Mild-dose IMRT for Early-staged Extranodal Nasal-type NK/T-cell Lymphoma With CR Tumor After GELOX Chemotherapy

Study Overview
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Brief Summary
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This study is to make sure whether reduced-dose radiation treatment is sufficient to control the disease in patients with early-staged extranodal nasal-type NK/T-cell lymphoma, who have got complete remission tumor after chemotherapy in a new and more effective asparaginase-based GELOX regimen

Detailed Description
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Definitive radiotherapy(RT) is mainstay in combined-modality treatment for patients with early-staged extranodal nasal-type NK/T-cell lymphoma(ENKTL),it can be used upfront or after short courses of chemotherapy. The typical dose of RT is recommended as 50-56Gy in conventional fractionations with 3 dimensional conformal RT or intensity-modulated radiation treatment(IMRT). Asparaginase-based chemotherapy regimens are being investigated, and primary results showed superior to previous anthracycline-based (eg. CHOP) chemotherapy. GELOX is a new asparaginase-based chemotherapy regimen designed and published in our institute, and the rate of complete remission(CR) is well improved. We hypothesis the reduced-dose radiation treatment(IMRT in 46Gy) is sufficient to control the disease in patients with early-staged ENKTL, who have got CR after GELOX chemotherapy, and to validate in this phase II study. Patients: All patients should sign a written informed consent form before enrollment, and the study should be approved by the Sun Yat-sen University Cancer Center Ethics Board. Baseline of patients: Computed tomography (CT) scans of the chest, abdomen, and pelvis, magnetic resonance imaging studies of the head and neck, and bilateral bone marrow aspiration or biopsy. Positron emission tomography-CT scans (optional). Epstein-Barr virus (EBV) DNA blood levels, titer of EBV antibody (EA-IgA, VCA-IgA). Recheck before and after GELOX chemotherapy and IMRT: Epstein-Barr virus (EBV) DNA blood levels, titer of EBV antibody (EA-IgA, VCA-IgA), computed tomography (CT) scans of the chest, abdomen, and pelvis, magnetic resonance imaging studies of the head and neck, positron emission tomography-CT scans (optional). Treatment Protocol: The GELOX regimen consist of the following drugs: gemcitabine：1250 mg/ m2 on days 1,iv drip; oxaliplatin：85 mg/m2 on day 1, iv drip; pegaspargase: 2500 IU/m 2 daily on day 1,intramuscular. The treatment cycle is repeated every 14 days. IMRT is delivered using 6-8MeV linear accelerator using extended involved-field intensity-modulated radiation treatment planning. The RT dose is 46.2 grays (Gy) in 22 fractions, and a simultaneous-boost method is used. We assign gross tumor volume (GTV) to 46.2Gy/22F, which is delineated according to the initial gross tumor volume identified with imaging and physical examination, including the primary tumor and involved regional lymph nodes. The high-risk clinical target volume (CTV1) is assigned to 41.8Gy/22F, which is delineated including the first batch of adjacent structures around GTV, and lymph node group apt for involvement according to clinical feature of individual tumors. The low-risk clinical target volume (CTV2) is assigned to 36.3Gy/22F, which is delineated including the extrapolated structures outside of CTV1 sites, and LN groups adjacent to CTV1 LN groups.

Official Title
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Mild-dose Intensity-modulated Radiation Treatment for Stage IE/IIE Extranodal Nasal-type NK/T-cell Lymphoma With Complete Remission Tumor After Combination of Gemcitabine, Oxaliplatin, and Asparaginase (GELOX) Chemotherapy:a Phase II Study

Conditions
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Lymphoma,, Non-Hodgkin Lymphoma,, Extranodal NK/T-cell Lymphoma,Nasal-type,

Intervention / Treatment
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* Radiation: Mild-dose IMRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: newly diagnosed ENKTL age:18-75years Ann Arbor stage IE,or stage IIE with cervical lymph node involvement at lease one measurable lesion received GELOX chemotherapy and got CR before radiotherapy Eastern CooperativeOncology Group performance status of 0 to 2 Adequate hematologic function (eg, white blood cell ≥ 3×10e9/l,neutrophils count ≥1.5×10e9/L, and platelet count≥ 100×10e9/L),renal function (eg, serum creatinine≤1.5 mg/dL and creatinine clearance ≥50 mL minute), and hepatic function (e.g, total bilirubin≤ 2 times the upper limit of normal and aspartate and alanine transaminase levels ≤ 3 times the upper limit of normal) Exclusion Criteria: mismatch the inclusion criteria, got non-CR after GELOX chemotherapy before IMRT, systematic central nervous system involvement, previous or concomitant malignancies and any coexisting medical problems that could cause poor compliance with the study protocol, primary lesion not from the upper aerodigestive tract

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mild-dose IMRT<br>Experimental: Mild-dose of 46Gy with IMRT Drug: gemcitabine：1250mg/m2 (iv drip) on days 1, oxaliplatin: 85 mg/m2 (iv drip) on day 1, and pegaspargase: 2500 IU/m2 (intramuscular injection) on day 1. Cycle is repeated every 14 days IMRT： IMRT is delivered using 6-8 MeV linear accelerator using intensity-modulated radiation treatment planning. The radiation dose is 46.2 grays (Gy) in 22 fractions. | Radiation: Mild-dose IMRT<br>* IMRT is delivered using 6-8 MeV linear accelerator using intensity-modulated radiation treatment planning. The radiation dose is 46.2 grays (Gy) in 22 fractions.<br>* Other names: Mild-dose intensity-modulated radiation treatment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| loco-regional tumor control | loco-regional tumor control was examined with physical examination and image methods. | every 3 months after IMRT for 2 years, and then every 6 months for the next 3 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival(PFS) | progression-free survival(PFS): time from the date of enrollment to date of disease progression, or death of any cause, or date of lost follow-up, whichever comes first | every 3 months after IMRT for 2 years, and then every 6 months for the next 3 years | 
| overall survival(OS) | overall survival (OS): time from the date of enrollment to date of death from any cause, or date of lost follow-up, whichever comes first. | every 3 months after IMRT for 2 years, and then every 6 months for the next 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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extranodal NK/T-cell lymphoma,nasal-type,, radiotherapy,, intensity-modulated radiation treatment,, asparaginase-based chemotherapy,, loco-regional control,, survival