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

NCT ID: NCT02825147

Last Updated: 2017-11-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-30
• Study Completion Date: 2017-07-31

Brief Summary

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.

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.

Conditions

Nasal Type Extranodal NK/T-Cell Lymphoma

Keywords

pegaspargase,methotrexate

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Pegaspargase

Intervention Type: DRUG

Methotrexate

Intervention Type: DRUG

Dexamethasone

Intervention Type: DRUG

Etoposide

Intervention Type: DRUG

radiotherapy

Intervention Type: RADIATION

Interventions

Pegaspargase

Intervention Type: DRUG

Methotrexate

Intervention Type: DRUG

Dexamethasone

Intervention Type: DRUG

Etoposide

Intervention Type: DRUG

radiotherapy

Intervention Type: RADIATION

Eligibility Criteria

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

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ruijin Hospital

OTHER

Sponsor Role: lead

Responsible Party

Zhao Weili

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

ZHAO WEILI, PhD,MD

Role: PRINCIPAL_INVESTIGATOR

Ruijin Hospital

Locations

Shanghai Ruijin Hospital

Shanghai, , China

Countries

China

Other Identifiers

Shanghai Ruijin Hospital

Identifier Type: -

Identifier Source: org_study_id