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

Extranodal NK/T-cell Lymphoma, Nasal Type Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01991158
• Other study ID #: B2013-030-01
• Status: Active, not recruiting
• Phase: Phase 2
• First received: November 7, 2013
• Last updated: June 11, 2016
• Start date: November 2013
• Est. completion date: November 2020

Study information

• Verified date: June 2016
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 30
• Est. completion date: November 2020
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Extranodal NK/T-cell Lymphoma, Nasal Type
• Lymphoma
• Lymphoma, Extranodal NK-T-Cell
• Lymphoma, T-Cell

Intervention

Drug:
• High dose of methotrexate
Methotrexate 3.0g/Kg, intravenous drip D1
• Gemcitabine
Gemcitabine 1g/m2 intravenous drip D1,D8
• Pegaspargase
Pegaspargase 2500U/m2 intramuscular injection (IM) D1
• Dexamethasone
Dexamethasone 20mg/d intravenous drip D1, po D2-3

Locations

Country	Name	City	State
China	Department of Medical Oncology, Sun Yat-Sen University Cancer Center	Guangzhou	Guangdong

Sponsors (2)

Lead Sponsor	Collaborator
Sun Yat-sen University	Eli Lilly and Company

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	The number of participants with adverse events of grade 3-4	21 days (3 weeks) for one cycle, Toxicity was evaluated every cycle	every 3 weeks, up to completion of treatment (approximately 6 months)	Yes
Other	Epstein-Barr virus(EBV) DNA copies and antibodies	21 days(3 weeks) for one cycle	every 3 weeks,up to completion of treatment(approximately 6 months)	No
Other	Plasma ß2-microglobulin	21 days(3 weeks) for one cycle	every 3 weeks,up to completion of treatment(approximately 6 months)	No
Other	Urinary microglobulin ß2	21 days(3 weeks) for one cycle	every 3 weeks,up to completion of treatment(approximately 6 months)	No
Other	lymphocyte count	21 days(3 weeks) for one cycle	every 3 weeks,up to completion of treatment(approximately 6 months) 21	No
Other	Monocyte Count	21 days(3 weeks) for one cycle	every 3 weeks,up to completion of treatment(approximately 6 months)	No
Other	C reactive protein	21 days(3 weeks) for one cycle	every 3 weeks,up to completion of treatment(approximately 6 months)	No
Primary	Overall Response Rate (ORR)	21 days (3 weeks) for one cycle, Efficacy was evaluated every two cycles	every 6 weeks, up to completion of treatment (approximately 6 months)	No
Secondary	Progress Free Survival (PFS)		up to end of follow-up-phase (approximately 5 years)	No
Secondary	Overall Survival (OS)		up to the date of death (approximately 5 years)	No