GAD-M Regimen As First-Line Treatment in Untreated Extranodal NK/T Cell Lymphoma

Sponsor

Sun Yat-sen University (Other)

Overall Status

Unknown status

CT.gov ID

NCT01991158

Collaborator

Eli Lilly and Company (Industry)

Enrollment

Location

Arm

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of High dose of Methotrexate combined with gemcitabine, pegaspargase and dexamethasone (GAD-M regimen) as first-line treatment in patients with de novo extranodal NK/T cell lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Extranodal NK/T-cell Lymphoma, Nasal Type	Drug: High dose of methotrexate Drug: Gemcitabine Drug: Pegaspargase Drug: Dexamethasone	Phase 2

Detailed Description

Studies have shown that effects of P glycoprotein mediated chemotherapy resistance reduce the therapeutic efficacy of anthracycline-based chemotherapy of NK/T cell lymphoma, and agents like pegaspargase and large doses of Methotrexate is not affected by the P glycoprotein. A number of reports suggest that gemcitabine combined with other chemotherapy drugs has good application prospect in the treatment of lymphomas. Dexamethasone is used in combination with other agents for the treatment of lymphomas which may be implicated in the development or growth of some cancers. So we explored to evaluate the efficacy and safety of High dose of methotrexate combined with gemcitabine, pegaspargase and dexamethasone (GAD-M regimen) as first-line treatment in patients with untreated extranodal NK/T cell lymphoma.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open, Single-center, Phase II Clinical Trial for Treatment of Untreated Extranodal NK/T Cell Lymphoma With High Dose of Methotrexate in Combination With Gemcitabine, Pegaspargase and Dexamethasone (GAD-M Regimen)

Study Start Date :

Nov 1, 2013

Anticipated Primary Completion Date :

Dec 1, 2016

Anticipated Study Completion Date :

Nov 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GAD-M regimen GAD-M regimen means High dose of methotrexate combined with gemcitabine, pegaspargase and dexamethasone	Drug: High dose of methotrexate Methotrexate 3.0g/Kg, intravenous drip D1 Drug: Gemcitabine Gemcitabine 1g/m2 intravenous drip D1,D8 Drug: Pegaspargase Pegaspargase 2500U/m2 intramuscular injection (IM) D1 Drug: Dexamethasone Dexamethasone 20mg/d intravenous drip D1, po D2-3

Arm

Intervention/Treatment

Experimental: GAD-M regimen

GAD-M regimen means High dose of methotrexate combined with gemcitabine, pegaspargase and dexamethasone

Drug: High dose of methotrexate

Methotrexate 3.0g/Kg, intravenous drip D1

Drug: Gemcitabine

Gemcitabine 1g/m2 intravenous drip D1,D8

Drug: Pegaspargase

Pegaspargase 2500U/m2 intramuscular injection (IM) D1

Drug: Dexamethasone

Dexamethasone 20mg/d intravenous drip D1, po D2-3

Outcome Measures

Primary Outcome Measures

Overall Response Rate (ORR) [every 6 weeks, up to completion of treatment (approximately 6 months)]
21 days (3 weeks) for one cycle, Efficacy was evaluated every two cycles

Secondary Outcome Measures

Progress Free Survival (PFS) [up to end of follow-up-phase (approximately 5 years)]
Overall Survival (OS) [up to the date of death (approximately 5 years)]

Other Outcome Measures

The number of participants with adverse events of grade 3-4 [every 3 weeks, up to completion of treatment (approximately 6 months)]
21 days (3 weeks) for one cycle, Toxicity was evaluated every cycle
Epstein-Barr virus(EBV) DNA copies and antibodies [every 3 weeks,up to completion of treatment(approximately 6 months)]
21 days(3 weeks) for one cycle
Plasma β2-microglobulin [every 3 weeks,up to completion of treatment(approximately 6 months)]
21 days(3 weeks) for one cycle
Urinary microglobulin β2 [every 3 weeks,up to completion of treatment(approximately 6 months)]
21 days(3 weeks) for one cycle
lymphocyte count [every 3 weeks,up to completion of treatment(approximately 6 months) 21]
21 days(3 weeks) for one cycle
Monocyte Count [every 3 weeks,up to completion of treatment(approximately 6 months)]
21 days(3 weeks) for one cycle
C reactive protein [every 3 weeks,up to completion of treatment(approximately 6 months)]
21 days(3 weeks) for one cycle

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologic diagnosis of NK/T Cell Lymphoma;
Age:18-80 years;
Weight：Male：67±20Kg（47-87Kg），Female：55±20Kg（35-75Kg）
Eastern Cooperative Oncology Group (ECOG) status 0-3, Estimated survival time > 3 months;
No history of other malignancies; No other current tumors；
Normal haematological, liver and renal function (WBC count≥3.5×109/L, Hemoglobin≥100g/L, platelet count≥90×109/L, bilirubin<1.5×ULN, Alanine transaminase (ALT) and Aspartate Aminotransferase (AST)<2.5×ULN, serum creatinine<1.5×ULN), normal coagulation function and cardiac function;
Clinical staging I-IV；
No previous treatments including chemotherapy, radiotherapy, targeted therapy or stem cell transplantation;
Appreciable and measurable lesions, clinical assessment >2cm，CT or MRI >1.5cm;
No other serious diseases which conflict with the treatment in the present trial;
No concurrent treatments that conflict with the treatments in the present trial(including steroid drugs);
Voluntary participation and signed the informed consent.

Exclusion Criteria:

The patients had the conditions below: clinically significant ventricular tachycardia (VT), atrial fibrillation (AF), heart block, myocardial infarction (MI), congestive heart failure (CHF), symptomatic coronary artery heart disease requiring medication;
The patients suffered from organ transplant
The patients participated in other clinical trials within the 30 days before enrollment or who are participating in other clinical studies;
The patients with active bleeding or new thrombotic disease, who are taking anticoagulant drugs or with a history of bleeding tendencies，who with active infection;
The patients suffered before surgery less than four weeks, or after less than six weeks;
The patients with abnormal liver function (total bilirubin> 1.5 times the normal value, ALT / AST> 2.5 times normal), abnormal renal function (serum creatinine> 1.5 times normal), blood abnormalities (absolute neutrophil count <1.5 × 109 / L, platelets <80 × 109 / L, hemoglobin <90g /L) ;
The patients with mentally ill / unable to obtain informed consent;
The patients with drug addiction, alcohol abuse which affects the long-term evaluation of test results;
The patients in pregnancy, lactation and women of childbearing age who do not want to take contraceptive measures subjects;
Clinical and laboratory support brain metastases;
The patients with a history of allergy or adverse reaction(s) to test drug;
The patients not suitable to participate in the investigator judged by researchers.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Medical Oncology, Sun Yat-Sen University Cancer Center	Guangzhou	Guangdong	China	510060

Sponsors and Collaborators

Sun Yat-sen University
Eli Lilly and Company

Investigators

Principal Investigator: Wenqi Jiang, MD, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China