Extranodal NK/T-cell LymphomaPhase 3BRIDGE-NKNCT07678229
BRIDGE-NK: Immunotherapy Versus Chemotherapy Induction Followed by Autologous HSCT in Advanced NKTCL
A Phase 3 study testing GELAD regimen, MEDA regimen and LEAP regimen in people with Extranodal NK/T-cell Lymphoma, run by Rong Tao at 1 site in China.
Trial summary
This is a randomized, open-label, prospective, multicenter phase III superiority study in patients with newly diagnosed stage IV extranodal NK/T-cell lymphoma. The study compares two frontline induction strategies followed by consolidation with autologous hematopoietic stem cell transplantation in patients who achieve… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Extranodal NK/T-cell Lymphoma
- What is being tested?
- GELAD regimen, MEDA regimen and LEAP regimen
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteChina
- Study dates
- 11 Aug 2026to 31 Dec 2031
- Phase
- Phase 3
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 to 70 years at the time of signing informed consent.
- Histologically confirmed extranodal NK/T-cell lymphoma according to the current classification criteria, with tumor tissue confirmed to be EBER positive. Central pathology review is recommended.
- Stage IV disease according to Lugano 2014 staging criteria, with baseline staging including PET/CT and bone marrow evaluation.
- Previously untreated disease, with no prior systemic anti-lymphoma therapy, radiotherapy, or other anti-tumor treatment for NKTCL.
- At least one evaluable lesion assessable by PET/CT and/or contrast-enhanced CT/MRI.
- Eastern Cooperative Oncology Group performance status score of 0 to 3.
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- Adequate hematologic function during screening, defined as absolute neutrophil count ≥1.0 × 10^9/L, hemoglobin >80 g/L, and platelet count >50 × 10^9/L.
- Adequate hepatic and renal function during screening, defined as alanine aminotransferase and aspartate aminotransferase ≤2 × upper limit of normal, total bilirubin ≤2 × upper limit of normal, and creatinine clearance ≥60 mL/min.
- No severe uncontrolled coagulation disorder, and judged by the investigator to be able to receive pegaspargase-containing therapy.
- Judged by the investigator to have no absolute contraindication to key components of the assigned treatment strategy, including irreversible contraindication to high-dose methotrexate, severe organ dysfunction precluding transplant evaluation, or other conditions clearly preventing completion of the protocol-defined strategy.
- Written informed consent provided by the participant or legally authorized representative.
Who cannot join
- Prior systemic anti-lymphoma therapy, radiotherapy, or investigational anti-tumor therapy.
- Active central nervous system lymphoma involvement, including active brain parenchymal, meningeal, cerebrospinal fluid, or intraocular involvement.
- Active infection requiring intensive care support, or infection judged by the investigator to be uncontrolled and likely to significantly interfere with protocol treatment.
- Known history of acute or chronic pancreatitis, or any condition judged by the investigator to be an absolute contraindication to pegaspargase.
- Fulminant disseminated intravascular coagulation, or severe coagulation disorder judged by the investigator to be uncorrectable in the short term and to substantially increase treatment risk.
- Severe cardiac, pulmonary, hepatic, renal, or other major organ dysfunction that, in the investigator's judgment, would significantly interfere with protocol treatment.
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- Irreversible contraindication to high-dose methotrexate, including but not limited to marked renal failure, inability to receive standardized hydration, alkalization, leucovorin rescue, or methotrexate clearance monitoring, or any condition judged by the investigator to prevent safe administration of methotrexate within the protocol-defined strategy.
- Active hepatitis C virus infection, human immunodeficiency virus infection, or active uncontrolled hepatitis B virus replication.
- Uncontrolled severe hypertension, active bleeding, recent major thromboembolic event, or vascular high-risk condition judged by the investigator to preclude safe administration of anlotinib.
- Pregnant or breastfeeding women, or participants of reproductive potential unwilling to use effective contraception during the study.
- Any other medical, psychological, social, or compliance-related condition that, in the investigator's judgment, makes the participant unsuitable for this study.
