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Efficacy and Safety Study of P-Gemox vs.EPOCH as First-line Chemotherapy to Treat NK/T-cell Lymphoma With Early Stage

Primary Purpose

Lymphoma, Extranodal NK-T-Cell

Status
Terminated
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Gemcitabine
Oxaliplatin
Pegaspargase
Etoposide
Vincristine
Doxorubicin
Cyclophosphamide
Prednisone
IMRT
Sponsored by
Sun Yat-sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma, Extranodal NK-T-Cell focused on measuring NK/T-cell lymphoma, induction chemotherapy, survival

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • newly diagnosed ENKTL
  • age:18-69years
  • Ann Arbor stage IE,or stage IIE with cervical lymph node involvement
  • at lease one measurable lesion
  • receive no chemotherapy or radiotherapy before
  • Eastern CooperativeOncology Group performance status of 0 to 2.
  • Adequate hematologic function (eg, white blood cell ≥ 3×10e9/l,neutrophils count ≥1.5×10e9/L, and platelet count≥ 100×10e9/L),renal function (eg, serum creatinine≤1.5 mg/dL and creatinine clearance ≥50 mL minute), and hepatic function (e.g, total bilirubin≤ 2 times the upper limit of normal and aspartate and alanine transaminase levels ≤ 3 times the upper limit of normal)

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

Sites / Locations

  • Sun Yat-sen University Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

P-Gemox

EPOCH

Arm Description

P-Gemox:gemcitabine :1250mg/m2 (ivdrip) on days 1, oxaliplatin :85 mg/m2 (ivdrip) on day 1, and pegaspargase : 2500 IU/m2 (intramuscular injection) on day 1.Cycle is repeated every 14 days. IMRT:IMRT is delivered using 6-8 MeV linear accelerator using intensity-modulated radiation treatment planning. The radiation dose is 50 grays (Gy) in 25 fractions.

EPOCH:Patients received the EPOCH chemotherapy regimen every 3 weeks. The EPOCH regimen included a 24 h continuous infusion of etoposide (50 mg/m 2 /day), vincristine (0.4 mg/m 2 /day) and doxorubicin(10 mg/m 2 /day administered on days 1-4, followed by cyclophosphamide (750 mg/m2 /day) over 15 min intravenously on day 5 and prednisone (60 mg/m 2 /day) on days1- 5 orally. IMRT:IMRT is delivered using 6-8 MeV linear accelerator using intensity-modulated radiation treatment planning. The radiation dose is 50 grays (Gy) in 25 fractions.

Outcomes

Primary Outcome Measures

progression free survival
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

Secondary Outcome Measures

complete remission rate
The criteria for the efficacy evaluation (overall response rate and complete remission) of the regimen is according to the following article: Cheson BD, Horning SJ, Coiffier B, et al. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999;17:1244.
overall survival
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
safety, as measured by adverse events
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)

Full Information

First Posted
February 4, 2015
Last Updated
May 8, 2018
Sponsor
Sun Yat-sen University
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1. Study Identification

Unique Protocol Identification Number
NCT02359162
Brief Title
Efficacy and Safety Study of P-Gemox vs.EPOCH as First-line Chemotherapy to Treat NK/T-cell Lymphoma With Early Stage
Official Title
Comparison of Gemcitabine, Oxaliplatin and Pegaspargase and Etoposide, Vincristine, Doxorubicin, Cyclophosphamide and Prednisone as First-line Chemotherapy in Patients With NK/T-cell Lymphoma:a Prospective Randomized Phase III Study
Study Type
Interventional

