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

Extranodal NK/T-cell Lymphoma,Nasal-type, Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02229682
• Other study ID #: SYSUCC-NKTRT-01
• Status: Not yet recruiting
• Phase: Phase 2
• First received: August 27, 2014
• Last updated: September 28, 2014
• Start date: October 2014
• Est. completion date: October 2019

Study information

• Verified date: September 2014
• Source: Sun Yat-sen University
• Contact: Yujing ZHANG, MD/PHD
• Phone: 86-20-87343702
• Email: zhangyj[@]sysucc.org.cn
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

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 (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).

2. Treatment Protocol:

1. 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.

2. 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: October 2019
• Est. primary completion date: October 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Radiation:
• Mild-dose 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.

Locations

Country	Name	City	State
China	Dept. Radiation Oncology, Sun Yat-sen University Cancer Center	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (2)

Grégoire V, Ang K, Budach W, Grau C, Hamoir M, Langendijk JA, Lee A, Le QT, Maingon P, Nutting C, O'Sullivan B, Porceddu SV, Lengele B. Delineation of the neck node levels for head and neck tumors: a 2013 update. DAHANCA, EORTC, HKNPCSG, NCIC CTG, NCRI, RTOG, TROG consensus guidelines. Radiother Oncol. 2014 Jan;110(1):172-81. doi: 10.1016/j.radonc.2013.10.010. Epub 2013 Oct 31. — View Citation

Wang L, Wang ZH, Chen XQ, Li YJ, Wang KF, Xia YF, Xia ZJ. First-line combination of gemcitabine, oxaliplatin, and L-asparaginase (GELOX) followed by involved-field radiation therapy for patients with stage IE/IIE extranodal natural killer/T-cell lymphoma. Cancer. 2013 Jan 15;119(2):348-55. doi: 10.1002/cncr.27752. Epub 2012 Jul 18. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	No
Secondary	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	No
Secondary	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	No