Trial Title:
Screening Study of Combined Sequential Chemotherapy and Radiation Therapy for Early-stage NK/T-cell Lymphoma
NCT ID:
NCT06314334
Condition:
Natural Killer/T-Cell Lymphoma, Nasal and Nasal-Type
Conditions: Official terms:
Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Pegaspargase
Conditions: Keywords:
Chemotherapy
Radiation therapy
Immune checkpoint inhibitor
Pegaspargase
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Participants were stratified according to the NRI prognostic index obtained from the
baseline assessment (NRI <2, NRI ≥2) and randomly assigned to three groups receiving
different experimental treatments.
Group A (synchronous treatment group) received 4 cycles of Sintilimab combined with
pegaspargase therapy. Concurrently, they received radiotherapy treatment. Group B
(sequential treatment group) received 4 cycles of the PGEMOX regimen chemotherapy with
sequential radiotherapy.
Group C (sandwiched radiotherapy group) received 2 cycles of the GELAD regimen
chemotherapy initially, followed by radiotherapy and another two cycles GELAD
chemotherapy.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Sintilimab+Pegaspargase
Description:
1. Sintilimab, 200mg intravenous drip, on day 1;
2. pegaspargase, 2000U/m^2, capped at 3750U, intramuscular, day 1;
Arm group label:
Group A (synchronous treatment group)
Intervention type:
Drug
Intervention name:
P-GemOx
Description:
1. pegaspargase 2000U/m^2, capped at 3750U on day 1, intramuscular;
2. gemcitabine 1.0g/m^2 on day 1 and day 8, intravenous drip;
3. oxaliplatin 130mg/m^2 on day 1, intravenous drip
Arm group label:
Group B (sequential treatment group)
Intervention type:
Drug
Intervention name:
GELAD
Description:
1. gemcitabine 1.0g/m^2 on day 1, intravenous drip;
2. etoposide 60mg/m^2 on day 1-3, intravenous drip;
3. pegaspargase 2000U/m^2, capped at 3750U on day 1,intramuscular;
4. dexamethasone 20mg on day 1-4, intravenous drip.
Arm group label:
Group C (sandwiched radiotherapy group)
Intervention type:
Radiation
Intervention name:
IMRT
Description:
Intensity modulated radiotherapy (50-56Gy)
Arm group label:
Group A (synchronous treatment group)
Arm group label:
Group B (sequential treatment group)
Arm group label:
Group C (sandwiched radiotherapy group)
Summary:
Extranodal NK/T-cell lymphoma, nasal type (NKTCL) is a common malignant tumor in East
Asian populations, often starting in the nasal cavity and spreading to other organs.
Associated with EBV infection, NKTCL is aggressive. Early-stage patients typically
receive chemo and radiotherapy, with promising outcomes. Recent studies show the
potential of immune checkpoint inhibitors in NKTCL treatment. However, optimal treatment
sequencing and efficacy remain unclear. This study aims to compare three strategies: (A)
Pegaspargase with Sintilimab and radiotherapy; (B) chemo then radiotherapy (PGemOx); (C)
sandwich chemoradiotherapy (GELAD). The goal is to identify the best treatment based on
24-month progression-free survival.
Detailed description:
Extranodal NK/T-cell lymphoma, nasal type (NKTCL) is a malignant hematological tumor that
is common in East Asian populations. The disease typically manifests in the nasal cavity
in its early stages and can later involve multiple organs throughout the body. Highly
associated with EBV infection, NKTCL is known for its aggressive nature. Currently,
early-stage patients usually undergo combined treatment with chemotherapy and
radiotherapy. Recent studies have shown that combining chemotherapy and radiotherapy
containing asparaginase can achieve a complete remission rate (CR) of over 80%, with
long-term survival rates exceeding 70% for patients. In recent years, researchers have
found that immune checkpoint inhibitors demonstrate high activity in NKTCL, becoming an
important therapeutic option. However, it is worth noting that the optimal sequence of
chemotherapy and radiotherapy, as well as the effectiveness of combining radiotherapy
with immunotherapy, have not been defined. Studies on different treatment strategies have
shown variations in treatment-related adverse reactions and compliance with regimens
among patients. However, there is currently no prospective randomized controlled study
comparing the efficacy and safety of different strategies. Therefore, it is necessary to
identify a treatment strategy with good efficacy and tolerability for patients. This
study will stratify early-stage NKTCL patients using the NRI scoring system and randomly
assign them to three different treatment strategies: (A) asparaginase combined with
Sintilimab and synchronous radiotherapy; (B) sequential chemotherapy (PGemOx) followed by
radiotherapy ; (C) chemotherapy (GELAD) with sandwiched chemoradiotherapy, to identify
the best or worst treatment strategy based on the 24-month progression-free survival
rate.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients who meet the diagnostic criteria for NKTCL (WHO-2016) based on pathological
examination.