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, 1 recruiting
- Recruiting
Fudan University Shanghai Cancer Center,
Shanghai, Shanghai Municipality, 200433
Rong Tao, MD & PhD, 008621-64175590 ext. 660103, hkutao@hotmail.com
Chuanxu Liu, MD& PhD, 008621-64175590 ext. 660103, liuchaunxu@shca.or.cn
About this study
Official title: BRIDGE-NK: A Randomized, Open-Label, Prospective Phase III Study of Immunotherapy Induction Versus Chemotherapy Induction Followed by Autologous Hematopoietic Stem Cell Transplantation Consolidation in Newly Diagnosed Advanced Extranodal NK/T-Cell Lymphoma
This is a randomized, open-label, prospective, multicenter phase III superiority study in patients with newly diagnosed stage IV extranodal NK/T-cell lymphoma. The study compares two frontline induction strategies followed by consolidation with autologous hematopoietic stem cell transplantation in patients who achieve a protocol-defined strict complete remission.
Eligible participants will be randomized 1:1 to Arm A or Arm B, stratified by three-level PINK-E risk category. Arm A consists of one cycle of GELAD induction followed by three cycles of MEDA chemotherapy. Participants who achieve strict complete remission after key response assessment will proceed to autologous hematopoietic stem cell transplantation consolidation. Arm B consists of four cycles of LEAP induction with sintilimab, pegaspargase, and anlotinib. Participants who achieve strict complete remission will receive high-dose methotrexate CNS-directed consolidation followed by autologous hematopoietic stem cell transplantation consolidation if eligible.
The primary endpoint is event-free survival within 24 months after randomization. Secondary endpoints include progression-free survival, overall survival, overall response rate, complete remission rate, strict complete remission rate, autologous hematopoietic stem cell transplantation completion rate, cumulative incidence of relapse, grade 3 or higher adverse events, treatment discontinuation, treatment-related mortality, and plasma EBV-DNA clearance dynamics.
Read the detailed description
Extranodal NK/T-cell lymphoma is an aggressive Epstein-Barr virus-associated lymphoma with poor outcomes in advanced-stage disease. High-dose methotrexate-containing asparaginase-based chemotherapy can induce responses but is limited by early toxicity, organ dysfunction, infection risk, and incomplete treatment delivery in patients with high tumor burden. PD-1 antibody-based immunotherapy combinations have shown promising activity and tolerability in advanced-stage disease, but randomized evidence comparing immunotherapy induction with chemotherapy induction in a frontline curative-intent strategy remains lacking.
This study is designed to evaluate whether immunotherapy induction followed by CNS-directed high-dose methotrexate consolidation and autologous hematopoietic stem cell transplantation can improve event-free survival compared with a conventional chemotherapy induction strategy followed by autologous hematopoietic stem cell transplantation. The comparison focuses on the entire treatment strategy, including induction depth, feasibility of subsequent consolidation, and early strategy failure, rather than isolated response to a single regimen.
Strict complete remission is defined as all of the following: complete metabolic remission on PET/CT according to Lugano 2014 criteria, negative plasma EBV-DNA, and negative EBER staining on repeat bone marrow biopsy for participants with baseline bone marrow involvement.
- Conditions
- Extranodal NK/T-cell Lymphoma
- Being tested
- GELAD regimen, MEDA regimen, LEAP regimen, High-dose methotrexate, Autologous Hematopoietic Stem Cell Transplantation
- Keywords
- Extranodal NK/T-cell lymphoma, Epstein-Barr virus, Sintilimab, Pegaspargase, Anlotinib, Methotrexate, Autologous hematopoietic stem cell transplantation
- Medical subject headings
- Lymphoma, Extranodal NK-T-Cell, Epstein-Barr Virus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GELAD regimenDrug
Gemcitabine 1.0 g/m² on day 1, etoposide 60 mg/m² on days 1-3, pegaspargase 2000 IU/m² on day 4, and dexamethasone 40 mg on days 1-4, repeated every 21 days for 1 cycle.
MEDA regimenDrug
Methotrexate 3.0 g/m² on day 1 as a 3-hour intravenous infusion, etoposide 100 mg/m² on days 2-4, dexamethasone 40 mg on days 1-4, and pegaspargase 2500 IU/m² on day 4, repeated every 21 days for 3 cycles.
LEAP regimenDrug
Sintilimab 200 mg intravenously on day 1, pegaspargase 2500 IU/m² on day 1 with a maximum single dose of 3750 IU, and anlotinib 8 mg orally on days 1-14, repeated every 21 days for 4 cycles.
High-dose methotrexateDrug
Participants who achieve strict complete remission after LEAP induction will receive methotrexate 3.0 g/m² as a 3-hour intravenous infusion every 2 weeks for up to 3 doses, with hydration, urine alkalization, leucovorin rescue, and methotrexate concentration monitoring.
Autologous Hematopoietic Stem Cell TransplantationProcedure or surgery
Participants achieving strict complete remission will undergo autologous hematopoietic stem cell transplantation according to institutional transplant procedures if eligible.
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Chemotherapy Induction Followed by Autologous HSCT Consolidation | Active comparator | Participants randomized to Arm A will receive one 21-day cycle of GELAD induction followed by three 21-day cycles of MEDA chemotherapy. After completion of GELAD ×1 plus MEDA ×3, participants will undergo key response assessment with PET/CT, plasma EBV-DNA testing, and repeat bone marrow biopsy with EBER staining if bone marrow was involved at baseline. Participants who achieve strict complete remission will proceed to autologous hematopoietic stem cell transplantation consolidation if eligible. Participants who do not achieve strict complete remission and require non-protocol anti-tumor therapy will be managed according to the protocol-defined event rules. Receives: Drug: GELAD regimen; Drug: MEDA regimen; Procedure: Autologous Hematopoietic Stem Cell Transplantation |
| Arm B: Immunotherapy Induction Followed by HD-MTX and Autologous HSCT Consolidation | Experimental | Participants randomized to Arm B will receive four 21-day cycles of LEAP induction with sintilimab, pegaspargase, and anlotinib. After completion of LEAP ×4, participants will undergo key response assessment with PET/CT, plasma EBV-DNA testing, and repeat bone marrow biopsy with EBER staining if bone marrow was involved at baseline. Participants who achieve strict complete remission will receive high-dose methotrexate CNS-directed consolidation for up to 3 doses, followed by autologous hematopoietic stem cell transplantation consolidation if eligible. Receives: Drug: LEAP regimen; Drug: High-dose methotrexate; Procedure: Autologous Hematopoietic Stem Cell Transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-Free Survival Within 24 Months
Event-free survival is defined as the time from the date of randomization to the first occurrence of any of the following events: disease progression; death from any cause; inability to complete the assigned protocol-defined treatment strategy due to severe adverse events, persistent organ toxicity, treatment-related complications, or other unacceptable toxicity; or failure to achieve strict complete remission at the key response assessment followed by initiation of non-protocol anti-tumor therapy. Participants without an EFS event at 24 months after randomization will be administratively censored at 24 months.
Measured: From randomization to the first protocol-defined EFS event or administrative censoring at 24 months after randomization
Secondary outcomes (11)
Progression-Free Survival
Progression-free survival is defined as the time from randomization to documented disease progression, relapse after response, or death from any cause, whichever occurs first. Participants without an event will be censored at the date of the last valid disease assessment.
Measured: From randomization to disease progression, relapse, death, or last disease assessment, assessed up to 66 months
Overall Survival
Overall survival is defined as the time from randomization to death from any cause. Participants who are alive will be censored at the last date they are known to be alive.
Measured: From randomization to death or last confirmed survival status, assessed up to 66 months
Percentage of Participants With at Least One Serious Adverse Event
The percentage of participants who experience at least one serious adverse event, as defined in the study protocol, during the specified assessment period. Each participant will be counted once regardless of the number of serious adverse events experienced. Serious adverse events will be assessed by the investigator for relationship to protocol treatment.
Measured: From the first dose of protocol treatment through 30 days after the last protocol treatment, and through Day +90 after autologous HSCT for transplanted participants, assessed up to 12 months.
Percentage of Participants With at Least One Grade 3 or Higher Adverse Event
The percentage of participants who experience at least one grade 3 or higher adverse event, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Each participant will be counted once according to the highest adverse event grade experienced during the assessment period.
Measured: From first dose of protocol treatment through 30 days after the last protocol treatment, and through Day +90 after autologous HSCT for transplanted participants, assessed up to 12 months
Percentage of Participants Who Permanently Discontinue a Key Component of the Assigned Treatment Strategy Due to Adverse Events
The percentage of participants who permanently discontinue at least one key component of the assigned protocol-defined treatment strategy because of an adverse event, treatment-related toxicity, or treatment-related complication. Each participant will be counted once.
