MESA Versus ESA in the Treatment of Early Stage NK/T-cell Lymphoma

Study Overview
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Brief Summary
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Extranodal natural killer (NK)/T-cell lymphoma (ENKTL), nasal type, is a distinct and heterogeneous histopathologic subtype of non-Hodgkin lymphoma (NHL), accounting for 5% 10%. The frequency of ENKTL among NHL patients is significantly higher in Asia than in Western countries, with poor prognosis. Radiotherapy plus chemotherapy has improved the survival for these patients. But the optimal treatment schedule is controversial. The previous protocols usually contained high dose methotrexate, but the application of them is limited for the toxicity.

Detailed Description
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In mid-2016, we had the final evaluation of the phase 2 study of MESA with sandwiched radiotherapy in newly diagnosed early stage NKTCL (NCT02825147). We obtained the final overall response rate of MESA with sandwiched radiotherapy, while the 2-year progression free survival rate was not available at that timepoint. To make the study design of sample size more accurate, we changed the primary outcome endpoint from 2-year progression free survival rate to overall response rate. The change had been approved by the Ethics Committee in August 10, 2016. At that time, only fourteen patients were enrolled in NCT02631239.

Official Title
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The Efficacy and Safety of Etoposide, Dexamethasone, Peg-asparaginase or Plus Methotrexate With Sandwiched Radiotherapy in the Treatment of Stage I to II Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type

Conditions
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Extranodal NK/T-cell Lymphoma, Nasal Type

Intervention / Treatment
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* Drug: Methotrexate
* Drug: Etoposide
* Drug: Dexamethasone
* Drug: Pegaspargase
* Radiation: Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathological diagnosis of extranodal NK/T cell lymphoma, nasal type, previously untreated Age 14   70 years old ECOG(Eastern Cooperative Oncology Group）performance status 0 2 Stage I to II Life expectancy>6 months Informed consented Exclusion Criteria: Chemotherapy before Bone marrow transplantation before History of malignancy Uncontrollable cardio-cerebral vascular, coagulative, autoimmune, serious infectious disease LVEF≤50% Other uncontrollable medical condition that may that may interfere the participation of the study Lab at enrollment ALT or AST >3*ULN, AKP or bilirubin >2.5*ULN Creatinine>1.5*ULN Not able to comply to the protocol for mental or other unknown reasons Pregnant or lactation HIV infection

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 70 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: MESA<br>Methotrexate, etoposide, dexamethasone, Peg-asparaginase and sandwiched radiotherapy | Drug: Methotrexate<br>* 1g/m2/d IV *1d<br>Drug: Etoposide<br>* 200mg/d PO *3d<br>Drug: Dexamethasone<br>* 40mg/d PO *3d<br>Drug: Pegaspargase<br>* 2500IU/m2/d IM *1d<br>Radiation: Radiotherapy<br>* 50-56Gy<br>|
| Experimental: ESA<br>Etoposide, dexamethasone, Peg-asparaginase and sandwiched radiotherapy | Drug: Etoposide<br>* 200mg/d PO *3d<br>Drug: Dexamethasone<br>* 40mg/d PO *3d<br>Drug: Pegaspargase<br>* 2500IU/m2/d IM *1d<br>Radiation: Radiotherapy<br>* 50-56Gy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate |  | 21 days after 4 cycles of chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 2-year | 
| Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0 |  | Day 1 of each course and then every 3 months for 2 years | 
| Progression free survival |  | 2-year |