MEDA Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation for Stage IV 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 methotrexate, etoposide, pegaspargase and dexamethasone (MEDA) chemotherapy and autologous hematopoietic stem cell transplantation (Auto-HSCT) in patients with stage IV 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. L-asparaginase based chemotherapy improved overall response and prolonged the long-term survival for patients with stage IV. But the optimal treatment schedule has not been established. This study is designed with four cycles MEDA chemotherapy, followed by Auto-HSCT for stage IV patients with newly onset, relapsed or refractory diseases. The efficacy and safety of this protocol in the treatment of will be measured.

Official Title
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The Efficacy and Safety of Methotrexate, Etoposide, Dexamethasone and Pegaspargase Chemotherapy (MEDA) With Autologous HSCT in the Treatment of Stage IV 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: MEDA
* Procedure: Auto-HSCT


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 based on WHO 2008 classification of tumors of haematopoietic and lymphoid tissue. Eastern Cooperative Oncology Group (ECOG ) performance status 0 3. Stage IV disease with at least one measurable lesion. Preserved organ functions for: Platelet>50×10*9/L, hemoglobin>80g/L, total bilirubin (TBIL)<3×ULN, alanine transaminase (ALT)<5×ULN, serum creatinine (Cr)<1.5×ULN, fibrinogen≥0.5g/L, LVEF≥50%. Signed Informed consented. Exclusion Criteria: Relapsed or progressive disease to prior L-asparaginase-based chemotherapy. Concurrent cancers need surgery or chemotherapy within 6 months. History of chemotherapy or radiotherapy for other solid cancers within 3 years. Recent history of radiotherapy of upper-aero-digestive tract within last 3 months. Significant complications: LVEF≤50%, coagulopathy, autoimmune disease, severe infection, or liver cirrhosis, severe hemophagocytic lymphohistiocytosis. Mental disorders. Pregnant or lactation. HIV, hepatitis virus C (HCV), or active hepatitis virus B (HBV) infection with HBV DNA≥10*5 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: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MEDA/Auto-HSCT<br>Patients will be initially treated with four cycles MEDA chemotherapy, followed by autologous hematopoietic stem cell transplantation (Auto-HSCT). | Drug: MEDA<br>* Methotrexate, 3.0g/m2/d iv, day 1 Etoposide, 100mg/m2 iv, day 2 to day 4 Dexamethasone, 40mg/d iv, day 1 to day 4 Pegaspargase, 2500IU/m2/d im, day 4 The MEDA chemotherapy will be repeated every 3 weeks.<br>* Other names: Methotrexate, Etoposide,Dexamethasone,Pegaspargase;Procedure: Auto-HSCT<br>* Auto-HSCT will be performed with patients who responded to the initial MEDA chemotherapy with standard BEAM conditioning regimen.<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 of the 4th course of MEDA chemotherapy. | Day 28 of the 4th course of MEDA 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 overall response rate will be assessed on day 28 of the 4th course of MEDA chemotherapy. | Day 28 of the 4th course of MEDA 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 of chemotherapy 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 |