PEG-ASP+Gemox Regimen and Thalidomide for NK/T Lymphoma

Study Overview
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Brief Summary
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Extranodal natural killer/T-cell lymphoma (ENKTL) is an aggressive form of non-Hodgkin's lymphoma and shows extremely poor survival. This prospective pilot study to evaluate the efficacy and safety of long-acting aspargase (pegylated aspargase, PEG-ASP) combined with gemcitabine and oxaliplatin (PASP -Gemox) treatment in this population.

Detailed Description
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Eligibility criteria The eligibility criteria were pathologically confirmed, previously untreated or refractory/relapsed ENKTL as defined by the World Health Organization classification; age≥18 years; Eastern Cooperative Oncology Group (ECOG) performance status of 0-2; at least one measurable lesion; adequate haematologic function (haemoglobin > 9.0 g/l, absolute neutrophil count > 1500/ml, platelets > 75,000/l), hepatic function (total serum bilirubin ≤ 1.5 times the upper limit of normal, alanine aminotransferase and aspartate aminotransferase ≤ 2.5 times the upper limit of normal), renal function (serum creatinine ≤ 1.5 mg/dl, creatinine clearance ≥ 50 ml/min); normal coagulation function and electrocardiogram results. Prior chemotherapy and radiotherapy should have been completed >4 weeks earlier, willingness to provide written informed consent. Stage was defined according to the Ann Arbor system. The Sun Yat-Sen University Cancer Centre Research Ethics Board approved this study before subjects were enrolled. Treatment PA-Gemox dosages were as follows: days 1 and 8, 30-min intravenous infusion of 1000 mg/m2 gemcitabine; day 1, 2-h intravenous infusion of 130 mg/m2 oxaliplatin; day 1, deep intramuscular injection of 2500 U/m2 PEG-ASP at two different sites. The regimen was repeated every 3 weeks for a maximum of six cycles. Stage IE/IIE patients underwent four cycles induction chemotherapy, followed by involved-field radiotherapy after got CR, PR or SD. Three-dimensional conformal radiotherapy was done by linear accelerator at 2.0 grays (Gy) per daily fraction with 5-6 weeks. The involved- field radiation (IFRT) dose was 50-56 Gy. Refractory/relapsed patients underwent at least two cycles treatments unless there was disease progression or unacceptable side effects, or withdrawal of patient consent. Autologous haematopoietic stem cell transplantation (AHSCT) was recommended after they achieved CR.

Official Title
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PA-Gemox Regimen Followed by Thalidomide Versus AspaMetDex Regimen in NKTCL Patients：a Randomized, Open-label, Phase 3 Study

Conditions
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Extranodal NK-T-Cell Lymphoma, Nasal and Nasal-Type

Intervention / Treatment
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* Drug: pegaspargase
* Drug: Gemcitabine
* Drug: Oxaliplatin
* Drug: Methotrexate
* Drug: Dexamethasone
* Drug: Thalidomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: pathologically confirmed, previously untreated or refractory/relapsed ENKTL as defined by the World Health Organization classification; age≥18 years; Eastern Cooperative Oncology Group (ECOG) performance status of 0-2; at least one measurable lesion; adequate haematologic function (haemoglobin > 9.0 g/l, absolute neutrophil count > 1500/ml, platelets > 75,000/l), adequate hepatic function (total serum bilirubin ≤ 1.5 times the upper limit of normal, alanine aminotransferase and aspartate aminotransferase ≤ 2.5 times the upper limit of normal), adequate renal function (serum creatinine ≤ 1.5 mg/dl, creatinine clearance ≥ 50 ml/min); normal coagulation function and electrocardiogram results. Prior chemotherapy and radiotherapy should have been completed >4 weeks earlier, willingness to provide written informed consent. Exclusion Criteria: -

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PEG-ASP+Gemox regimen group<br>PEG-ASP 2000U/m2 im d1 Gemcitabine 800mg/m2 ivdrip 30min d1，8 Oxaliplatin 100mg/m2 ivdrip d1 Thalidomide 150-200mg po qn d8-21 | Drug: pegaspargase<br>* pegaspargase: 2000U/m2 im on day 1 of each 21 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.<br>* Other names: Oncaspar;Drug: Gemcitabine<br>* 1000mg/m2, ivd on day 1 and 8 of each 21 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.<br>* Other names: Gemzar;Drug: Oxaliplatin<br>* 100mg/m2 ivd on day 1 of each 21 day cycle. Number of Cycles: until progression or unacceptable toxicity develops<br>* Other names: Eloxatin;Drug: Thalidomide<br>* 100-200mg, PO, after chemotherapy<br>|
| Active Comparator: AspaMetDex regimen group<br>Pegaspargase 2000U/m2 im， d1 methotrexate 3000m g/m2 civ 6-hour，d1, Calcium folinate 30mg iv q6h x6 Dexamethasone 40 mg ivdrip QD | Drug: pegaspargase<br>* pegaspargase: 2000U/m2 im on day 1 of each 21 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.<br>* Other names: Oncaspar;Drug: Methotrexate<br>* 3000m g/m2 civ 6-hour on day 1 of each 21 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.<br>Drug: Dexamethasone<br>* 40mg ivd on day 1 of each 21 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy Outcome Measure | Study group increase 15% 2-year PFS | up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety/Adverse Event Outcome Measure | Number of Participants with Serious and Non-Serious Adverse Events | Up to 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Extranodal NK/T-cell lymphoma, PA-Gemox regimen, thalidomide