Clinical trial NCT02825147: Pegaspargase and Methotrexate Based Regimens for Newly Diagnosed Extranodal NK/T Cell Lymphoma
Official title: Pegaspargase and Methotrexate Based Regimens for Newly Diagnosed Extranodal NK/T Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nasal Type Extranodal NK/T-Cell Lymphoma
Keywords: pegaspargase,methotrexate
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
First posted: 2016-07-07
Enrollment: 40
Sex: ALL
Minimum age (years): 14
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Overall response rate
timeFrame: 21 days after 4 cycles of chemotherapy
Secondary outcomes:
measure: Progression free survival
timeFrame: 2-year
measure: overall survival
timeFrame: 2-year
measure: Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0
timeFrame: Day 1 of each course and then every 3 months for 1 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Ruijin Hospital
Study officials:
affiliation: Ruijin Hospital
name: ZHAO WEILI, PhD,MD
role: PRINCIPAL_INVESTIGATOR
References: