Pegaspargase and Methotrexate Based Regimens for Newly Diagnosed Extranodal NK/T Cell Lymphoma

November 10, 2017 updated by: Zhao Weili, Ruijin Hospital
Extranodal NK/T cell lymphoma is an aggressive tumor with higher incidence in Asia.Traditional CHOP/CHOP-like regiment can't produce satisfied outcome for the patients. Asparaginase-based treatment has been demonstrated as promising response rate and survival superiority. Stage-specified regimen may bring out exciting efficacy with good safety.

Study Overview

Detailed Description

Extranodal NK/T cell lymphoma is a kind of tumor more prevalent in Asia and South America than that in the Western world, which is almost invariably EBV- associated and often presents as localized disease in and around the nasal structures. The disease frequency was higher in Asian countries with no differences in age, gender or immunophenotypic profile between nasal and extranasal cases. EBV is a constant finding, particularly in the cases presenting as localized nasal disease and assumed involved in the pathogenesis. During the past decades the disease, historically termed as "lethal midline granuloma" was very aggressive with poor survival. Five-year OS for extra-nasal disease is reported as 9% compared to 42% for localized disease.

Although radiotherapy combined with or without anthracycline-based chemotherapy has been considered as the treatment for extranodal NK/T cell lymphoma in the past, numerous data suggest that this tumor is not very chemosensitive due to the p-glycoprotein expression, which may mediate the drug resistance. CHOP/CHOP-like schedules presented with low CR rates and frequent failures during chemotherapy. Disseminated involvement is much poorer in prognosis than localized disease with the latter is benefit more from radiotherapy.

In the nearest ten years, many new agents have been used in the treatment of extranodal NK/T cell lymphoma, in which the most promising one is asparaginase. Asparaginase-containing regiment has demonstrated about 50% responses rates and 5-year overall survival of 65% in relapsed or refractory disease. The impressive outcome indicates its value in the newly diagnosed patients, especially in the disseminated cases. Pegaspargase as a new form of asparaginase displays equivalent bioactivity as L- asparaginase with longer half-time and lower incidence of allergy. Its clinical efficacy has been verified in the patients with acute lymphocytic leukemia.

The purpose of this study is to evaluate the efficacy and safety of pegaspargase and methotrexate based regimens with or without radiotherapy in the newly diagnosed patients with extranodal NK/T cell lymphoma, including localized and disseminated cases.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Shanghai, China, 200025
        • Shanghai Ruijin Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years to 68 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Pathological diagnosis of extranodal NK/T cell lymphoma, nasal type, previously untreated
  • Age 14 ~ 70 years old
  • ECOG(Eastern Cooperative Oncology Group)performance status 0~2
  • Stage I to II
  • Life expectancy>6 months
  • Informed consented

Exclusion Criteria:

  • Chemotherapy before
  • Bone marrow transplantation before
  • History of malignancy
  • Uncontrollable cardio-cerebral vascular, coagulative, autoimmune, serious infectious disease
  • LVEF≤50%
  • Other uncontrollable medical condition that may that may interfere the participation of the study
  • Lab at enrollment ALT or AST >3*ULN, AKP or bilirubin >2.5*ULN Creatinine>1.5*ULN
  • Not able to comply to the protocol for mental or other unknown reasons
  • Pregnant or lactation
  • HIV infection

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: MESA
stage I/II: methotrexate 1000mg/m2,d1 dexamethasone 40mg,d2-d4 etoposide 100mg,d2-d4 pegaspargase 2500U/m2,d5 a cycle of every 21 days with totally 4 cycles Radiotherapy at least 50Gy in dose for the involved local focus is sandwiched after 2 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Overall response rate
Time Frame: 21 days after 4 cycles of chemotherapy
21 days after 4 cycles of chemotherapy

Secondary Outcome Measures

Outcome Measure
Time Frame
Progression free survival
Time Frame: 2-year
2-year
overall survival
Time Frame: 2-year
2-year
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0
Time Frame: Day 1 of each course and then every 3 months for 1 years
Day 1 of each course and then every 3 months for 1 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: ZHAO WEILI, PhD,MD, Ruijin Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2013

Primary Completion (Actual)

March 1, 2016

Study Completion (Actual)

July 1, 2017

Study Registration Dates

First Submitted

November 22, 2015

First Submitted That Met QC Criteria

July 3, 2016

First Posted (Estimate)

July 7, 2016

Study Record Updates

Last Update Posted (Actual)

November 14, 2017

Last Update Submitted That Met QC Criteria

November 10, 2017

Last Verified

November 1, 2017

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Nasal Type Extranodal NK/T-Cell Lymphoma

Clinical Trials on Methotrexate

3
Subscribe