PEG-ASP+Gemoxd vs. PEG-ASP+CHOP as First-line Chemotherapy to Treatment NK/T-cell Lymphoma With Early Stage

Sponsor

Hunan Cancer Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT02918747

Collaborator

(none)

100

Enrollment

Location

Arms

Duration (Months)

1.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Extranodal natural killer/T-cell lymphoma (ENKTL) is an aggressive subtype of non-Hodgkin's lymphoma and shows extremely poor survival. Several retrospective studies and singe-arm prospective phase 2 studies have shown that pegaspargase combined Gemox or CHOP regimen achieved a promising efficacy in treatment of ENKTL. However, there is no prospective study to compare the efficacy of these two regimens. This prospective pilot study to compare the efficacy and safety of the P-Gemoxd chemotherapy regimen with those of the P-CHOP regimen for stage IE to IIE ENKTL.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Drug: pegaspargase Drug: Gemcitabine Drug: Oxaliplatin Drug: Dexamethasone Drug: Cyclophosphamide Drug: Doxorubicin Drug: Vincristine Drug: Prednisone Radiation: IMRT	Phase 2

Detailed Description

Treatment PA-Gemoxd dosages were as follows: days 1 and 5, 30-min intravenous infusion of 800 mg/m2 gemcitabine; day 1, 2-h intravenous infusion of 85 mg/m2 oxaliplatin; day 1, deep intramuscular injection of 2000 U/m2 PEG-ASP at four different sites; d1-5, intravenous infusion of 15mg dexamethasone. The regimen was repeated every 3 weeks for four cycles 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

P-Gemoxd Regimen Followed by Radiotherapy Versus P-CHOP Regimen Followed by Radiotherapy in ENKTL With Early Stage: a Randomized, Multicenter, Open-label, Phase 2 Study

Study Start Date :

Sep 1, 2016

Anticipated Primary Completion Date :

Sep 1, 2021

Anticipated Study Completion Date :

Dec 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: P-Gemoxd Pegaspargase+Gemcitabine+Oxaliplatin+Dexamethasone (PEG-ASP+Gemoxd): Patients received the P-Gemoxd chemotherapy regimen every 3 weeks. Pegaspargase 2000U/m2 im day 1, Gemcitabine 800mg/m2 ivdrip 30min day 1 and day 5, Oxaliplatin 85mg/m2 ivdrip day 1, Dexamethasone 15 mg ivdrip, QD, day 1 to day 5. IMRT：IMRT is delivered using 6-8 MeV linear accelerator using intensity-modulated radiation treatment planning. The radiation dose is 50 -56grays (Gy) in 25-28 fractions.	Drug: pegaspargase P-Gemoxd Arm: 2000U/m2 im on day 1 of each 21 day cycle. Number of Cycles: four. P-CHOP Arm: 2000U/m2 im on day 2 of each 21 day cycle. Number of Cycles: four. Other Names: Oncaspar Drug: Gemcitabine 800mg/m2, ivd on day 1 and 5 of each 21 day cycle. Number of Cycles: four. Other Names: Gemzar Drug: Oxaliplatin 85 mg/m2 ivd on day 1 of each 21 day cycle. Number of Cycles: four Other Names: Eloxatin Drug: Dexamethasone 15 mg, Ivd on day 1 to day 5 of each 21 day cycle. Number of Cycles: four. Radiation: IMRT After chemotherapy, if the patients get CR, PR or SD, IMRT is delivered using 6-8 MeV linear accelerator using intensity-modulated radiation treatment planning. The radiation dose is 50 -56grays (Gy) in 25-28 fractions. Other Names: intensity-modulated radiation treatment
Active Comparator: P-CHOP Pegaspargase+Cyclophosphamide+Doxorubicin+Vincristine +Prednisone (P-CHOP)：Patients received the P-CHOP chemotherapy regimen every 3 weeks. Cyclophosphamide 750 mg/m2，ivdrip day 1； doxorubicin 50mg/m 2，ivdrip day 1；vincristine 1.4 mg/m 2(≤2mg），ivdrip day 1; Pegaspargase 2000U/m2 im，day 2 and prednisone (60 mg/m 2 /day) on days 1 to 5 orally. IMRT is delivered using 6-8 MeV linear accelerator using intensity-modulated radiation treatment planning. The radiation dose is 50-56 grays (Gy) in 25-28 fractions.	Drug: pegaspargase P-Gemoxd Arm: 2000U/m2 im on day 1 of each 21 day cycle. Number of Cycles: four. P-CHOP Arm: 2000U/m2 im on day 2 of each 21 day cycle. Number of Cycles: four. Other Names: Oncaspar Drug: Cyclophosphamide 750 mg/m2，ivdrip day 1 of each 21 day cycle. Number of Cycles: four. Drug: Doxorubicin 50mg/m 2，ivdrip day 1 of each 21 day cycle. Number of Cycles: four. Drug: Vincristine 1.4 mg/m 2(≤2mg），ivdrip day 1 of each 21 day cycle. Number of Cycles: four. Drug: Prednisone 60 mg/m 2 /day orally on days1- 5 of each 21 day cycle. Number of Cycles: four. Radiation: IMRT After chemotherapy, if the patients get CR, PR or SD, IMRT is delivered using 6-8 MeV linear accelerator using intensity-modulated radiation treatment planning. The radiation dose is 50 -56grays (Gy) in 25-28 fractions. Other Names: intensity-modulated radiation treatment