- Primary lesions located in the upper respiratory and digestive tract such as the
nasal cavity, sinuses, nasopharynx, oropharynx, or oral cavity, with clinical
staging of IE/IIE based on PET/CT and bone marrow examination according to the
Lugano 2014 criteria.
- Evaluated for lymphoma response according to the Lugano 2014 criteria, with at least
one measurable lesion or lesion assessable by PET/CT.
- No prior treatment with chemotherapy, radiotherapy, immunotherapy, or biological
therapy for lymphoma.
- Age between 18 and 75 years, both genders.
- Eastern Cooperative Oncology Group performance status (ECOG) score of 0-2.
- Must have adequate organ and bone marrow function, defined as follows:
Hematology: Absolute neutrophil count (ANC) ≥1.0×10^9/L, platelet count (PLT) ≥75×10^9/L,
hemoglobin (Hb) ≥90g/L; no administration of granulocyte colony-stimulating factor,
platelet transfusion, or red blood cell transfusion in the previous 14 days.
Liver function: Total bilirubin (TBIL) ≤1.5 times the upper limit of normal (ULN);
alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2×ULN.
Renal function: Serum creatinine (Cr) ≤1.5×ULN. Coagulation function: Plasma fibrinogen
≥1.5g/L. Cardiac function: Left ventricular ejection fraction (LVEF) ≥50%, no acute
myocardial infarction, arrhythmia, or atrioventricular conduction block of grade I or
above on electrocardiogram.
- Willing to comply with the study protocol, follow-up plan, and laboratory and
ancillary investigations.
Exclusion Criteria:
- Patients co-infected with HCV, HIV, or HBV with plasma HBV-DNA >10^3/ml.
- Patients with a history of pancreatitis.
- Patients with acute or systemic infections requiring intravenous antibiotic therapy.
- Patients with severe complications such as hemophagocytic syndrome, DIC, etc.
- Significant organ dysfunction: such as respiratory failure, chronic congestive heart
failure with NYHA class ≥2, decompensated liver or renal dysfunction, uncontrolled
hypertension and diabetes despite aggressive treatment, and cardiovascular
thrombotic or hemorrhagic events in the past 6 months.
- Patients with a history of autoimmune diseases who are not suitable for treatment
with immune checkpoint inhibitors.
- Pregnant and lactating women.
- Patients with psychiatric disorders.
- Known allergies to drugs in the chemotherapy regimen.
- Patients with concomitant other tumors requiring surgery or chemotherapy within the
past 6 months.
- Currently using other experimental drugs.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Fudan University Shanghai Cancer Center
Address:
City:
Shanghai
Zip:
200032
Country:
China
Status:
Recruiting
Contact:
Last name:
Rong Tao, MD
Phone:
8621-64175590
Email:
rtao@shca.org.cn
Contact backup:
Last name:
Chuanxu Liu, MD
Phone:
8621-64175590
Email:
liuchuanxu@shca.org.cn
Investigator:
Last name:
Rong Tao, MD
Email:
Principal Investigator
Start date:
March 4, 2023
Completion date:
December 30, 2028
Lead sponsor:
Agency:
Fudan University
Agency class:
Other
Source:
Fudan University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06314334
