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

T Cell Non-Hodgkin's Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02987244
• Other study ID #: PUMCH-NHL-002
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: December 2, 2016
• Last updated: December 6, 2016
• Start date: March 2016
• Est. completion date: March 2023

Study information

• Verified date: December 2016
• Source: Peking Union Medical College Hospital
• Contact: Wei Zhang, M.D
• Phone: +86 136 8147 3557
• Email: vv1223[@]vip.sina.com
• Is FDA regulated: No
• Health authority: China: National Health and Family Planning Commission
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: March 2023
• Est. primary completion date: March 2020
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Peripheral
• T Cell Non-Hodgkin's Lymphoma

Intervention

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.
• Cyclophosphamide
Cyclophosphamide(750mg/m2) was administered intravenously on d1
• Epirubicin
epirubicin (70mg/m2)was administered intravenously on d1;
• Vindesine
vindesine (4mg)was administered intravenously on d1;
• Etoposide
etoposide (100mg) was administered intravenously on d1,2,3.
• Prednisone
prednisone (60mg/m2)was administered intravenously by oral d1-5.

Locations

Country	Name	City	State
China	Peking Union medical college hospital	Beijing	Beijing
China	Tianjin medical universty cancer institute & hospital	Tianjin	Tianjin

Sponsors (6)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital	Beijing Cancer Hospital, Chinese PLA General Hospital, Peking University First Hospital, Peking University Third Hospital, Tianjin Medical University Cancer Institute and Hospital

Country where clinical trial is conducted

China, 

References & Publications (2)

Dong M, Ning ZQ, Xing PY, Xu JL, Cao HX, Dou GF, Meng ZY, Shi YK, Lu XP, Feng FY. Phase I study of chidamide (CS055/HBI-8000), a new histone deacetylase inhibitor, in patients with advanced solid tumors and lymphomas. Cancer Chemother Pharmacol. 2012 Jun;69(6):1413-22. doi: 10.1007/s00280-012-1847-5. — View Citation

Shi Y, Dong M, Hong X, Zhang W, Feng J, Zhu J, Yu L, Ke X, Huang H, Shen Z, Fan Y, Li W, Zhao X, Qi J, Huang H, Zhou D, Ning Z, Lu X. Results from a multicenter, open-label, pivotal phase II study of chidamide in relapsed or refractory peripheral T-cell lymphoma. Ann Oncol. 2015 Aug;26(8):1766-71. doi: 10.1093/annonc/mdv237. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	maximum tolerated dose of chidamide	from recruiting the first 9 subjects to all of them received 1 cycle C-CHOEP regiment	the overall time frame is up to 6 months	Yes
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes