T Cell Non-Hodgkin's Lymphoma
Conditions
Keywords
Chidamide, T Cell Non-Hodgkin's Lymphoma
Brief summary
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
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
Interventions
DRUGChidamide
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.
DRUGCyclophosphamide
Cyclophosphamide(750mg/m2) was administered intravenously on d1
DRUGEpirubicin
epirubicin (70mg/m2)was administered intravenously on d1;
DRUGVindesine
vindesine (4mg)was administered intravenously on d1;
DRUGEtoposide
etoposide (100mg) was administered intravenously on d1,2,3.
DRUGPrednisone
prednisone (60mg/m2)was administered intravenously by oral d1-5.
Sponsors
Chinese PLA General Hospital
Peking University First Hospital
Peking University Third Hospital
Peking University Cancer Hospital & Institute
Tianjin Medical University Cancer Institute and Hospital
Peking Union Medical College Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 2 years progression-free survival | the overall time frame is up to 48 months | from recruiting the first subject until the last recruited subject finished his 2 years follow-up phase or the disease relapsed |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 5 years overall survival（OS） | the overall time frame is up to 84 months | from recruiting the first subject until the last recruited subject finished his 5 years follow-up phase |
| overall response rate(ORR) and complete remission rate(CR） | the overall time frame is up to 30 months | the last recruited subject finished 4 cycle C-CHOEP regimen |
| adverse events | the overall time frame is up to 84 months | throughout the treatment and until 30 days after the administration of the last dose of a study drug |
Other
| Measure | Time frame | Description |
|---|---|---|
| maximum tolerated dose of chidamide | the overall time frame is up to 6 months | from recruiting the first 9 subjects to all of them received 1 cycle C-CHOEP regiment |
Countries
China
Contacts
Primary ContactWei Zhang, M.D
Backup ContactYan Zhang, M.D
Outcome results
None listed