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BRIDGE-NK: Immunotherapy Versus Chemotherapy Induction Followed by Autologous HSCT in Advanced NKTCL

ConditionExtranodal NK/T-cell Lymphoma
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18-70
SponsorRong Tao

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • GELAD regimen

    Drug

    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 regimen

    Drug

    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 regimen

    Drug

    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 methotrexate

    Drug

    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 Transplantation

    Procedure/Surgery

    Participants achieving strict complete remission will undergo autologous hematopoietic stem cell transplantation according to institutional transplant procedures if eligible.

Treatment groups

150 Participants
are divided into 2 treatment groups
Group A: Arm A: Chemotherapy Induction Followed by Autologous HSCT ConsolidationActive comparator 3 interventions
Group B: Arm B: Immunotherapy Induction Followed by HD-MTX and Autologous HSCT ConsolidationExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

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.

Time frame
From randomization to the first protocol-defined EFS event or administrative censoring at 24 months after randomization

Secondary outcomes

1

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.

Time frame
From randomization to disease progression, relapse, death, or last disease assessment, assessed up to 66 months
2

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.

Time frame
From randomization to death or last confirmed survival status, assessed up to 66 months
3

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.

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.
4

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.

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

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Rong Tao

Lead sponsor

Fudan University

Sponsor institution

Source ClinicalTrials.gov
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