Compare Efficacy of CHOP Versus Fractionated ICED in Transplant-eligible Patients With Previously Untreated PTCL

Study Overview
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Brief Summary
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This study is a Randomized Phase II Study to Compare Efficacy of CHOP versus Fractionated ICED in Transplant-eligible Patients with Previously Untreated Peripheral T-cell Lymphoma.

Detailed Description
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It recommends that the CHOP regimen in the primary T-cell lymphoma therapies currently used but did not get satisfactory effect of therapy (progression-free survival 40%), primarily to consider the clinical trial at NCCN guideline.But why the CHOP regimen is widely used because physicians are accustomed to use. Fractionated ICED therapy is a therapy by adjusting the Original ICE regimen.This is how the capacity of Ifosfamide divided into three days. (Fractionated ifosfamide).Original ICE therapy has been widely used as a salvage therapy of patients with relapsed or refractory lymphoma for a long time, it has been recommended as part of primary therapy of T-cell lymphoma.But Fractionated ICED is added to dexamethasone therapy in order to improve the effectiveness as a primary therapy.The recurrent lymphoma in 75 patients with treatment after Fractionated ICE when the self-stem cell transplantation, showed a more than 40% progression-free survival.Thus treatment of Fractionated ICED targeting previously untreated patients, and if a combination of high-dose dexamethasone to expect to be able to induce a progression-free survival of 60% or more.

Official Title
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Randomized Phase II Study to Compare Efficacy of CHOP Versus Fractionated ICED in Transplant-eligible Patients With Previously Untreated Peripheral T-cell Lymphoma

Conditions
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Peripheral T-cell Lymphoma

Intervention / Treatment
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* Drug: CHOP
* Drug: fractionated ICED


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 19-65 years Informed consent Subject able to adhere to the study visit schedule and other protocol requirements. Histologically proven Peripheral T-cell Lymphoma,No prior chemotherapy for the treatment of Peripheral T-cell Lymphoma It includes the following subtypes. PTCL, not otherwise specified Angioimmunoblastic T-cell lymphoma Anaplastic large cell lymphoma, ALK-negative type Enteropathy-associated T-cell lymphoma Hepato-splenic T-cell lymphoma Subcutaneous panniculitis-like T-cell lymphoma Primary cutaneous gamma-delta T-cell lymphoma Primary cutaneous CD8+ aggressive epidermotropic lymphoma Other non classifiable T-cell Lymphoma Performance status (ECOG) 0,1 or 2 A negative pregnancy test prior to treatment must be available both for pre-menopausal women Female of childbearing potential (FCBP) must: contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) while on IP; and for 3 months following the last dose of IP.Male subjects must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions, and for 3 months following IP discontinuation. life expectancy≥90day(3months) Exclusion Criteria: Other serious medical illnesses or psychiatric disorders Any state that the confusion in the interpretation of test result. Other type lymphoma ex) B-cell lymphoma Other type T-cell lymphoma Adult T-Cell Leukemia/Lymphoma NK/T-cell Lymphoma, Nasal Type ALK-Positive Anaplastic Large-Cell Lymphoma Cutaneous Tcell lymphoma primary cutaneous CD30+ lympho- proliferative disorder primary cutaneous Anaplastic T cell lymphoma Previously treated for PTCL(Except for a short period before randomization of corticosteroids (a period of not more than 8 days) Previous radiation therapy CNS involvement. If the contraindication to chemoherapy Subject has known historical or active infection with HIV. BM function: ANC < 1.5 × 109/L; Platelet count <100,000/mm2 (100 × 109/L), SGOT/AST or SGPT/ALT ≥ 3.0 x ULN, Bilirubin> 2 x upper normal value serum creatinine level > 2.0 x ULN Any other malignancies within the past 3 years except curatively treated non-melanoma skin cancer or in situ carcinoma of cervix uteri MUGA scan <45% Those who administered doxorubicin exceeding 200 mg / m2 Subject has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy. Breast-feeding or pregnant female

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CHOP<br>cyclophosphamide, 750mg/m² IV day1 doxorubicin, 50 mg/m² IV day1 vincristine, 1.4 mg/m² (max 2 mg) IV day1 prednisone ,40 mg/m² PO day1 5 every 3 weeks | Drug: CHOP<br>* cyclophosphamide, 750mg/m² IV day1 doxorubicin, 50 mg/m² IV day1 vincristine, 1.4 mg/m² (max 2 mg) IV day1 prednisone ,40 mg/m² PO day1 5 every 3 weeks<br>* Other names: cyclophosphamide, cyclophosphamide, vincristine,prednisone;Drug: fractionated ICED<br>* ifosfamide, 1.67 g/m² IV day1 3 carboplatin, AUC =5 IV day1 etoposide, 100mg/m² IV day1 3 dexamethasone 40 mg PO or IV day1 4 every 3 weeks<br>* Other names: ifosfamide, carboplatin, etoposide, dexamethasone;|
| Experimental: Fractionated ICED<br>ifosfamide, 1.67 g/m² IV day1 3 carboplatin, AUC =5 IV day1 etoposide, 100mg/m² IV day1 3 dexamethasone 40 mg PO or IV day1 4 every 3 weeks | Drug: CHOP<br>* cyclophosphamide, 750mg/m² IV day1 doxorubicin, 50 mg/m² IV day1 vincristine, 1.4 mg/m² (max 2 mg) IV day1 prednisone ,40 mg/m² PO day1 5 every 3 weeks<br>* Other names: cyclophosphamide, cyclophosphamide, vincristine,prednisone;Drug: fractionated ICED<br>* ifosfamide, 1.67 g/m² IV day1 3 carboplatin, AUC =5 IV day1 etoposide, 100mg/m² IV day1 3 dexamethasone 40 mg PO or IV day1 4 every 3 weeks<br>* Other names: ifosfamide, carboplatin, etoposide, dexamethasone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression free survival | Time to disease progression is defined as the time from treatment start to the first recording of relapse or disease progression or death of any cause | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Duration of survival is defined as the time from treatment start to death of any cause or the date of last follow-up. Subjects who are alive will be censored using the date at which they are last known to be alive | 3 years | 
| overall response rate | They should be classified as complete remission(CR),Partial remission(PR),Stable disease(SD), or progression disease(PD)according to the Revised Response Criteria for Malignant Lymphoma | 3 years | 
| Response duration |  | 3 years | 
| Toxicity profiles | Toxicity profiles as measured by Adverse Events and Laboratory results. | 3 years |