or oral cavity.
- At least one disease lesion evaluable by PET/CT at baseline.
Key exclusion criteria (16 listed)
- Diagnosis not meeting the 2022 World Health Organization criteria for extranodal NK/T-cell lymphoma or not confirmed after pathological review.
- Lugano stage III or IV disease or distant organ involvement inconsistent with localized early-stage disease.
- Primary disease outside the upper aerodigestive tract or predominantly systemic or widespread extranodal disease.
- Previous lymphoma-directed chemotherapy, radiotherapy, immunotherapy, or other systemic antitumor treatment.
- Human immunodeficiency virus infection, active hepatitis C virus infection, or hepatitis B virus infection with HBV DNA greater than 10^3/mL.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | PART A A0: Standard-Dose Radiotherapy, PART A A1: Reduced-Dose Radiotherapy, PART B: Standard Treatment Platform, PART C: Sintilimab Consolidation |
| Etoposide InjectionEtoposide 60 mg/m^2 is administered intravenously on Days 1 through 3 of each 21-day GELAD cycle. | Drug | PART A A0: Standard-Dose Radiotherapy, PART A A1: Reduced-Dose Radiotherapy, PART B: Standard Treatment Platform, PART C: Sintilimab Consolidation |
| DexamethasoneDexamethasone 20 mg per day is administered intravenously on Days 1 through 4 of each 21-day GELAD cycle. | Drug | PART A A0: Standard-Dose Radiotherapy, PART A A1: Reduced-Dose Radiotherapy, PART B: Standard Treatment Platform, PART C: Sintilimab Consolidation |
| pegaspargasePegaspargase 2000 U/m^2, capped at 3750 U per dose, is administered intramuscularly on Day 1 of each 21-day GELAD cycle. | Drug | PART A A0: Standard-Dose Radiotherapy, PART A A1: Reduced-Dose Radiotherapy, PART B: Standard Treatment Platform, PART C: Sintilimab Consolidation |
| IMRT 50 GyIntensity-modulated radiotherapy is delivered at a total dose of 50 Gy in 25 fractions, 2.0 Gy per fraction, 5 fractions per week. | Radiation | PART A A0: Standard-Dose Radiotherapy, PART B: Standard Treatment Platform, PART C: Sintilimab Consolidation |
| IMRT 40 GyIntensity-modulated radiotherapy is delivered at a total dose of 40 Gy in 20 fractions, 2.0 Gy per fraction, 5 fractions per week. | Radiation | PART A A1: Reduced-Dose Radiotherapy |
| SintilimabSintilimab 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. | Drug | PART C: Sintilimab Consolidation |
Primary outcome
24-Month Progression-Free Survival Rate in PART A
Time frame: From PART A randomization through 24 months
Progression-free survival (PFS) is measured from the date of PART A randomization to the first documented disease progression, relapse, or death from any cause, whichever occurs first. Participants without a PFS event are censored at the date of the last adequate disease assessment. The 24-month PFS rate will be estimated using the Kaplan-Meier method. The primary treatment effect is the absolute difference in PFS24 between A1 (40 Gy) and A0 (50 Gy), calculated as A1 minus A0. Noninferiority is concluded if the lower bound of the two-sided 95% confidence interval for this difference is greater than -10 percentage points.
24-Month Progression-Free Survival Rate in PART C
Time frame: From PART C module registration through 24 months
Progression-free survival (PFS) is measured from the date of PART C module registration, which occurs before radiotherapy, to the first documented disease progression, relapse, or death from any cause, whichever occurs first. Participants without a PFS event are censored at the date of the last adequate disease assessment. The 24-month PFS rate will be estimated using the Kaplan-Meier method and evaluated against the prespecified null benchmark of 55%.
7 secondary outcomes
Percentage of Participants With Complete Response at the End of Treatment
Time frame: At the protocol-defined end-of-treatment assessment, approximately 6 weeks plus or minus 2 weeks after the final protocol treatment
Percentage of Participants With an Overall Response at the End of Treatment
Time frame: At the protocol-defined end-of-treatment assessment, approximately 6 weeks plus or minus 2 weeks after the final protocol treatment
Overall Survival
Time frame: From the first GELAD dose through 60 months
Locoregional Control Rate at 12, 24, and 36 Months
Time frame: At 12, 24, and 36 months after module assignment
Percentage of Baseline EBV DNA-Positive Participants Achieving Confirmed Plasma EBV DNA Clearance
Time frame: From the first GELAD dose through 24 months
Number of Participants With Adverse Events as Assessed by CTCAE Version 5.0
Time frame: From the first study treatment through the protocol-defined safety follow-up after the final study treatment, up to approximately 26 months
Percentage of PART C Participants in Treatment-Free Remission at 24 Months
Time frame: 24 months after PART C module registration
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2026.
- Results publication: PubMed 34702811Tao R, Fan L, Song Y, Hu Y, Zhang W, Wang Y, Xu W, Li J. Sintilimab for relapsed/refractory extranodal NK/T cell lymphoma: a multicenter, single-arm, phase 2 trial (ORIENT-4). Signal Transduct Target Ther. 2021 Oct 27;6(1):365. doi: 10.1038/s41392-021-00768-0.
- Results publication: PubMed 34806163Zhu Y, Tian S, Xu L, Ma Y, Zhang W, Wang L, Jin L, Liu C, Zhu C, Li Z, Hao S, Zhong H, Ding H, Tao R. GELAD chemotherapy with sandwiched radiotherapy for patients with newly diagnosed stage IE/IIE natural killer/T-cell lymphoma: a prospective multicentre study. Br J Haematol. 2022 Feb;196(4):939-946. doi: 10.1111/bjh.17960. Epub 2021 Nov 21.
- Individual participant dataSharing planned: Undecided. De-identified individual participant data underlying the published study results may be made available to qualified researchers following submission and approval of a scientifically justified research proposal and execution of an appropriate data-use agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Rong Tao, MD study chair
Fudan University
Chuanxu Liu, MD principal investigator
Fudan University
Xuejun Ma, MD principal investigator
Fudan University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Gemcitabine (GEM), Etoposide Injection and Dexamethasone in people with Natural Killer/T-cell Lymphoma, run by Fudan University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 17 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Rong Tao, MD (008621-64175590 ext. 660103, hkutao@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
24-Month Progression-Free Survival Rate in PART A (time frame: From PART A randomization through 24 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07768943, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2026.