UMIN-CTR Clinical Trial

Public title

Phase II study of SMILE chemotherapy
for stage IV or relapsed/refractory extranodal NK/T-cell lymphoma

Acronym

Phase II study of SMILE chemotherapy
for stage IV or relapsed/refractory extranodal NK/T-cell lymphoma

Scientific Title

Phase II study of SMILE chemotherapy
for stage IV or relapsed/refractory extranodal NK/T-cell lymphoma

Scientific Title:Acronym

Phase II study of SMILE chemotherapy
for stage IV or relapsed/refractory extranodal NK/T-cell lymphoma

Region

Japan

Asia(except Japan)

Condition

extranodal NK/T-cell lymphoma, nasal type

Classification by specialty

Hematology and clinical oncology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

To establish a more effective therapy for extranodal NK/T-cell lymphoma, nasal type, with untreated stage IV or relapsed/refractory state, we plan a safety and efficacy study of SMILE (Steroid=dexamethasone, Methotrexate, Ifosfamide, L-asparaginase and Etoposide) regimen.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Developmental phase

Phase II

Primary outcomes

overall response rate

Key secondary outcomes

complete response rate (%CR), 1-year overall survival, response stratified by frontline/relapsed/refractory categorization, response stratified by the prior regimen of chemotherapy (CHOP-like vs. DeVIC-like), and the rate of adverse events

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Two cycles of SMILE chemotherapy consisting from steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide.

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

15

years-old

<=

Age-upper limit

69

years-old

>=

Gender

Male and Female

Key inclusion criteria

1) Histological or cytological diagnosis of extranodal NK/T-cell lymphoma, nasal type, according to the WHO classification. Diagnostic samples should be obtained by surgical or needle biopsy, bone marrow aspiration/biopsy, or peripheral blood cytology.
[Notes: Tumor cells must show immunophenotype of NK/T-cells. They should be CD56-positive and CD20-negative either by immunohistochemistry (IHC) or by flow-cytometry (FCM). For CD56-negative cases, they must be CD3epsilon-positive and CD20-negative by IHC/FCM, and positive for EBV either by Southern blotting or by in-situ hybridization (EBER). At least one cytotoxic molecule (perforin, granzyme B or TIA-1) must be positive.]
2) Disease state must be either of the following:
i) Newly diagnosed Ann Arbor stage IV cases before any chemotherapy
ii) First relapsed/recurrent cases after remission (complete or partial). No chemotherapy or radiotherapy are given within 21 days before registration.
iii) Refractory (either NC or PD) cases with first-line chemotherapy. No chemotherapy or radiotherapy are given within 21 days before registration.
3) Age 15-69 years
4) Performance status (ECOG) 0-2
5) At least one evaluable lesion
6) Patients who received corticosteroids alone are eligible for this study, but those under treatment must be discontinued before registration
7) Patients with sufficient hematopoietic (except for cases with bone marrow involvement or HPS), hepatic, renal, cardiac, and pulmonary function
8) Patient's written informed consent before registration.

Key exclusion criteria

(1) History of hematopoietic stem cell transplant within 12 months
(2) History of allogeneic transplantation
(3) Clinical symptoms of CNS involvement (CSF cytology or brain MRI imaging are not required)
(4) Need for radiation more than 15 Gy including palliation at the time of registration
(5) History of serious adverse reaction(s) by agents including SMILE chemotherapy
(Example: allergy for L-asparaginase, delayed excretion of methotrexate, etc.)
(6) Pleural effusion or ascites except for those with little amount, which cannot be performed pleural or abdominal puncture
(7) Uncontrollable hypertension
(8) History of myocardial infarction or angina or cardiomyopathy
(9) HBs antigen positive
(10) HIV antibody positive
(11) Accompanying interstitial pneumonitis, pulmonary fibrosis, or severe emphysema (all apparently diagnosed by chest X-ray)
(12) Severe infections
(13) Liver cirrhosis, either biopsy proven or clinically diagnosed
(14) Active double cancer: overlapping cancer or asynchronous cancer within 5 years. Carcinoma in situ, intramucosal cancers, and other equivalent lesions are not included for the active double cancer.
(15) Women during pregnancy, lactation period or of childbearing potentials not using a reliable contraceptive method
(16) Use of major tranquilizer, antidepressant, or antimanic
(17) Severe psychosis

Target sample size

28

Name of lead principal investigator

1st name
Middle name
Last name	Kazuo Oshimi

Organization

Juntendo University

Division name

Department of Hematology

Zip code

Address

Hongo, Bunkyo-ku, Tokyo 113-8421, Japan

TEL

Email

Name of contact person

1st name
Middle name
Last name	Motoko Yamaguchi

Organization

Study Coordinator of SMILE-PII

Division name

Department of Hematology and Oncology, Mie University Graduate School of Medicine

Zip code

Address

TEL

Homepage URL

Email

waniwani@clin.medic.mie-u.ac.jp

Institute

NK-cell Tumor Study Group

Institute

Department

Personal name

Organization

Ministry of Health, Labour and Welfare

Organization

Division

Category of Funding Organization

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2007

Year

05

Month

14

Day

URL releasing protocol

Publication of results

Published

URL related to results and publications

http://jco.ascopubs.org/content/early/2011/10/04/JCO.2011.35.6287.long

Number of participants that the trial has enrolled

Results

Patients and Methods: Patients with newly diagnosed stage IV, relapsed, or refractory disease and a performance status of 0 to 2 were eligible. Two cycles of SMILE chemotherapy were administered as the protocol treatment. The primary end point was the overall response rate (ORR) after the protocol treatment. Results: A total of 38 eligible patients were enrolled. The median age was 47 years (range, 16 to 67 years), and the male:female ratio was 21:17. The disease status was newly diagnosed stage IV in 20 patients, first relapse in 14 patients, and primary refractory in four patients. The eligibility was revised to include lymphocyte counts of 500/microL or more because the first two patients died from infections. No treatment-related deaths were observed after the revision. The ORR and complete response rate after two cycles of SMILE chemotherapy were 79% (90% CI, 65% to 89%) and 45%, respectively. In the 28 patients who completed the protocol treatment, 19 underwent hematopoietic stem-cell transplantation. The 1-year overall survival rate was 55% (95% CI, 38% to 69%). Grade 4 neutropenia was observed in 92% of the patients. The most common grade 3 or 4 nonhematologic complication was infection (61%). Conclusion: SMILE chemotherapy is an effective treatment for newly diagnosed stage IV, relapsed or refractory ENKL. Myelosuppression and infection during the treatment should be carefully managed.

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2007

Year

05

Month

12

Day

Date of IRB

Anticipated trial start date

2007

Year

07

Month

01

Day

Last follow-up date

2011

Year

07

Month

01

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2007

Year

05

Month

09

Day

Last modified on

2011

Year

11

Month

09

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000000847