Arm

Intervention/Treatment

Experimental: P-Gemoxd

Pegaspargase+Gemcitabine+Oxaliplatin+Dexamethasone (PEG-ASP+Gemoxd): Patients received the P-Gemoxd chemotherapy regimen every 3 weeks. Pegaspargase 2000U/m2 im day 1, Gemcitabine 800mg/m2 ivdrip 30min day 1 and day 5, Oxaliplatin 85mg/m2 ivdrip day 1, Dexamethasone 15 mg ivdrip, QD, day 1 to day 5. IMRT：IMRT is delivered using 6-8 MeV linear accelerator using intensity-modulated radiation treatment planning. The radiation dose is 50 -56grays (Gy) in 25-28 fractions.

Drug: pegaspargase

P-Gemoxd Arm: 2000U/m2 im on day 1 of each 21 day cycle. Number of Cycles: four. P-CHOP Arm: 2000U/m2 im on day 2 of each 21 day cycle. Number of Cycles: four.

Other Names:

Oncaspar

Drug: Gemcitabine

800mg/m2, ivd on day 1 and 5 of each 21 day cycle. Number of Cycles: four.

Other Names:

Gemzar

Drug: Oxaliplatin

85 mg/m2 ivd on day 1 of each 21 day cycle. Number of Cycles: four

Other Names:

Eloxatin

Drug: Dexamethasone

15 mg, Ivd on day 1 to day 5 of each 21 day cycle. Number of Cycles: four.

Radiation: IMRT

After chemotherapy, if the patients get CR, PR or SD, IMRT is delivered using 6-8 MeV linear accelerator using intensity-modulated radiation treatment planning. The radiation dose is 50 -56grays (Gy) in 25-28 fractions.

Other Names:

intensity-modulated radiation treatment

Active Comparator: P-CHOP

Pegaspargase+Cyclophosphamide+Doxorubicin+Vincristine +Prednisone (P-CHOP)：Patients received the P-CHOP chemotherapy regimen every 3 weeks. Cyclophosphamide 750 mg/m2，ivdrip day 1； doxorubicin 50mg/m 2，ivdrip day 1；vincristine 1.4 mg/m 2(≤2mg），ivdrip day 1; Pegaspargase 2000U/m2 im，day 2 and prednisone (60 mg/m 2 /day) on days 1 to 5 orally. IMRT is delivered using 6-8 MeV linear accelerator using intensity-modulated radiation treatment planning. The radiation dose is 50-56 grays (Gy) in 25-28 fractions.

Drug: pegaspargase

P-Gemoxd Arm: 2000U/m2 im on day 1 of each 21 day cycle. Number of Cycles: four. P-CHOP Arm: 2000U/m2 im on day 2 of each 21 day cycle. Number of Cycles: four.

Other Names:

Oncaspar

Drug: Cyclophosphamide

750 mg/m2，ivdrip day 1 of each 21 day cycle. Number of Cycles: four.

Drug: Doxorubicin

50mg/m 2，ivdrip day 1 of each 21 day cycle. Number of Cycles: four.

Drug: Vincristine

1.4 mg/m 2(≤2mg），ivdrip day 1 of each 21 day cycle. Number of Cycles: four.

Drug: Prednisone

60 mg/m 2 /day orally on days1- 5 of each 21 day cycle. Number of Cycles: four.

Radiation: IMRT

Other Names:

intensity-modulated radiation treatment

Outcome Measures

Primary Outcome Measures

Objective response rate（complete remission rate + partial remission rate） [every 6 weeks,up to completion of treatment (approximately 6 months)]
The criteria for the efficacy evaluation (overall response rate and complete remission) of the regimen is according to the following article: Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014 Sep 20;32(27):3059-68.
progression free survival [up to end of follow-up-phase (approximately 3 years)]
time from the date of enrollment to date of disease progression, or death of any cause, or date of lost follow-up, whichever comes first
overall survival [up to end of follow-up-phase (approximately 3 years)]
overall survival (OS): time from the date of enrollment to date of death from any cause, or date of lost follow-up, whichever comes first

Secondary Outcome Measures

Incidence of Treatment-Emergent Adverse Events according to Common Terminology Criteria for Adverse Events v3.0 [every 3 weeks,up to completion of treatment (approximately 6 months)]
including hematological safety and non-hematological safety. All the adverse events will be classified according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE)

Other Outcome Measures

Serum Epstein-Barr virus (EBV) DNA copies [every 3 weeks,up to completion of treatment (approximately 6 months)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

pathologically confirmed, previously untreated ENKTL with stage I/II (for stage I, the patients should have one of the following risk factors: EBV-DNA > upper limit of normal, lesions beyond nasal, fever, LDH elevation);
age range from 18 to 70 years;
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
at least one measurable lesion;
adequate haematologic function (haemoglobin > 8.0 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),
Hepatitis B virus carriers should have normal HBV-DNA copies and should use antiviral drugs. For patients with elevated HBV-DNA, should use antiviral drugs until the HBV-DNA decrease to < 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:

mismatch the inclusion criteria
systematic central nervous system involvement, previous or concomitant malignancies and any coexisting medical problems that could cause poor compliance with the study protocol.
primary lesion not from the upper respiratory