VP-16, Ifosfamide, Dexamethasone, L-asparaginase Chemotherapy in Patients With Extranodal Natural Killer T Cell Lymphoma (VIDL+ASCT)

Sponsor

Samsung Medical Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT02544425

Collaborator

(none)

Enrollment

Locations

Arm

69.3

Anticipated Duration (Months)

13.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Open-labeled, multicenter phase II study of VIDL (VP-16, Ifosfamide, Dexamethasone, L-asparaginase) chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation in patients with stage III/IV extranodal NK/T-cell Lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Extranodal NK-T-Cell Lymphoma	Drug: Etoposide Drug: Ifosfamide Drug: Dexamethasone Drug: L-asparaginase Drug: Busulfan Drug: Melphalan	Phase 2

Detailed Description

Extranodal NK/T cell lymphoma (ENKTL) is a rare and aggressive lymphoma subtype, but standard front-line therapy has not been established. The clinical outcome of patients (pts) with ENKTL after the treatment of conventional chemotherapy, especially pts with advanced stage, was generally poor. Therefore, high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) as a consolidation could be one of promising strategies to improve the outcome of ENKTL. However, there have been few studies reporting the survival outcome or prognostic significances of front-line ASCT in pts with ENKTL. Thus, the aim of this study was to investigate the outcome of patients with advanced-stage ENKTL who had undergone front-line ASCT.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

27 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase II Study of VIDL (VP-16, Ifosfamide, Dexamethasone, L-asparaginase) Chemotherapy Followed by High-dose Chemotherapy and Autologous Stem Cell Transplantation in Patients With Stage III/IV Extranodal NK-T-Cell Lymphoma

Actual Study Start Date :

Feb 21, 2016

Anticipated Primary Completion Date :

Aug 31, 2021

Anticipated Study Completion Date :

Nov 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: VIDL+ASCT VIDL Induction (repeated 28 days) : VP-16, Ifosfamide, Dexamethasone, L-asparaginase Peripheral blood stem cell mobilization:Etoposide Conditioning regimen for autologous stem cell transplantation:Busulfan,Melphalan,Etoposide	Drug: Etoposide Subjects will receive Etoposide 100 mg/m2 + 5% dextrose in water 500 mL intravenous over 90 mins D1-3 of VIDL chemotherapy. After that, Etoposide will be administered 375mg/m2 D1-2 with G-colony stimulating factor (10 ug/kg) injection in step of Peripheral Blood Stem Cell Collection. Also It will be administered 400mg/m2 on conditioning regimen. Other Names: VP-16 Drug: Ifosfamide It will be administered1.2g/m2 + 5% dextrose in water 100 mL intravenous over 1 hr D1-3 Drug: Dexamethasone It will be administered 40mg/day PO or IV D1-3 Drug: L-asparaginase It will be administered 4000 IU/m2 intramuscular D8, 10, 12, 14, 16, 18, 20 Drug: Busulfan Conditioning regimen for autologous stem cell transplantation: Busulfan 3.2 mg/kg D -8, -7, -6 Drug: Melphalan Conditioning regimen for autologous stem cell transplantation: Melphalan 70 mg/m2 D -3, -2

Arm

Intervention/Treatment

Experimental: VIDL+ASCT

VIDL Induction (repeated 28 days) : VP-16, Ifosfamide, Dexamethasone, L-asparaginase Peripheral blood stem cell mobilization:Etoposide Conditioning regimen for autologous stem cell transplantation:Busulfan,Melphalan,Etoposide

Drug: Etoposide

Subjects will receive Etoposide 100 mg/m2 + 5% dextrose in water 500 mL intravenous over 90 mins D1-3 of VIDL chemotherapy. After that, Etoposide will be administered 375mg/m2 D1-2 with G-colony stimulating factor (10 ug/kg) injection in step of Peripheral Blood Stem Cell Collection. Also It will be administered 400mg/m2 on conditioning regimen.