2. Study Status

Record Verification Date
October 2017
Overall Recruitment Status
Terminated
Why Stopped
The study is out of date
Study Start Date
May 2015 (undefined)
Primary Completion Date
June 2017 (Actual)
Study Completion Date
June 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Purpose :To compare the efficacy and and safety of the P-Gemox chemotherapy regimen with those of the EPOCH regimen for stage IE to IIE ENKTL.
Detailed Description
ENKTL is an aggressive type of NHL characterized by poor survival, for which the optimal treatment strategies have not been fully defined. Radiation therapy (RT) is widely administered for patients with localized nasal disease, and produces a complete response (CR) rate of up to 70%.However, local and systemic failures are observed frequently in patients who receive RT alone.Therefore, chemotherapy is needed in combination with RT to reduce the risk of recurrence. Unfortunately, ENKTL shows a poor response to the CHOP chemotherapy regimen (cyclophosphamide, doxorubicin, vincristine and prednisone) . EPOCH (etoposide, vincristine, doxorubicin, cyclophosphamide and prednisone) chemotherapy followed by involved field radiotherapy (IFRT) results in a CR rate of 75.0%. Recently, a chemotherapy regimen including gemcitabine,oxaliplatin and l-asparaginase (GELOX) has emerged, with promising results.Since 2003, a proportion of patients newly diagnosed with ENKTL were treated with the EPOCH chemotherapy regimen at some hospitals in China. From 2008, many hospitals in the southern part of China began to use the GELOX( Pegaspargase is used instead of l-asparaginase,P-Gemox).Our multicenter retrospective study showed the GELOX regimen produces a better long outcome with less toxicity than the EPOCH regimen for patients with early stage ENKTL.However,further prospective randomized clinical trials are needed to confirm the conclusion. Patients All patients should sign a written informed consent form before enrollment, and the study should be approved by the Sun Yat-sen University Cancer Center Ethics Board. Baseline of patients: Computed tomography (CT) scans of the chest, abdomen, and pelvis, magnetic resonance imaging studies of the head and neck, and bilateral bone marrow aspiration or biopsy. Positron emission tomography-CT scans (optional). Epstein-Barr virus (E B V) DNA blood levels, titer of EBV antibody (EA-IgA, VCA-IgA), β2-micro globulin (β2-MG) , IL-9 and IL-15 in the serum. Recheck before and after every course: Epstein-Barr virus (EBV) DNA blood levels, titer of EBV antibody (EA-IgA, VCA-IgA), β2-micro globulin (β2-MG), IL-9 and IL-15 in the serum. Recheck every two course: Computed tomography (CT) scans of the chest, abdomen, and pelvis, magnetic resonance imaging studies of the head and neck, and bilateral bone marrow aspiration or biopsy. Positron emission tomography-CT scans (optional) Treatment Protocol: The GELOX regimen consist of the following drugs: gemcitabine :1250 mg/ m2 on days 1,ivdrip oxaliplatin :85 mg/m2 on day 1, ivdrip pegaspargase : 2500 IU/m 2 daily on day 1,intramuscular. The treatment cycle is repeated every 14 days. The EPOCH regimen included a 24 h continuous infusion of etoposide (50 mg/m 2 /day), vincristine (0.4 mg/m 2 /day) and doxorubicin(10 mg/m 2 /day administered on days 1-4, followed by cyclophosphamide (750 mg/m2 /day) over 15 min intravenously on day 5 and prednisone (60 mg/m 2 /day) 60 mg/m 2 /day on days 1-5.The treatment cycle is repeated every 21 days. After at least two cycles of chemotherapy, patients who have achieved stable disease (SD) following two cycles, partial response (PR) after four cycles or complete response (CR) after six cycles of chemotherapy are referred to primary IFRT. ◦IFRT was delivered using 6-MeV linear accelerator using 3-dimensional conformable treatment planning. The IFRT dose was 56 grays (Gy) in 28 fractions, we define the clinical target volume of limited stage IE disease as the bilateral nasal cavity, bilateral ethmoid sinuses, and ipsilateral maxillary sinus; and the clinical target volume would extend to involved tissues for patients who had extensive stage IE disease. For patients who had stage IIE disease, the clinical target volume also, included the bilateral cervical lymph node area.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, Extranodal NK-T-Cell
Keywords
NK/T-cell lymphoma, induction chemotherapy, survival

