Concomitant Chemo-radiotherapy Plus VIDL Chemotherapy in NK/T-cell Lymphoma

Phase 2

Completed

Brief Summary: This study is to evaluate the efficacy of risk-adapted treatment strategy for stage I/II extranodal NK/T cell lymphoma. The risk stratification is based on the Korean NK prognostic index. Thus, the group I/II will receive concomitant chemoradiation followed by VIDL chemotherapy. The group III/IV will receive high dose-chemotherapy followed by autologous stem cell transplantation after the completion of VIDL chemotherapy.

Detailed Description: 1. Concomitant chemo-radiotherapy:

Radiotherapy 36-44 Gy/18-22 fractions

+ weekly cisplatin 30 mg/m2 for 4 weeks

2. Rest period: 3 weeks

3. VIDL combination chemotherapy: (total 2 cycles) VP-16 (etoposide) 100mg/m2 I.V. D1-3 Ifosfamide 1.2g/m2 I.V. D1-3 Dexamethasone 40mg/day D1-3 L-asparaginase 4000IU/m2 IM D8, 10, 12, 14, 16, 18, 20 Repeated every 28 days

4. Peripheral blood stem cell mobilization G-CSF 400ug/m2/day or 10ug/kg/day S.C. or I.V. for 4-6 days followed by stem cell collection (Minimum requirement of CD34+ cells \> 2×106/kg)

5. High-dose chemotherapy with autologous stem cell transplantation Busulfex 3.2mg/kg/day from day -7 to day -5 Etoposide 400mg/m2/day on day -5, -4 Cyclophosphamide 50mg/kg/day on day -3, -2 Followed by stem cell infusion

Recruitment & Eligibility

Inclusion Criteria

patients were required to have a biopsy-proven diagnosis of nasal ENKTL
at least 18 years old
Ann Arbor stage IE or IIE
measurable disease
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
life expectancy greater than 12 weeks
adequate hematologic (hemoglobin > 9.0 g/dL, absolute neutrophil count > 1,500/uL and platelets > 100,000/uL)
renal (serum creatinine < 1.5 mg/dL, creatinine clearance > 50 mL/min)
hepatic (total bilirubin < 2 times of upper limit of normal and aspartate transferase < 3 times of upper limit of normal) function
Diagnosis of ENKTL is based on the presence of histological features and immunophenotypes compatible with ENKTL (e.g., cytoplasmic CD3+, CD20-, CD56+, positive for cytotoxic molecules, positive for EBV by in situ hybridization).
Informed consent

Exclusion Criteria

prior or concomitant malignant tumors
any coexisting medical problems of sufficient severity to prevent full compliance with the study protocol.
ENKTL with non-nasal sites such as skin or gastrointestinal tract was excluded even if it is localized.
Other subtypes of non-Hodgkin lymphoma (NHL), including myeloid/NK cell precursor acute leukemia, blastic NK cell lymphoma/precursor NK cell lymphoblastic leukemia, aggressive NK cell leukemia, and peripheral T cell lymphoma, unspecified, were excluded.

Arm && Interventions

Group	Intervention	Description
CCRT plus VIDL	CCRT followed by VIDL chemotherapy	CCRT followed by VIDL chemotherapy Concomitant chemo-radiotherapy followed by VIDL chemotherapy with risk-based application of autologous stem cell transplantation Patients who are planned to be treated with CCRT plus VIDL chemotherapy and/or autologous stem cell transplantation

Primary Outcome Measures

Name	Time	Method
Compete Response Rate	Within 3 weeks after the completion fo treatment	Response was determined by the revised response criteria for malignant lymphoma (Cheson BD et al. J Clin Oncol. 2007 Feb 10;25(5):579-86.): 1) Complete response 2) Partial response 3) Stable disease 4) Progressive disease

Secondary Outcome Measures