MEDA Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation for Stage IV Natural Killer/T-cell Lymphoma

The Efficacy and Safety of Methotrexate, Etoposide, Dexamethasone and Pegaspargase Chemotherapy (MEDA) With Autologous HSCT in the Treatment of Stage IV Natural Killer/T-Cell Lymphoma: A Multicenter, Prospective Study

The purpose of this study is to evaluate the efficacy and safety of methotrexate, etoposide, pegaspargase and dexamethasone (MEDA) chemotherapy and autologous hematopoietic stem cell transplantation (Auto-HSCT) in patients with stage IV extranodal natural killer/T-cell lymphoma, nasal type.

Study Overview

• Status: Completed
• Conditions: Extranodal NK-T-Cell Lymphoma, Nasal Type
• Intervention / Treatment: Drug: MEDA; Procedure: Auto-HSCT

Detailed Description

Extranodal natural killer/T-cell lymphoma (ENKTCL), nasal type, is a rare subtype of non-Hodgkin lymphoma (NHL) with relatively high incidence in China. L-asparaginase based chemotherapy improved overall response and prolonged the long-term survival for patients with stage IV. But the optimal treatment schedule has not been established. This study is designed with four cycles MEDA chemotherapy, followed by Auto-HSCT for stage IV patients with newly onset, relapsed or refractory diseases. The efficacy and safety of this protocol in the treatment of will be measured.

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Zhongshan Hospital, Fudan University
    • Shanghai, Shanghai, China, 200011
      • Shanghai Ninth People's Hospital
    • Shanghai, Shanghai, China, 200092
      • Xinhua Hospital
    • Shanghai, Shanghai, China, 200120
      • Shanghai Dong Fang Hospital
    • Shanghai, Shanghai, China, 200031
      • Shanghai Eye Ear Nose and Throat Hospital, Fudan University
    • Shanghai, Shanghai, China, 200336
      • Shanghai Tong Ren Hospital
  • Xinjiang
    • Urumqi, Xinjiang, China, 830001
      • Xin Jiang People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Pathological diagnosis of extranodal natural killer/T-cell lymphoma, nasal type based on WHO 2008 classification of tumors of haematopoietic and lymphoid tissue.

Eastern Cooperative Oncology Group (ECOG ) performance status 0~3.

Stage IV disease with at least one measurable lesion.

Preserved organ functions for: Platelet>50×10*9/L, hemoglobin>80g/L, total bilirubin (TBIL)<3×ULN, alanine transaminase (ALT)<5×ULN, serum creatinine (Cr)<1.5×ULN, fibrinogen≥0.5g/L, LVEF≥50%.

Signed Informed consented.

Exclusion Criteria:

Relapsed or progressive disease to prior L-asparaginase-based chemotherapy.

Concurrent cancers need surgery or chemotherapy within 6 months.

History of chemotherapy or radiotherapy for other solid cancers within 3 years.

Recent history of radiotherapy of upper-aero-digestive tract within last 3 months.

Significant complications: LVEF≤50%, coagulopathy, autoimmune disease, severe infection, or liver cirrhosis, severe hemophagocytic lymphohistiocytosis.

Mental disorders.

Pregnant or lactation.

HIV, hepatitis virus C (HCV), or active hepatitis virus B (HBV) infection with HBV DNA≥10*5 copies/ml.

History of pancreatitis.

Known history for grade 3/4 allergy to the drugs in chemotherapy regimen.

Enrolled in other trial treatment.

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: MEDA/Auto-HSCT; Patients will be initially treated with four cycles MEDA chemotherapy, followed by autologous hematopoietic stem cell transplantation (Auto-HSCT).

Drug: MEDA; Methotrexate, 3.0g/m2/d iv, day 1 Etoposide, 100mg/m2 iv, day 2 to day 4 Dexamethasone, 40mg/d iv, day 1 to day 4 Pegaspargase, 2500IU/m2/d im, day 4 The MEDA chemotherapy will be repeated every 3 weeks.; Other Names: Methotrexate, Etoposide,Dexamethasone,Pegaspargase; Procedure: Auto-HSCT; Auto-HSCT will be performed with patients who responded to the initial MEDA chemotherapy with standard BEAM conditioning regimen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response rate	The complete response rate will be assessed on day 28 of the 4th course of MEDA chemotherapy.	Day 28 of the 4th course of MEDA chemotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Progression free survival is the time from entry onto the treatment until lymphoma progression or death of any reason.	2-year
Overall survival	Overall survival is defiend as the time from entry onto the treatment until death of any reason	2-year
Overall response rate	The overall response rate will be assessed on day 28 of the 4th course of MEDA chemotherapy.	Day 28 of the 4th course of MEDA chemotherapy
Treatment-Related Adverse Events as Assessed by CTCAE v4.0	Treatment-Related Adverse Events will be assessed and graded by NCI CTCAE v4.0.	Day 1 of each course of chemotherapy and then every 3 months for 2 years

Collaborators and Investigators

• Sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
• Investigators: Study Chair: Rong Tao, MD, Xinhua hospital, Shanghai Jiao Tong University of Medicine

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Actual): February 1, 2020
• Study Completion (Actual): February 1, 2020

Study Registration Dates

• First Submitted: April 29, 2016
• First Submitted That Met QC Criteria: May 3, 2016
• First Posted (Estimate): May 6, 2016

Study Record Updates

• Last Update Posted (Actual): April 27, 2020
• Last Update Submitted That Met QC Criteria: April 24, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• 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; Autonomic Agents; Peripheral Nervous System 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; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Dexamethasone; Etoposide; Methotrexate; Pegaspargase
• Other Study ID Numbers: XHLSG-NK-1602

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO