GELAD Chemotherapy and Sandwiched Radiotherapy in the Treatment of Stage IE/IIE Natural Killer/T-cell Lymphoma

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of gemcitabine, etoposide, pegaspargase and dexamethasone (GELAD) chemotherapy and sandwiched radiotherapy as first-line treatment in patients with de novo stage IE/IIE extranodal natural killer/T-cell lymphoma, nasal type.

Detailed Description
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Extranodal natural killer/T-cell lymphoma (ENKTCL), nasal type, is a rare subtype of non-Hodgkin lymphoma (NHL) with relatively high incidence in China. Radiotherapy alone for stage IE/IIE diseases has good response rate but with high relapse rates, ranging from 20-50%. The combination of chemotherapy and radiotherapy improved the long-term survival for patients with stage IE/IIE diseases. But the optimal treatment schedule has not been established. This study is designed with two cycles GELAD chemotherapy, followed by 50-56Gy radiotherapy, and completed with additional two cycles GELAD chemotherapy. The efficacy and safety of this sandwiched chemoradiotherapy in the treatment of stage IE/IIE ENKTCL will be measured.

Official Title
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The Efficacy and Safety of Gemcitabine, Etoposide, Dexamethasone and Pegaspargase Chemotherapy (GELAD) With Sandwiched Radiotherapy in the Treatment of Stage IE/II Natural Killer/T-Cell Lymphoma: A Multicenter, Prospective Study

Conditions
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Extranodal NK-T-Cell Lymphoma, Nasal Type

Intervention / Treatment
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* Drug: GELAD
* Radiation: Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathological diagnosis of extranodal natural killer/T-cell lymphoma, nasal type, previously untreated Eastern Cooperative Oncology Group (ECOG ) performance status 0 3 Stage IE to IIE disease with at least one measurable lesion in the nasal cavity, paranasal sinuses, orbit, pharynx, Waldeyer's ring, or oral cavity. Preserved organ functions for: absolute neutrophil counter (ANC)>1.0×109/L, Platelet>50×109/L, hemoglobin>80g/L, total bilirubin (TBIL)<2×ULN, alanine transaminase (ALT)<2×ULN, serum creatinine<1.5×ULN，fibrinogen≥1.0g/L, LVEF≥50% No history of chemotherapy or radiotherapy. Signed Informed consented Exclusion Criteria: Concurrent cancers need surgery or chemotherapy within 6 months. Significant complications: LVEF≤50%, coagulopathy, autoimmune disease, severe infection, or liver cirrhosis, hemophagocytic lymphohistiocytosis. Mental disorders. Pregnant or lactation HIV, hepatitis virus C (HCV), or active hepatitis virus B (HBV) infection with HBV DNA≥105 copies/ml. History of pancreatitis Known history for grade 3/4 allergy to the drugs in chemotherapy regimen. Enrolled in other trial treatment

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 75 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: GELAD/Radiation<br>Patients will be initially treated with two cycles GELAD chemotherapy, followed by 50-56Gy radiotherapy, and completed with another two cycles GELAD chemotherapy. GELAD chemotherapy will be repeated every 21 days. Radiotherapy will be delivered in 25-32 fractions. | Drug: GELAD<br>* Gemcitabine, 1.0g/m2/d IV, day 1 Etoposide, 60mg/m2 IV, day 1 to day 3 Dexamethasone, 40mg/d IV, day 1 to day 4 Pegaspargase, 2000IU/m2/d IM, day 4<br>* Other names: Gemcitabine, Etoposide, Dexamethasone, Pegaspargase;Radiation: Radiotherapy<br>* Radiotherapy: 50-56Gy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate | The complete response rate will be assessed on day 28 after the 4th course of chemotherapy. | 28 days after 4 cycles of chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | Progression free survival is the time from entry onto the treatment until lymphoma progression or death of any reason. | 2-year | 
| Overall Response rate | The complete response rate will be assessed on day 28 after the 4th course of chemotherapy. | 28 days after 4 cycles of chemotherapy | 
| Treatment-Related Adverse Events as Assessed by CTCAE v4.0 | Treatment-Related Adverse Events will be assessed and graded by NCI CTCAE v4.0. | Day 1 of each course and then every 3 months for 2 years | 
| Overall survival | Overall survival is defiend as the time from entry onto the treatment until death of any reason | 2-year |