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

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)

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.

Study Overview

• Status: Unknown
• Conditions: Extranodal NK/T-cell Lymphoma, Nasal Type
• Intervention / Treatment: Drug: Gemcitabine; Drug: Pegaspargase; Drug: Dexamethasone; Drug: High dose of methotrexate

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 Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Department of Medical Oncology, Sun Yat-Sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GAD-M regimen; GAD-M regimen means High dose of methotrexate combined with gemcitabine, pegaspargase and dexamethasone	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; Drug: High dose of methotrexate; Methotrexate 3.0g/Kg, intravenous drip D1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Measure Description	Time Frame
Monocyte Count	21 days(3 weeks) for one cycle	every 3 weeks,up to completion of treatment(approximately 6 months)
C reactive protein	21 days(3 weeks) for one cycle	every 3 weeks,up to completion of treatment(approximately 6 months)
Plasma β2-microglobulin	21 days(3 weeks) for one cycle	every 3 weeks,up to completion of treatment(approximately 6 months)
Urinary microglobulin β2	21 days(3 weeks) for one cycle	every 3 weeks,up to completion of treatment(approximately 6 months)
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)
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)
lymphocyte count	21 days(3 weeks) for one cycle	every 3 weeks,up to completion of treatment(approximately 6 months) 21

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: 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

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Anticipated): December 1, 2016
• Study Completion (Anticipated): November 1, 2020

Study Registration Dates

• First Submitted: November 7, 2013
• First Submitted That Met QC Criteria: November 17, 2013
• First Posted (Estimate): November 25, 2013

Study Record Updates

• Last Update Posted (Estimate): June 14, 2016
• Last Update Submitted That Met QC Criteria: June 11, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: first line chemotherapy; NK/T-cell Lymphoma; GAD-M regimen
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, Extranodal NK-T-Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Gemcitabine; Dexamethasone; Methotrexate; Pegaspargase
• Other Study ID Numbers: B2013-030-01