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

Sponsor

Peking Union Medical College Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT02987244

Collaborator

Chinese PLA General Hospital (Other), Peking University First Hospital (Other), Peking University Third Hospital (Other), Peking University Cancer Hospital & Institute (Other), Tianjin Medical University Cancer Institute and Hospital (Other)

100

Enrollment

Locations

Arm

Duration (Months)

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
T Cell Non-Hodgkin's Lymphoma	Drug: Chidamide Drug: Cyclophosphamide Drug: Epirubicin Drug: Vindesine Drug: Etoposide Drug: Prednisone	Phase 1/Phase 2

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Mar 1, 2016

Anticipated Primary Completion Date :

Mar 1, 2020

Anticipated Study Completion Date :

Mar 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: C-CHOEP experimental arm will be treated by Chidamide combined CHOEP ( cyclophosphamide, epirubicine, vindesine, etoposide and prednisone) regimen for 6 cycles.	Drug: Chidamide 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. Other Names: epidaza Drug: Cyclophosphamide Cyclophosphamide(750mg/m2) was administered intravenously on d1 Drug: Epirubicin epirubicin (70mg/m2)was administered intravenously on d1; Drug: Vindesine vindesine (4mg)was administered intravenously on d1; Drug: Etoposide etoposide (100mg) was administered intravenously on d1,2,3. Drug: Prednisone prednisone (60mg/m2)was administered intravenously by oral d1-5.

Arm

Intervention/Treatment

Experimental: C-CHOEP

experimental arm will be treated by Chidamide combined CHOEP ( cyclophosphamide, epirubicine, vindesine, etoposide and prednisone) regimen for 6 cycles.

Drug: Chidamide

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.

Other Names:

epidaza

Drug: Cyclophosphamide

Cyclophosphamide(750mg/m2) was administered intravenously on d1

Drug: Epirubicin

epirubicin (70mg/m2)was administered intravenously on d1;

Drug: Vindesine

vindesine (4mg)was administered intravenously on d1;

Drug: Etoposide

etoposide (100mg) was administered intravenously on d1,2,3.

Drug: Prednisone

prednisone (60mg/m2)was administered intravenously by oral d1-5.

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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 Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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