Clinical trial NCT01991158: GAD-M Regimen As First-Line Treatment in Untreated Extranodal NK/T Cell Lymphoma
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Extranodal NK/T-cell Lymphoma, Nasal Type
Keywords: GAD-M regimen
first line chemotherapy
NK/T-cell Lymphoma
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: Eli Lilly and Company
First posted: 2013-11-25
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: every 6 weeks, up to completion of treatment (approximately 6 months)
Secondary outcomes:
measure: Progress Free Survival (PFS)
timeFrame: up to end of follow-up-phase (approximately 5 years)
measure: Overall Survival (OS)
timeFrame: up to the date of death (approximately 5 years)
Other outcomes:
measure: The number of participants with adverse events of grade 3-4
timeFrame: every 3 weeks, up to completion of treatment (approximately 6 months)
measure: Epstein-Barr virus(EBV) DNA copies and antibodies
timeFrame: every 3 weeks,up to completion of treatment(approximately 6 months)
measure: Plasma β2-microglobulin
timeFrame: every 3 weeks,up to completion of treatment(approximately 6 months)
measure: Urinary microglobulin β2
timeFrame: every 3 weeks,up to completion of treatment(approximately 6 months)
measure: lymphocyte count
timeFrame: every 3 weeks,up to completion of treatment(approximately 6 months) 21
measure: Monocyte Count
timeFrame: every 3 weeks,up to completion of treatment(approximately 6 months)
measure: C reactive protein
timeFrame: every 3 weeks,up to completion of treatment(approximately 6 months)
Locations:
city: Guangzhou
country: China
facility: Department of Medical Oncology, Sun Yat-Sen University Cancer Center
state: Guangdong
Study officials:
affiliation: 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
name: Wenqi Jiang, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wang Y, Wang CQ, Sun P, Liu PP, Yang H, Wang HY, Rao HL, Li S, Jiang WQ, Huang JJ, Li ZM. Phase II Study of Gemcitabine, Peg-Asparaginase, Dexamethasone and Methotrexate Regimen for Newly Diagnosed Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type: Final Analysis With Long-Term Follow-Up and Rational Research for the Combination. Front Oncol. 2022 Jan 24;12:796738. doi: 10.3389/fonc.2022.796738. eCollection 2022.