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

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

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.

Study Overview

• Status: Unknown
• Conditions: Lymphoma, Extranodal NK-T-Cell
• Intervention / Treatment: Drug: GELOX; Radiation: IFRT

Detailed Description

1. 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)

2. 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.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China,
      • Principal Investigator: Jun Zh Xia, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 69 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: concurrent chemoradiotherapy with GELOX; 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; 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; Other Names: oxaliplatin; gemcitabine; asparaginase; pegaspargase; Radiation: 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

What is the study measuring?

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)

Other Outcome Measures

Outcome Measure	Time Frame
Epstein-Barr virus(EBV) DNA copies	Time Frame: every 3 weeks,up to completion of treatment(approximately 6 months)
Plasma β2-microglobulin	every 3 weeks,up to completion of treatment(approximately 6 months)
serum sIL-2R level	every 3 weeks,up to completion of treatment(approximately 6 months)

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: ZhongJun Xia, MD/PHD, Department of Hematological Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China,

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (ANTICIPATED): December 1, 2016
• Study Completion (ANTICIPATED): March 1, 2017

Study Registration Dates

• First Submitted: March 2, 2014
• First Submitted That Met QC Criteria: March 4, 2014
• First Posted (ESTIMATE): March 6, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): April 20, 2016
• Last Update Submitted That Met QC Criteria: April 18, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: asparaginase; concurrent chemoradiotherapy; sIL-2R; Lymphoma, Extranodal NK-T-Cell; GELOX
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Lymphoma; Lymphoma, Extranodal NK-T-Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine; Oxaliplatin; Asparaginase; Pegaspargase
• Other Study ID Numbers: GELOX1