Measured: From first dose to permanent discontinuation of assigned protocol treatment, assessed up to 12 months
Strict Complete Remission Rate at Key Response Assessment
Strict complete remission rate is defined as the proportion of participants who meet all of the following criteria: complete metabolic remission on PET/CT, negative plasma EBV-DNA, and negative EBER staining on repeat bone marrow biopsy among participants with baseline bone marrow involvement.
Measured: At key response assessment after assigned induction treatment, approximately 12-20 weeks after randomization
Percentage of Participants With Treatment-Related Mortality
The percentage of participants who die from an adverse event or complication judged by the investigator to be related to protocol treatment, treatment-related supportive procedures, or autologous hematopoietic stem cell transplantation.
Measured: From first dose through 30 days after the last protocol treatment, and through Day +90 after autologous HSCT for transplanted participants, assessed up to 12 months
Percentage of Baseline Plasma EBV-DNA-Positive Participants With Plasma EBV-DNA Clearance at the Key Response Assessment
The percentage of participants with detectable plasma Epstein-Barr virus DNA at baseline who achieve plasma EBV-DNA clearance at the key response assessment. Plasma EBV-DNA will be measured using quantitative real-time polymerase chain reaction and reported in copies/mL. Plasma EBV-DNA clearance is defined as a decrease from a detectable baseline value to less than 500 copies/mL or below the lower limit of quantification of the assay. The denominator will include baseline plasma EBV-DNA-positive participants with an evaluable plasma EBV-DNA result at the key response assessment.
Measured: At the key response assessment after completion of assigned induction treatment, approximately 12 to 20 weeks after randomization.
Overall Response Rate at Key Response Assessment
Overall response rate is defined as the proportion of participants achieving complete remission or partial remission according to Lugano 2014 criteria at the key response assessment.
Measured: At key response assessment after assigned induction treatment, approximately 12-20 weeks after randomization
Percentage of Randomized Participants Who Complete Autologous Hematopoietic Stem Cell Transplantation
The percentage of all randomized participants who complete autologous hematopoietic stem cell transplantation after achieving protocol-defined strict complete remission and meeting transplant eligibility criteria. The denominator will include all randomized participants in each treatment arm.
Measured: From randomization to completion of autologous HSCT, assessed up to 12 months
Cumulative Incidence of Relapse Among Participants Who Achieve Strict Complete Remission
The cumulative incidence, expressed as a percentage, of first lymphoma relapse among participants who achieve protocol-defined strict complete remission at the key response assessment. Relapse will be assessed according to Lugano 2014 criteria using PET/CT and, where clinically indicated, contrast-enhanced CT or MRI, bone marrow evaluation, and plasma EBV-DNA testing. Death without documented relapse will be treated as a competing event.
Measured: From the date of first documented strict complete remission to relapse, death, or the last valid disease assessment, assessed up to 66 months after randomization.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2026
- Study start11 Aug 2026
- Primary completion31 Dec 2031 (estimated)
- Study completion31 Dec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Extranodal NK/T-cell LymphomaStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rong Tao
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Rong Tao, Fudan University
- Investigators
- Rong Tao, MD & PhD, Study chair, Shanghai Cancer CenterChuanxu Liu, MD & PhD, Principal investigator, Shanghai Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07678229
- Sponsor's protocol ID
- SHCA-NKT-Bridge26
- Acronym
- BRIDGE-NK
- Status last verified
- Aug 2026
- First submitted
- 16 Jun 2026
- Last updated
- 13 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: IPD sharing is currently undecided. The study team will determine whether de-identified participant-level data can be shared after study completion in accordance with institutional policy, participant consent, and applicable regulations.
Publications
Alaggio R, Amador C, Anagnostopoulos I, Attygalle AD, Araujo IBO, Berti E, Bhagat G, Borges AM, Boyer D, Calaminici M, Chadburn A, Chan JKC, Cheuk W, Chng WJ, Choi JK, Chuang SS, Coupland SE, Czader M, Dave SS, de Jong D, Du MQ, Elenitoba-Johnson KS, Ferry J, Geyer J, Gratzinger D, Guitart J, Gujral S, Harris M, Harrison CJ, Hartmann S, Hochhaus A, Jansen PM, Karube K, Kempf W, Khoury J, Kimura H, Klapper W, Kovach AE, Kumar S, Lazar AJ, Lazzi S, Leoncini L, Leung N, Leventaki V, Li XQ, Lim MS, Liu WP, Louissaint A Jr, Marcogliese A, Medeiros LJ, Michal M, Miranda RN, Mitteldorf C, Montes-Moreno S, Morice W, Nardi V, Naresh KN, Natkunam Y, Ng SB, Oschlies I, Ott G, Parrens M, Pulitzer M, Rajkumar SV, Rawstron AC, Rech K, Rosenwald A, Said J, Sarkozy C, Sayed S, Saygin C, Schuh A, Sewell W, Siebert R, Sohani AR, Tooze R, Traverse-Glehen A, Vega F, Vergier B, Wechalekar AD, Wood B, Xerri L, Xiao W. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms. Leukemia. 2022 Jul;36(7):1720-1748. doi: 10.1038/s41375-022-01620-2. Epub 2022 Jun 22.
