Chidamide Plus CHOEP Combined With Upfront ASCT in Untreated Peripheral T-cell Lymphoma

Study Overview
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Brief Summary
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The purpose of this study is to determine determine the maximum tolerated dose (MTD) and safety of the combination of Chidamide combined with CHOEP(cyclophosphamide， epirubicin,vindesine, etoposide and prednisone) regimen as first line treatment in newly-diagnosed T-NHL.

Detailed Description
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Chidamide+Cyclophosphamide+Epirubicin+Vindesine+Etoposide+Prednisone Six cycles of therapy administered every 28 days were planned. Cyclophosphamide 750mg/m2 IV d1; epirubicin 70mg/m2 IV d1; Vindesine 4mg IV d1; etoposide 100mg IV d1-3; prednisone 60mg/m2 PO d1-5. Chidamide: Phase I: Patients were treated at the following bortezomib dose levels: 15, 20, and 25 mg twice per week. Dose escalation and reduction were on the basis of the continual reassessment method, with at least two patients per dose level and no dose level skipped. No intrapatient dose escalation will be allowed. If one patient experienced dose-limiting toxicity (DLT), three additional patients were added to the dose level. If two of six patients experienced DLT, the previous dose level was declared the MTD. If only one of six patients experienced DLT, dose escalation was permitted to continue. DLT refers only to toxic events that occur during the first cycle of treatment. At least 9(3+3+3) patients will be enrolled in Phase I study. Phase II: If MTD was not reached at 25mg dose level of Chidamide. The followed study will use 20mg twice per week as experimental dose. After 3 Cycles, patients who become PD should withdraw the trial and receive other regimens; patients who become CR and eligible for auto-SCT will undergo auto-SCT; patients who get PR will receive 3 more cycles C-CHOEP regimen treatment, CR patients in them undergo auto-SCT, non-CR patients undergo follow-up phase. All the patients will continue to receive chidamide treatment until progression of the disease (PD), unacceptable toxicity, or patient/investigator discretion. During follow-uo phase, surveillance imaging with CT scans can be performed every 6 months up to the first 2 years, followed by doctor visit every 6 months up to 5 years or the disease relapses. from recruiting the first subject until the last recruited subject finished his 2 years follow-up phase or the disease relapsed

Official Title
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Chidamide Plus CHOEP Combined With Upfront ASCT in Untreated Peripheral T-cell Lymphoma

Conditions
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T Cell Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: Chidamide
* Drug: Cyclophosphamide
* Drug: Epirubicin
* Drug: Vindesine
* Drug: Etoposide
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly-diagnosed T cell non-Hodgkin's lymphoma patients. Diagnosis of T cell NHL was performed by morphologic analysis of tissue pathological specimens along with Immunohistochemistry (IHC) ECOG≤2 At least one or more unidimensionally measurable lesions (≥1 cm by CT scan or skin lesions or a measurable lesion by physical examination) Sign the Informed consent Women of childbearing potential must understand that the study medication could have a potential teratogenic risk. They should undergo complete contraception during the study period. Male subjects must agree to use condoms throughout study drug therapy. Exclusion Criteria: T lymphoblastic leukemia/lymphoma Bone marrow involvement and lymphoma cell ≥ 25% Aplastic large T cell lymphoma - ALK positive NK/T-cell lymphoma Mycosis Fungoides/Sezary Syndrome Pre-existing uncontrolled active infection Clinical evidence of grade 3 or 4 heart failure as defined by the New York Heart Association criteria Grade 3 or 4 peripheral neuropathy Pregnancy or active lactation Co-existing tumors Impaired renal/ hepatic function (serum creatinine >1.5 mg/dl or creatinine clearance <60 ml/min or serum transaminases/ bilirubin ≥3 upper limits of normal） History of mental illness

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: C-CHOEP<br>experimental arm will be treated by Chidamide combined CHOEP ( cyclophosphamide, epirubicine, vindesine, etoposide and prednisone) regimen for 6 cycles. | Drug: Chidamide<br>* Six cycles of therapy will be administered,and each cycle of treatment is 28 days. Phase I: Patients were treated at the following dose levels: 15, 20, and 25 mg twice per week to determine the MDT Phase II: If MTD was not reached at 25mg dose level of Chidamide. The followed study will use 20mg twice per week as experimental dose.<br>* Other names: epidaza;Drug: Cyclophosphamide<br>* Cyclophosphamide(750mg/m2) was administered intravenously on d1<br>Drug: Epirubicin<br>* epirubicin (70mg/m2)was administered intravenously on d1;<br>Drug: Vindesine<br>* vindesine (4mg)was administered intravenously on d1;<br>Drug: Etoposide<br>* etoposide (100mg) was administered intravenously on d1,2,3.<br>Drug: Prednisone<br>* prednisone (60mg/m2)was administered intravenously by oral d1-5.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2 years progression-free survival | from recruiting the first subject until the last recruited subject finished his 2 years follow-up phase or the disease relapsed | the overall time frame is up to 48 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 5 years overall survival（OS） | from recruiting the first subject until the last recruited subject finished his 5 years follow-up phase | the overall time frame is up to 84 months | 
| overall response rate(ORR) and complete remission rate(CR） | the last recruited subject finished 4 cycle C-CHOEP regimen | the overall time frame is up to 30 months | 
| adverse events | throughout the treatment and until 30 days after the administration of the last dose of a study drug | the overall time frame is up to 84 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chidamide, T Cell Non-Hodgkin's Lymphoma