Combine GELOX With Concurrent Radiation Therapy for Patients With Stage IE/IIE ENKTL

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of first-line gemcitabine, oxaliplatin, and asparaginase (GELOX) with concurrent involved-field radiation therapy for patients in newly diagnosed stage IE/IIE ENKTL.

Detailed Description
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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 (E B V) DNA blood levels, titer of EBV antibody (EA-IgA, VCA-IgA), β2-micro globulin (β2-MG) and soluble CD 25 (sCD 25) in the serum. Recheck before and after every course: Epstein-Barr virus (EBV) DNA blood levels, titer of EBV antibody (EA-IgA, VCA-IgA), β2-micro globulin (β2-MG) and soluble CD 25 (sCD25) in the serum. Recheck every two course: 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) Treatment Protocol - The GELOX regimen consist of the following drugs: gemcitabine ：1250 mg/ m2 on days 1,ivdrip oxaliplatin ：85 mg/m2 on day 1, ivdrip pegaspargase : 2500 IU/m 2 daily on day 1,intramuscular The treatment cycle was repeated every 14 days. IFRT was delivered using 6-MeV linear accelerator using 3-dimensional conformable treatment planning. The IFRT dose was 56 grays (Gy) in 28 fractions, we define the clinical target volume of limited stage IE disease as the bilateral nasal cavity, bilateral ethmoid sinuses, and ipsilateral maxillary sinus; and the clinical target volume would extend to involved tissues for patients who had extensive stage IE disease. For patients who had stage IIE disease, the clinical target volume also, included the bilateral cervical lymph node area. Disease Progression during the treatment should be treated with second-line therapy.

Official Title
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Combination of Gemcitabine, Oxaliplatin, and Asparaginase (GELOX) With Concurrent Involved-Field Radiation Therapy for Patients With Stage IE/IIE Extranodal Natural Killer/T-Cell Lymphoma:a Phase II Study

Conditions
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Lymphoma, Extranodal NK-T-Cell

Intervention / Treatment
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* Drug: GELOX
* Radiation: IFRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: newly diagnosed ENKTL age:18-69years Ann Arbor stage IE,or stage IIE with cervical lymph node involvement at lease one measurable lesion receive no chemotherapy or radiotherapy before 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 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 respiratory

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 69 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: concurrent chemoradiotherapy with GELOX<br>GELOX: gemcitabine ：1250mg/m2 (ivdrip) on days 1, oxaliplatin :85 mg/m2 (ivdrip) on day 1, and pegaspargase : 2500 IU/m2 (intramuscular injection) on day 1.Cycle is repeated every 14 days IFRT IFRT is delivered using 6-MeV linear accelerator using 3-dimensional conformable treatment planning. The IFRT dose was 56 grays (Gy) in 28 fractions. the first cycle of chemotherapy was initiated on the same day of radiotherapy. | Drug: GELOX<br>* gemcitabine ：1250mg/m2 (ivdrip) on days 1, oxaliplatin :85 mg/m2 (ivdrip) on day 1, and pegaspargase : 2500 IU/m2 (intramuscular injection) on day 1.Cycle is repeated every 14 days<br>* Other names: pegaspargase;Radiation: IFRT<br>* IFRT is delivered using 6-MeV linear accelerator using 3-dimensional conformable treatment planning. The IFRT dose was 56 grays (Gy) in 28 fractions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| complete remission rate | 1.The criteria for the efficacy evaluation (overall response rate and complete remission) of the regimen is according to the following article. Cheson BD, Horning SJ, Coiffier B, et al. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999;17:1244. | every 4 weeks,up to completion of treatment(approximately 6 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression free survival | 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 | up to end of follow-up-phase (approximately 3 years) | 
| overall survival | 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. | up to end of follow-up-phase (approximately 3 years) | 
| safety | including hematological safety and non-hematological safety.All the adverse events will be classified according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE) | up to end of follow-up-phase (approximately 3 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GELOX, Lymphoma, Extranodal NK-T-Cell, asparaginase, concurrent chemoradiotherapy, sIL-2R