CEOP/IVE/GDP Compared With CEOP as the First-line Therapy for Newly Diagnosed Adult Patients With PTCL

Study Overview
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Brief Summary
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Peripheral T-cell Lymphoma (PTCL) is a heterogenic malignancy with poor outcome. Five-year PFS and OS for these patients received classic CHOP regimen (cyclophosphamide, vincristin, doxorubicin and prednisone) is less than 30%.High dose intensive chemotherapy doesn't demonstrate better response. At present, there is no standardized treatment protocol for this kind of lymphoma. So, clinical trials are encouraged by NCCN for those patients.

Detailed Description
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For the less efficacy of CHOP or CHOP-like regimen, multi-drug combination strategy has been the therapy tendency in PTCL. The novel regimen IVE/MTX (ifosfamide, etoposide，epirubucin/methotrexate)-ASCT(autologous stem-cell transplantation ) was piloted for patients eligible for intensive treatment, followed by auto-stem cell transplantation. Five-years PFS (progression-free survival) and OS (overall survival) were 52% and 60% respectively, significantly improved compared with the historical group treated with anthracycline-based chemotherapy. The encouraged results were extended to the peripheral T cell lymphoma-non specified (PTCL-NOS). Former studies reported that GDP (gemcitabine, cis-platinum, and dexamethasone) compared with CHOP as the therapy strategy for PTCL-NOS (not otherwise specified). The response rate was 78.57% in GDP group and 60.00% in CHOP group respectively. DFS (disease-free survival) was 9.79 and 4.2 months in above two groups. They concluded that GDP is superior with CHOP. The main side-effect of two regimens is hematological toxicity. Furthermore, high-dose combined with ASCT has been the first-line therapy for PTCL. However, only about 30% patients with PTCL have chance to receive ASCT for multiple reasons. So it is urgent to explore new combination-therapy regimen to improve the outcome for patients with PTCL. The aim of our study is to compare the response and survival rate of CEOP/IVE/GDP (cyclophosphamide, vincristin, epirubucin and prednisone/ ifosfamide, epirubucin, and etoposide/ gemcitabine, cis-platinum, and dexamethasone) with those of CEOP regimen, looking forward to its superiority in efficacy and safety for the newly diagnosed adult patients with PTCL.

Official Title
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CEOP/IVE/GDP Compared With CEOP as the First-line Therapy for Newly Diagnosed Adult Patients With Peripheral T-cell Lymphoma (PTCL)

Conditions
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Peripheral T-Cell Lymphoma, Not Otherwise Specified, Angioimmunoblastic T Cell Lymphoma, ALK-negative Anaplastic Large Cell Lymphoma, Enteropathy Associated T Cell Lymphoma, Subcutaneous Panniculitis Like T Cell Lymphoma, Hepatosplenic T-cell Lymphoma

Intervention / Treatment
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* Drug: CEOP/IVE/GDP chemotherapy regimen
* Drug: CEOP chemotherapy regimen for 6 cycles


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed, histologically confirmed the following pathology subtype according to WHO 2008 classification: peripheral T Cell Lymphoma, not otherwise specified, angioimmunoblastic T cell lymphoma, ALK-negative anaplastic large cell lymphoma, enteropathy associated T cell lymphoma, subcutaneous panniculitis like T cell lymphoma, and hepatosplenic T-cell lymphoma. ≥ 16 years of age. Performance status of 2 or less. Has no history of malignancy. Has radiologically measurable disease. Life expectancy ≥6 months. Voluntarily sign an informed consent. Exclusion Criteria: Pathology subtype with NK/T cell lymphoma, ALK positive-ALCL. Primary central nervous system (CNS) lymphoma. Previous systemic chemotherapy or local therapy. Has undergone hematopoietic stem-cell transplantation (HSCT). Has active infectious disease requiring general antibiotics, anti-fungal or anti-virus therapy. Has uncontrollable cardiocerebrovascular, coagulative, autoimmune, or serious infectious disease. Echocardiography shows left ventricular ejection fraction (LVEF) ≤ 50%. Inadequate renal, hepatic or bone marrow function Active liver or biliary disease. Has other uncontrollable medical condition that may interfere with their participation in the study. Woman in pregnancy or lactation. Patient is known to be positive for Human immunodeficiency virus (HIV) infection.

Ages Eligible for Study
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Minimum Age: 16 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 |
| --- | --- |
| Experimental: CEOP/IVE/GDP chemotherapy regimen<br>2 cycles of CEOP(cyclophosphamide,vincristine, epirubucin and prednisone),2 cycles of IVE(ifosfamide, epirubucin, etoposide)and 2 cycles of GDP(gemcitabine, cis-platinum, and dexamethasone) | Drug: CEOP/IVE/GDP chemotherapy regimen<br>* CEOP: Cyclophosphamide 750mg/m2, ivgtt D1 Epirubucin 70mg/m2,ivgtt D1 Vincristine 1.4mg/m2（max 2mg）, ivgtt D1 Prednisone 60mg/m2 （max 100mg）,PO,D1-D5 IVE: Ifosfamide 2000mg/m2,ivgtt D1-D3 Epirubucin 70mg/m2, ivgtt D1 Etoposide 100mg/m2, ivgtt D1-D3 GDP: Gemcitabine 1g/m2,ivgtt D1,D8 Cis-platinum 25mg/m2, ivgtt D1-D3 Dexamethasone 40mg, ivgtt D1-D4<br>|
| Active Comparator: CEOP chemotherapy regimen for 6 cycles<br>6 cycles of CEOP regimen(cyclophosphamide,vincristin,epirubucin and prednisone) | Drug: CEOP chemotherapy regimen for 6 cycles<br>* CEOP: Cyclophosphamide 750mg/m2, ivgtt D1 Epirubucin 70mg/m2,ivgtt D1 Vincristine 1.4mg/m2（max 2mg）, ivgtt D1 Prednisone 60mg/m2 （max 100mg）,PO,D1-D5 every 21 days for total 6 courses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with complete remission （CR） |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival |  | 2 year since randomization | 
| overall survival |  | 2 year since randomization | 
| overall response rate |  | 6 months | 
| adverse events |  | from randomization to one month after last cycle of treatment |