Sandwich Chemotherapy With Radiotherapy in Newly Diagnosed, Stage IE to IIE, ENKTL

Study Overview
=================
Brief Summary
-----------------
A phase 2 study was conducted of sandwich protocols, with earlier RT after an initial 2 of P-CHOP (Pegaspargase, cyclophosphamide,vincristine, doxorubicin and dexamethasone ), followed by further two consolidation cycles,to explore the appropriate mode of combined modality therapy (CMT) in early stage ENKTL.

Detailed Description
-----------------
The extranodal natural killer/T-cell lymphoma (ENKTL) shows high local or systemic failure rates when radiotherapy (RT) is taken as the primary treatment, suggesting a role for chemotherapy (CT) added to RT for this disease. However, the appropriate mode of combined modality therapy (CMT) has not been fully defined.We conducted a prospective phase II study of Sandwich Pegaspargase, cyclophosphamide,vincristine, doxorubicin and dexamethasone (P-CHOP) regimen in combination with radiotherapy.The sandwich protocols, refer to earlier RT after an initial 2 cycles of P-CHOP followed by further two consolidation cycles.

Official Title
-----------------
Phase 2 Trial of Sandwich Pegaspargase-CHOP Chemotherapy With Radiotherapy in Newly Diagnosed, Stage IE to IIE, Nasal Type, Extranodal Natural Killer/T-cell Lymphoma

Conditions
-----------------
Treatment Refusal

Intervention / Treatment
-----------------
* Drug: P-CHOP
* Radiation: Radiotherapy
* Drug: P-CHOP


Participation Criteria
=================
Eligibility Criteria
-----------------
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
-----------------
Minimum Age: 18 Years
Maximum Age: 69 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: sandwich protocols<br>sandwich protocols: Patients with newly diagnosed ENKTL is given 2 cycles of P-CHOP[cyclophosphamide(CTX), 750 mg/m2 day 1; vincristine(VCR), 1.4 mg/m2 day 1 (maximal dose 2 mg),adriamycin(ADM) 50 mg/m2 day 1; dexamethasone(DXM) 10 mg days 1-8; Pegaspargase 2500 international unit day 1] before radiotherapy(RT) and then two consolidation cycles after RT. | Drug: P-CHOP<br>* Two cycles of P-CHOP:cyclophosphamide, 750 mg/m2 day 1; vincristine,(maximal dose 2 mg),adriamycin , 50 mg/m2 day 1; dexamethasone,10mg days 1-8; Pegaspargase, 2500IU/m2 day 1 are given before radiotherapy<br>* Other names: CTX, VCR, ADM , DXM, Pegaspargase;Radiation: Radiotherapy<br>* Radiotherapy was scheduled after 2 cycles of P-CHOPregimen. Involved field radiotherapy(IFRT) is delivered using 6-Million electron Volts linear accelerator using 3-dimensional conformable treatment planning. The IFRT dose was 56 grays (Gy) in 28 fractions.<br>* Other names: radiotherapy after induction chemotherapy;Drug: P-CHOP<br>* Two consolidation cycles of P-CHOP are given after radiotherapy<br>* Other names: CTX, VCR, ADM , DXM, Pegaspargase;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| complete remission rate | The criteria for the efficacy evaluation (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 | 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 | 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) | 
| Hematological and non-hematological safety as a measure of adverse events according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE) | 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
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
extranodal natural killer/T-cell lymphoma, nasal type, radiotherapy, chemotherapy