PubMed 35732829Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA; Alliance, Australasian Leukaemia and Lymphoma Group; Eastern Cooperative Oncology Group; European Mantle Cell Lymphoma Consortium; Italian Lymphoma Foundation; European Organisation for Research; Treatment of Cancer/Dutch Hemato-Oncology Group; Grupo Espanol de Medula Osea; German High-Grade Lymphoma Study Group; German Hodgkin's Study Group; Japanese Lymphorra Study Group; Lymphoma Study Association; NCIC Clinical Trials Group; Nordic Lymphoma Study Group; Southwest Oncology Group; United Kingdom National Cancer Research Institute. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014 Sep 20;32(27):3059-68. doi: 10.1200/JCO.2013.54.8800.
PubMed 25113753Li D, Liu C, Wan J, Zhang W, Ma Y, Zhu Y, Ma L, Tian S, Ding H, Tao R. Sintilimab, pegaspargase, and anlotinib as induction therapy for advanced-stage NKTCL: a multicenter phase II study. Blood Adv. 2026 Mar 3:bloodadvances.2025018720. doi: 10.1182/bloodadvances.2025018720. Online ahead of print.
PubMed 41774854Zhu 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 34806163Liu C, Ding H, Zhu Q, Liu P, Zhu Y, Wang L, Ma Y, Zhang W, Tian S, Zhang X, Jin L, Liu L, Li Z, Hao S, Tao R. Induction with MEDA regimen and consolidation with Auto-HSCT for stage IV NKTCL patients: A prospective multicenter study. Int J Cancer. 2022 Sep 1;151(5):752-763. doi: 10.1002/ijc.34055. Epub 2022 Jun 9.
PubMed 35489026
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- BRIDGE-NK: A Randomized, Open-Label, Prospective Phase III Study of Immunotherapy Induction Versus Chemotherapy Induction Followed by Autologous Hematopoietic Stem Cell Transplantation Consolidation in Newly Diagnosed Advanced Extranodal NK/T-Cell Lymphoma
- ClinicalTrials.gov ID
- NCT07678229
- Acronym / sponsor ID
- BRIDGE-NK / SHCA-NKT-Bridge26
- Conditions
- Extranodal NK/T-cell Lymphoma
- Keywords
- Extranodal NK/T-cell lymphoma, Epstein-Barr virus, Sintilimab, Pegaspargase, Anlotinib, Methotrexate, Autologous hematopoietic stem cell transplantation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Rong TaoUniversity, hospital or other
- Study start
- 11 Aug 2026 (actual)
- Primary completion
- 31 Dec 2031 (estimated)
- Study completion
- 31 Dec 2031 (estimated)
- First posted
- 1 Jul 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 is a randomized, open-label, prospective, multicenter phase III superiority study in patients with newly diagnosed stage IV extranodal NK/T-cell lymphoma. The study compares two frontline induction strategies followed by consolidation with autologous hematopoietic stem cell transplantation in patients who achieve a protocol-defined strict complete remission.
Eligible participants will be randomized 1:1 to Arm A or Arm B, stratified by three-level PINK-E risk category. Arm A consists of one cycle of GELAD induction followed by three cycles of MEDA chemotherapy. Participants who achieve strict complete remission after key response assessment will proceed to autologous hematopoietic stem cell transplantation consolidation. Arm B consists of four cycles of LEAP induction with sintilimab, pegaspargase, and anlotinib. Participants who achieve strict complete remission will receive high-dose methotrexate CNS-directed consolidation followed by autologous hematopoietic stem cell transplantation consolidation if eligible.
