Clinical trial NCT02987244: Chidamide Plus CHOEP Combined With Upfront ASCT in Untreated Peripheral T-cell Lymphoma
Official title: Chidamide Plus CHOEP Combined With Upfront ASCT in Untreated Peripheral T-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: T Cell Non-Hodgkin's Lymphoma
Keywords: Chidamide, T Cell Non-Hodgkin's Lymphoma
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
Collaborators: name: Chinese PLA General Hospital
name: Peking University First Hospital
name: Peking University Third Hospital
name: Peking University Cancer Hospital & Institute
name: Tianjin Medical University Cancer Institute and Hospital
First posted: 2016-12-08
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: 2 years progression-free survival
timeFrame: the overall time frame is up to 48 months
Secondary outcomes:
measure: 5 years overall survival（OS）
timeFrame: the overall time frame is up to 84 months
measure: overall response rate(ORR) and complete remission rate(CR）
timeFrame: the overall time frame is up to 30 months
measure: adverse events
timeFrame: the overall time frame is up to 84 months
Other outcomes:
measure: maximum tolerated dose of chidamide
timeFrame: the overall time frame is up to 6 months
Locations:
city: Beijing
country: China
facility: Peking Union medical college hospital
state: Beijing
city: Tianjin
country: China
facility: Tianjin medical universty cancer institute & hospital
state: Tianjin
Study officials:
affiliation: Peking Union Medical College Hospital
name: Daobin Zhou, M.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. Epub 2012 Feb 24.
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. Epub 2015 Jun 23.
citation: Zhang Y, Zhang W, Li J, Duan M, Han B, Zhu T, Zhuang J, Cai H, Cao X, Chen M, Zhou D. Gemcitabine, cisplatin, and dexamethasone (GDP) in combination with methotrexate and pegaspargase is active in newly diagnosed peripheral T cell lymphoma patients: a phase 2, single-center, open-label study in China. Ann Hematol. 2019 Jan;98(1):143-150. doi: 10.1007/s00277-018-3488-1. Epub 2018 Sep 12.