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

Sponsor

Huiqiang Huang (Other)

Overall Status

Recruiting

CT.gov ID

NCT02085655

Collaborator

Sun Yat-sen University (Other)

264

Enrollment

Location

Arms

116.2

Anticipated Duration (Months)

2.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Extranodal NK-T-Cell Lymphoma, Nasal and Nasal-Type	Drug: pegaspargase Drug: Gemcitabine Drug: Oxaliplatin Drug: Methotrexate Drug: Dexamethasone Drug: Thalidomide	Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

264 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 25, 2013

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Dec 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PEG-ASP+Gemox regimen group 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 pegaspargase: 2000U/m2 im on day 1 of each 21 day cycle. Number of Cycles: until progression or unacceptable toxicity develops. Other Names: Oncaspar Drug: Gemcitabine 1000mg/m2, ivd on day 1 and 8 of each 21 day cycle. Number of Cycles: until progression or unacceptable toxicity develops. Other Names: Gemzar Drug: Oxaliplatin 100mg/m2 ivd on day 1 of each 21 day cycle. Number of Cycles: until progression or unacceptable toxicity develops Other Names: Eloxatin Drug: Thalidomide 100-200mg, PO, after chemotherapy
Active Comparator: AspaMetDex regimen group 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 pegaspargase: 2000U/m2 im on day 1 of each 21 day cycle. Number of Cycles: until progression or unacceptable toxicity develops. Other Names: Oncaspar Drug: Methotrexate 3000m g/m2 civ 6-hour on day 1 of each 21 day cycle. Number of Cycles: until progression or unacceptable toxicity develops. Drug: Dexamethasone 40mg ivd on day 1 of each 21 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.

Arm

Intervention/Treatment

Experimental: PEG-ASP+Gemox regimen group

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

pegaspargase: 2000U/m2 im on day 1 of each 21 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.

Other Names:

Oncaspar

Drug: Gemcitabine

1000mg/m2, ivd on day 1 and 8 of each 21 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.

Other Names:

Gemzar

Drug: Oxaliplatin

100mg/m2 ivd on day 1 of each 21 day cycle. Number of Cycles: until progression or unacceptable toxicity develops

Other Names:

Eloxatin

Drug: Thalidomide

100-200mg, PO, after chemotherapy

Active Comparator: AspaMetDex regimen group

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

pegaspargase: 2000U/m2 im on day 1 of each 21 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.

Other Names:

Oncaspar

Drug: Methotrexate

3000m g/m2 civ 6-hour on day 1 of each 21 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.

Drug: Dexamethasone

40mg ivd on day 1 of each 21 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.

Outcome Measures

Primary Outcome Measures

Efficacy Outcome Measure [up to 24 months]
Study group increase 15% 2-year PFS

Secondary Outcome Measures

Safety/Adverse Event Outcome Measure [Up to 36 months]
Number of Participants with Serious and Non-Serious Adverse Events

Other Outcome Measures

Efficacy Outcome Measure [Up to 36 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.