The primary endpoint is event-free survival within 24 months after randomization. Secondary endpoints include progression-free survival, overall survival, overall response rate, complete remission rate, strict complete remission rate, autologous hematopoietic stem cell transplantation completion rate, cumulative incidence of relapse, grade 3 or higher adverse events, treatment discontinuation, treatment-related mortality, and plasma EBV-DNA clearance dynamics.
Detailed description
Extranodal NK/T-cell lymphoma is an aggressive Epstein-Barr virus-associated lymphoma with poor outcomes in advanced-stage disease. High-dose methotrexate-containing asparaginase-based chemotherapy can induce responses but is limited by early toxicity, organ dysfunction, infection risk, and incomplete treatment delivery in patients with high tumor burden. PD-1 antibody-based immunotherapy combinations have shown promising activity and tolerability in advanced-stage disease, but randomized evidence comparing immunotherapy induction with chemotherapy induction in a frontline curative-intent strategy remains lacking.
This study is designed to evaluate whether immunotherapy induction followed by CNS-directed high-dose methotrexate consolidation and autologous hematopoietic stem cell transplantation can improve event-free survival compared with a conventional chemotherapy induction strategy followed by autologous hematopoietic stem cell transplantation. The comparison focuses on the entire treatment strategy, including induction depth, feasibility of subsequent consolidation, and early strategy failure, rather than isolated response to a single regimen.
Strict complete remission is defined as all of the following: complete metabolic remission on PET/CT according to Lugano 2014 criteria, negative plasma EBV-DNA, and negative EBER staining on repeat bone marrow biopsy for participants with baseline bone marrow involvement.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: Chemotherapy Induction Followed by Autologous HSCT Consolidation | Active comparator | Drug: GELAD regimen, Drug: MEDA regimen, Procedure: Autologous Hematopoietic Stem Cell TransplantationParticipants randomized to Arm A will receive one 21-day cycle of GELAD induction followed by three 21-day cycles of MEDA chemotherapy. After completion of GELAD ×1 plus MEDA ×3, participants will undergo key response assessment with PET/CT, plasma EBV-DNA testing, and repeat bone marrow biopsy with EBER staining if bone marrow was involved at baseline. Participants who achieve strict complete remission will proceed to autologous hematopoietic stem cell transplantation consolidation if eligible. Participants who do not achieve strict complete remission and require non-protocol anti-tumor therapy will be managed according to the protocol-defined event rules. |
| Arm B: Immunotherapy Induction Followed by HD-MTX and Autologous HSCT Consolidation | Experimental | Drug: LEAP regimen, Drug: High-dose methotrexate, Procedure: Autologous Hematopoietic Stem Cell TransplantationParticipants randomized to Arm B will receive four 21-day cycles of LEAP induction with sintilimab, pegaspargase, and anlotinib. After completion of LEAP ×4, participants will undergo key response assessment with PET/CT, plasma EBV-DNA testing, and repeat bone marrow biopsy with EBER staining if bone marrow was involved at baseline. Participants who achieve strict complete remission will receive high-dose methotrexate CNS-directed consolidation for up to 3 doses, followed by autologous hematopoietic stem cell transplantation consolidation if eligible. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age 18 to 70 years at the time of signing informed consent.
- Histologically confirmed extranodal NK/T-cell lymphoma according to the current classification criteria, with tumor tissue confirmed to be EBER positive. Central pathology review is recommended.
- Stage IV disease according to Lugano 2014 staging criteria, with baseline staging including PET/CT and bone marrow evaluation.
- Previously untreated disease, with no prior systemic anti-lymphoma therapy, radiotherapy, or other anti-tumor treatment for NKTCL.
- At least one evaluable lesion assessable by PET/CT and/or contrast-enhanced CT/MRI.
Key exclusion criteria (11 listed)
- Prior systemic anti-lymphoma therapy, radiotherapy, or investigational anti-tumor therapy.
- Active central nervous system lymphoma involvement, including active brain parenchymal, meningeal, cerebrospinal fluid, or intraocular involvement.
- Active infection requiring intensive care support, or infection judged by the investigator to be uncontrolled and likely to significantly interfere with protocol treatment.
- Known history of acute or chronic pancreatitis, or any condition judged by the investigator to be an absolute contraindication to pegaspargase.
- Fulminant disseminated intravascular coagulation, or severe coagulation disorder judged by the investigator to be uncorrectable in the short term and to substantially increase treatment risk.