Other Names:

VP-16

Drug: Ifosfamide

It will be administered1.2g/m2 + 5% dextrose in water 100 mL intravenous over 1 hr D1-3

Drug: Dexamethasone

It will be administered 40mg/day PO or IV D1-3

Drug: L-asparaginase

It will be administered 4000 IU/m2 intramuscular D8, 10, 12, 14, 16, 18, 20

Drug: Busulfan

Conditioning regimen for autologous stem cell transplantation: Busulfan 3.2 mg/kg D -8, -7, -6

Drug: Melphalan

Conditioning regimen for autologous stem cell transplantation: Melphalan 70 mg/m2 D -3, -2

Outcome Measures

Primary Outcome Measures

progression-free survival (PFS) [2 years]

Secondary Outcome Measures

objective overall response rate [2 years]
Number of subjects with Adverse Events as a Measure of safety and tolerability [2 years]
overall survival [4 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed extranodal NK/T cell lymphoma
Aged between 19 and 65 years
Previously untreated history
Performance status: Eastern Cooperative Oncology Group 0-2
Ann Arbor stage III and IV
At least one in positron emission tomograph(PET)/CT positive lesion or in 2-dimensional computerized tomography
mass lesions more than 2 cm by conventional CT or more than 1 cm by spiral CT
Skin lesions or physically detected mass more than 2 cm
Cardiac ejection fraction ≥ 45 % as measured by multiple gated acquisition scan(MUGA) or 2D echogram(ECHO) without clinically significant abnormalities
Adequate liver functions: Transaminase (AST/ALT) < 3 X upper normal value(or < 5 x upper limit of normal in the presence of NK/T lymphoma involvement of the liver)
Bilirubin < 2 X upper normal value(or < 5 x upper limit of normal in the presence of DLBCL involvement of the liver)
Serum Creatinine < 2.0 mg/dL
Adequate bone marrow functions: hemoglobin ≥ 9 g/dL absolute neutrophil count (ANC) ≥ 1,500/μL and platelet count ≥ 75,000/μL, unless abnormalities are due to bone marrow involvement by lymphoma
Expected life is more than 180 days (more than 6 months)
A negative serum or urine pregnancy test prior to treatment must be available both for pre-menopausal women and for women who are < 1years after the onset of menopause. Premenopausal women should be treated with appropriate contraception such as hormone contraception, intra-uterine device, spermicidal condom and etc. during and one month after the treatment.
Voluntarily signed the informed consent including fully understand of clinical procedures and processing steps for the clinical trial

Exclusion Criteria:

Patients who have serious medical condition, abnormal laboratory results or psychiatric problems
Other subtypes non-Hodgkin's lymphoma than NK/T cell lymphoma
Patients who have aggressive NK/T cell leukemia
NK/T cell lymphoma with Primary Central Nervous System (CNS) involvement. However, patients who have only had prophylactic intrathecal chemotherapy against CNS disease are eligible.
Patients with a known history of HIV seropositivity or hepatitis C virus (HCV) (+). Patients who have carrier hepatitis B virus (HBV) (+) are eligible. However, primary prophylaxis using antiviral agents is recommended for HBV carrier to prevent HBV reactivation during whole treatment period.
Any other malignancies within the past 5 years except curatively treated non-melanoma skin cancer or in situ carcinoma of cervix uteri
Pregnant or lactating women, women of childbearing potential not employing adequate contraception
Other serious illness or medical conditions i. Unstable cardiac disease despite treatment, myocardial infarction within 6 months prior to study entry ii. History of significant neurologic or psychiatric disorders including dementia or seizures iii. Active uncontrolled infection (viral, bacterial or fungal infection) iv. Other serious medical illnesses
Concomitant administration of any other experimental drug under investigation, or concomitant chemotherapy, hormonal therapy, or immunotherapy.
Serious allergy history for experimental drugs
Patients who contraindication to the study drug use