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
P-Gemox
Arm Type
Experimental
Arm Description
P-Gemox:gemcitabine :1250mg/m2 (ivdrip) on days 1, oxaliplatin :85 mg/m2 (ivdrip) on day 1, and pegaspargase : 2500 IU/m2 (intramuscular injection) on day 1.Cycle is repeated every 14 days. IMRT:IMRT is delivered using 6-8 MeV linear accelerator using intensity-modulated radiation treatment planning. The radiation dose is 50 grays (Gy) in 25 fractions.
Arm Title
EPOCH
Arm Type
Active Comparator
Arm Description
EPOCH:Patients received the EPOCH chemotherapy regimen every 3 weeks. The EPOCH regimen included a 24 h continuous infusion of etoposide (50 mg/m 2 /day), vincristine (0.4 mg/m 2 /day) and doxorubicin(10 mg/m 2 /day administered on days 1-4, followed by cyclophosphamide (750 mg/m2 /day) over 15 min intravenously on day 5 and prednisone (60 mg/m 2 /day) on days1- 5 orally. IMRT:IMRT is delivered using 6-8 MeV linear accelerator using intensity-modulated radiation treatment planning. The radiation dose is 50 grays (Gy) in 25 fractions.
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Description
gemcitabine :1250mg/m2 (ivdrip) on days 1
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Intervention Description
oxaliplatin :85 mg/m2 (ivdrip) on day 1
Intervention Type
Drug
Intervention Name(s)
Pegaspargase
Intervention Description
pegaspargase : 2500 IU/m2 (intramuscular injection)
Intervention Type
Drug
Intervention Name(s)
Etoposide
Intervention Description
50 mg/m 2 /day 24 h continuous infusion on days 1-4
Intervention Type
Drug
Intervention Name(s)
Vincristine
Intervention Description
0.4 mg/m 2 /day 24 h continuous infusion on days 1-4
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Intervention Description
10 mg/m 2 /day 24 h continuous infusion on days 1-4
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
cyclophosphamide 750 mg/m2 /day over 15 min intravenously on day 5
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
60 mg/m 2 /day 60 mg/m 2 /day on days 1-5
Intervention Type
Radiation
Intervention Name(s)
IMRT
Other Intervention Name(s)
Intensity-modulated radiation therapy
Intervention Description
IMRT is delivered using 6-8 MeV linear accelerator using intensity-modulated radiation treatment planning. The radiation dose is 50 grays (Gy) in 25 fractions.
Primary Outcome Measure Information:
Title
progression free survival
Description
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
Time Frame
up to end of follow-up-phase (approximately 3 years)
Secondary Outcome Measure Information:
Title
complete remission rate
Description
The criteria for the efficacy evaluation (overall response rate and complete remission) of the regimen is according to the following article: Cheson BD, Horning SJ, Coiffier B, et al. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999;17:1244.
Time Frame
every 4 weeks,up to completion of treatment(approximately 6 months)
Title
overall survival
Description
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
Time Frame
.up to end of follow-up-phase (approximately 3 years)
Title
safety, as measured by adverse events
Description
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)
Time Frame
up to end of follow-up-phase (approximately 3 years)
Other Pre-specified Outcome Measures:
Title
serum Epstein-Barr virus(EBV) DNA copies
Time Frame
every 3 weeks,up to completion of treatment(approximately 6 months)
Title
serum β2-microglobulin
Time Frame
every 3 weeks,up to completion of treatment(approximately 6 months)
Title
serum interleukin 9
Time Frame
every 3 weeks,up to completion of treatment(approximately 6 months)
Title
serum interleukin 15
Time Frame
every 3 weeks,up to completion of treatment(approximately 6 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: newly diagnosed ENKTL age:18-69years Ann Arbor stage IE,or stage IIE with cervical lymph node involvement at lease one measurable lesion receive no chemotherapy or radiotherapy before Eastern CooperativeOncology Group performance status of 0 to 2. Adequate hematologic function (eg, white blood cell ≥ 3×10e9/l,neutrophils count ≥1.5×10e9/L, and platelet count≥ 100×10e9/L),renal function (eg, serum creatinine≤1.5 mg/dL and creatinine clearance ≥50 mL minute), and hepatic function (e.g, total bilirubin≤ 2 times the upper limit of normal and aspartate and alanine transaminase levels ≤ 3 times the upper limit of normal) 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hua Wang, MD.
Organizational Affiliation
Department of Hematological Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sun Yat-sen University Cancer Center
City
GuangZhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China

12. IPD Sharing Statement

Citations:
PubMed Identifier
24991715
Citation
Wang H, Wuxiao ZJ, Zhu J, Wang Z, Wang KF, Li S, Chen X, Lu Y, Xia ZJ. Comparison of gemcitabine, oxaliplatin and L-asparaginase and etoposide, vincristine, doxorubicin, cyclophosphamide and prednisone as first-line chemotherapy in patients with stage IE to IIE extranodal natural killer/T-cell lymphoma: a multicenter retrospective study. Leuk Lymphoma. 2015 Apr;56(4):971-7. doi: 10.3109/10428194.2014.939964. Epub 2014 Aug 20.
Results Reference
result
PubMed Identifier
22811078
Citation
Wang L, Wang ZH, Chen XQ, Li YJ, Wang KF, Xia YF, Xia ZJ. First-line combination of gemcitabine, oxaliplatin, and L-asparaginase (GELOX) followed by involved-field radiation therapy for patients with stage IE/IIE extranodal natural killer/T-cell lymphoma. Cancer. 2013 Jan 15;119(2):348-55. doi: 10.1002/cncr.27752. Epub 2012 Jul 18.
Results Reference
result
PubMed Identifier
21599590
Citation
Huang H, Lin Z, Lin X, Cai Q, Xia Z, Jiang W. Long-term outcomes of patients with newly diagnosed extranodal natural killer/T-cell lymphoma treated by etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin regimen: a single-institution experience. Leuk Lymphoma. 2011 Jun;52(6):1041-8. doi: 10.3109/10428194.2011.561388.
Results Reference
result
Links:
URL
http://www.nlm.nih.gov/medlineplus/
Description
medlineplus
URL
http://druginfo.nlm.nih.gov/drugportal/drugportal.jsp
Description
drug imformation

Learn more about this trial

Efficacy and Safety Study of P-Gemox vs.EPOCH as First-line Chemotherapy to Treat NK/T-cell Lymphoma With Early Stage

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