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 |
|---|---|---|
| GELAD regimenGemcitabine 1.0 g/m² on day 1, etoposide 60 mg/m² on days 1-3, pegaspargase 2000 IU/m² on day 4, and dexamethasone 40 mg on days 1-4, repeated every 21 days for 1 cycle. | Drug | Arm A: Chemotherapy Induction Followed by Autologous HSCT Consolidation |
| MEDA regimenMethotrexate 3.0 g/m² on day 1 as a 3-hour intravenous infusion, etoposide 100 mg/m² on days 2-4, dexamethasone 40 mg on days 1-4, and pegaspargase 2500 IU/m² on day 4, repeated every 21 days for 3 cycles. | Drug | Arm A: Chemotherapy Induction Followed by Autologous HSCT Consolidation |
| LEAP regimenSintilimab 200 mg intravenously on day 1, pegaspargase 2500 IU/m² on day 1 with a maximum single dose of 3750 IU, and anlotinib 8 mg orally on days 1-14, repeated every 21 days for 4 cycles. | Drug | Arm B: Immunotherapy Induction Followed by HD-MTX and Autologous HSCT Consolidation |
| High-dose methotrexateParticipants who achieve strict complete remission after LEAP induction will receive methotrexate 3.0 g/m² as a 3-hour intravenous infusion every 2 weeks for up to 3 doses, with hydration, urine alkalization, leucovorin rescue, and methotrexate concentration monitoring. | Drug | Arm B: Immunotherapy Induction Followed by HD-MTX and Autologous HSCT Consolidation |
| Autologous Hematopoietic Stem Cell TransplantationParticipants achieving strict complete remission will undergo autologous hematopoietic stem cell transplantation according to institutional transplant procedures if eligible. | Procedure or surgery | Arm A: Chemotherapy Induction Followed by Autologous HSCT Consolidation, Arm B: Immunotherapy Induction Followed by HD-MTX and Autologous HSCT Consolidation |
Primary outcome
Event-Free Survival Within 24 Months
Time frame: From randomization to the first protocol-defined EFS event or administrative censoring at 24 months after randomization
Event-free survival is defined as the time from the date of randomization to the first occurrence of any of the following events: disease progression; death from any cause; inability to complete the assigned protocol-defined treatment strategy due to severe adverse events, persistent organ toxicity, treatment-related complications, or other unacceptable toxicity; or failure to achieve strict complete remission at the key response assessment followed by initiation of non-protocol anti-tumor therapy. Participants without an EFS event at 24 months after randomization will be administratively censored at 24 months.
11 secondary outcomes
Progression-Free Survival
Time frame: From randomization to disease progression, relapse, death, or last disease assessment, assessed up to 66 months
Overall Survival
Time frame: From randomization to death or last confirmed survival status, assessed up to 66 months
Percentage of Participants With at Least One Serious Adverse Event
Time frame: From the first dose of protocol treatment through 30 days after the last protocol treatment, and through Day +90 after autologous HSCT for transplanted participants, assessed up to 12 months.
Percentage of Participants With at Least One Grade 3 or Higher Adverse Event
Time frame: From first dose of protocol treatment through 30 days after the last protocol treatment, and through Day +90 after autologous HSCT for transplanted participants, assessed up to 12 months
Percentage of Participants Who Permanently Discontinue a Key Component of the Assigned Treatment Strategy Due to Adverse Events
Time frame: From first dose to permanent discontinuation of assigned protocol treatment, assessed up to 12 months
Strict Complete Remission Rate at Key Response Assessment
Time frame: At key response assessment after assigned induction treatment, approximately 12-20 weeks after randomization
Percentage of Participants With Treatment-Related Mortality
Time frame: From first dose through 30 days after the last protocol treatment, and through Day +90 after autologous HSCT for transplanted participants, assessed up to 12 months
Percentage of Baseline Plasma EBV-DNA-Positive Participants With Plasma EBV-DNA Clearance at the Key Response Assessment
Time frame: At the key response assessment after completion of assigned induction treatment, approximately 12 to 20 weeks after randomization.
Overall Response Rate at Key Response Assessment
Time frame: At key response assessment after assigned induction treatment, approximately 12-20 weeks after randomization
Percentage of Randomized Participants Who Complete Autologous Hematopoietic Stem Cell Transplantation
Time frame: From randomization to completion of autologous HSCT, assessed up to 12 months
Cumulative Incidence of Relapse Among Participants Who Achieve Strict Complete Remission
Time frame: From the date of first documented strict complete remission to relapse, death, or the last valid disease assessment, assessed up to 66 months after randomization.
