Screening Study of Combined Sequential Chemotherapy and Radiation Therapy for Early-stage NK/T-cell Lymphoma

NCT06314334 | Recruiting Phase 2 DMC

• 1 other identifier: SHCA-NKT-202301
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 7

Brief 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.

Conditions

Natural Killer/T-Cell Lymphoma, Nasal and Nasal-Type

Keywords

Chemotherapy; Radiation therapy; Immune checkpoint inhibitor; Pegaspargase

Outcome Measures

Primary Outcomes (1)

• PFS24

  Rate of patients with 24-month progression-free survival

  From date of randomization until the date of first documented progression, assessed up to 24 months by the Lugano 2014 response criteria.

Secondary Outcomes (4)

• ORR

  response rate at 24th week

• OS

  From the time of patient randomization to the end of study, assessed up to 60 months

• EFS

  From the time of patient randomization to the end of study, assessed up to 60 months

• TRAE

  From the time of patient randomization to the end of study, assessed up to 60 months

Study Arms (3)

Group A (synchronous treatment group)

EXPERIMENTAL

Patients received 4 cycles of Sintilimab combined with pegaspargase therapy, with each cycle lasting 3 weeks, for a total of 4 cycles. Concurrently, they received radiotherapy treatment (IMRT, 50-56Gy, starting within 21 days after the first Sintilimab treatment).

Drug: Sintilimab+Pegaspargase; Radiation: IMRT

Group B (sequential treatment group)

EXPERIMENTAL

Patients received 4 cycles of the PGEMOX regimen chemotherapy. Each cycle lasted 3 weeks, with sequential radiotherapy (IMRT, 50-56Gy) administered within 4 weeks after the last chemotherapy cycle.

Drug: P-GemOx; Radiation: IMRT

Group C (sandwiched radiotherapy group)

EXPERIMENTAL

Patients received 2 cycles of the GELAD regimen chemotherapy initially, with each cycle lasting 3 weeks. After the second cycle of chemotherapy, radiotherapy (IMRT, 50-56Gy) was administered within 4 weeks. Following the completion of radiotherapy, they received an additional 2 cycles of the GELAD regimen chemotherapy.

Drug: GELAD; Radiation: IMRT

Interventions

GELAD DRUG

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.

Group C (sandwiched radiotherapy group)

IMRT RADIATION

Intensity modulated radiotherapy (50-56Gy)

Group A (synchronous treatment group); Group B (sequential treatment group); Group C (sandwiched radiotherapy group)

P-GemOx DRUG

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

Group B (sequential treatment group)

Sintilimab+Pegaspargase DRUG

1. Sintilimab, 200mg intravenous drip, on day 1; 2. pegaspargase, 2000U/m\^2, capped at 3750U, intramuscular, day 1;

Group A (synchronous treatment group)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (7)

Cancer Hospital of Fujian Province

Fuzhou, Fujian, 350003, China

RECRUITING

Nantong Cancer Hospital

Nantong, Jiangsu, 226006, China

RECRUITING

Shanghai Eye Ear Nose and Throat Hospital，Fudan University

Shanghai, Shanghai Municipality, 200000, China

RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200092, China

RECRUITING

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

RECRUITING

People's Hospital of Ningbo University

Ningbo, Zhejiang, China

RECRUITING

Related Publications (3)

• Zhu 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.

  PMID: 34806163 BACKGROUND

• Zhang Y, Ma S, Cai J, Yang Y, Jing H, Shuang Y, Peng Z, Li B, Liu P, Xia Z, Xia Y, Gao Y, Chen D, Lin J, Li Q, Xu S, Xu Q, Zhang H, Huang H, Cai Q. Sequential P-GEMOX and radiotherapy for early-stage extranodal natural killer/T-cell lymphoma: A multicenter study. Am J Hematol. 2021 Nov 1;96(11):1481-1490. doi: 10.1002/ajh.26335. Epub 2021 Sep 13.

  PMID: 34449095 BACKGROUND

• Wang H, Wang L, Li C, Wuxiao Z, Chen G, Luo W, Lu Y. Pegaspargase Combined with Concurrent Radiotherapy for Early-Stage Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type: A Two-Center Phase II Study. Oncologist. 2020 Nov;25(11):e1725-e1731. doi: 10.1634/theoncologist.2020-0144. Epub 2020 Jul 29.

  PMID: 32627928 BACKGROUND

Study Officials

• Rong Tao, MD

  Fudan Cancer Hospital

  STUDY CHAIR

Central Study Contacts

Rong Tao, MD

CONTACT

8621-64175590; rtao@shca.org.cn

Chuanxu Liu, MD

CONTACT

021-64175590; liuchuanxu@shca.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Model Details: 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.

Study Record Dates

• First Submitted: March 8, 2024
• First Posted: March 18, 2024
• Study Start: March 4, 2024
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2028
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (7)