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 13 Aug 2026.
- Results publication: PubMed 35732829Alaggio R, Amador C, Anagnostopoulos I, Attygalle AD, Araujo IBO, Berti E, Bhagat G, Borges AM, Boyer D, Calaminici M, Chadburn A, Chan JKC, Cheuk W, Chng WJ, Choi JK, Chuang SS, Coupland SE, Czader M, Dave SS, de Jong D, Du MQ, Elenitoba-Johnson KS, Ferry J, Geyer J, Gratzinger D, Guitart J, Gujral S, Harris M, Harrison CJ, Hartmann S, Hochhaus A, Jansen PM, Karube K, Kempf W, Khoury J, Kimura H, Klapper W, Kovach AE, Kumar S, Lazar AJ, Lazzi S, Leoncini L, Leung N, Leventaki V, Li XQ, Lim MS, Liu WP, Louissaint A Jr, Marcogliese A, Medeiros LJ, Michal M, Miranda RN, Mitteldorf C, Montes-Moreno S, Morice W, Nardi V, Naresh KN, Natkunam Y, Ng SB, Oschlies I, Ott G, Parrens M, Pulitzer M, Rajkumar SV, Rawstron AC, Rech K, Rosenwald A, Said J, Sarkozy C, Sayed S, Saygin C, Schuh A, Sewell W, Siebert R, Sohani AR, Tooze R, Traverse-Glehen A, Vega F, Vergier B, Wechalekar AD, Wood B, Xerri L, Xiao W. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms. Leukemia. 2022 Jul;36(7):1720-1748. doi: 10.1038/s41375-022-01620-2. Epub 2022 Jun 22.
- Results publication: PubMed 25113753Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA; Alliance, Australasian Leukaemia and Lymphoma Group; Eastern Cooperative Oncology Group; European Mantle Cell Lymphoma Consortium; Italian Lymphoma Foundation; European Organisation for Research; Treatment of Cancer/Dutch Hemato-Oncology Group; Grupo Espanol de Medula Osea; German High-Grade Lymphoma Study Group; German Hodgkin's Study Group; Japanese Lymphorra Study Group; Lymphoma Study Association; NCIC Clinical Trials Group; Nordic Lymphoma Study Group; Southwest Oncology Group; United Kingdom National Cancer Research Institute. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014 Sep 20;32(27):3059-68. doi: 10.1200/JCO.2013.54.8800.
- Results publication: PubMed 41774854Li D, Liu C, Wan J, Zhang W, Ma Y, Zhu Y, Ma L, Tian S, Ding H, Tao R. Sintilimab, pegaspargase, and anlotinib as induction therapy for advanced-stage NKTCL: a multicenter phase II study. Blood Adv. 2026 Mar 3:bloodadvances.2025018720. doi: 10.1182/bloodadvances.2025018720. Online ahead of print.
- 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.
- Results publication: PubMed 35489026Liu C, Ding H, Zhu Q, Liu P, Zhu Y, Wang L, Ma Y, Zhang W, Tian S, Zhang X, Jin L, Liu L, Li Z, Hao S, Tao R. Induction with MEDA regimen and consolidation with Auto-HSCT for stage IV NKTCL patients: A prospective multicenter study. Int J Cancer. 2022 Sep 1;151(5):752-763. doi: 10.1002/ijc.34055. Epub 2022 Jun 9.
- Individual participant dataSharing planned: Undecided. IPD sharing is currently undecided. The study team will determine whether de-identified participant-level data can be shared after study completion in accordance with institutional policy, participant consent, and applicable regulations.
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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 & PhD study chair
Shanghai Cancer Center
Chuanxu Liu, MD & PhD principal investigator
Shanghai Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing GELAD regimen, MEDA regimen and LEAP regimen in people with Extranodal NK/T-cell Lymphoma, run by Rong Tao 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 11 inclusion and 11 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: looking for participants now, as of the sponsor's last update on 13 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 & PhD (008621-64175590 ext. 660103, hkutao@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event-Free Survival Within 24 Months (time frame: From randomization to the first protocol-defined EFS event or administrative censoring at 24 months after randomization). 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 NCT07678229, which also lists 5 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 13 Aug 2026.