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

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.

Study Overview

• Status: Recruiting
• Conditions: T Cell Non-Hodgkin's Lymphoma
• Intervention / Treatment: Drug: Chidamide; Drug: Cyclophosphamide; Drug: Epirubicin; Drug: Vindesine; Drug: Etoposide; Drug: Prednisone

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 Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Wei Zhang, M.D; Phone Number: +86 136 8147 3557; Email: vv1223@vip.sina.com
• Study Contact Backup: Name: Yan Zhang, M.D; Phone Number: +86 13810000485; Email: zhangyan10659@pumch.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Peking Union Medical College Hospital
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Recruiting
      • Tianjin medical universty cancer institute & hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Collaborators: Peking University First Hospital; Chinese PLA General Hospital; Peking University Third Hospital; Peking University Cancer Hospital & Institute; Tianjin Medical University Cancer Institute and Hospital
• Investigators: Principal Investigator: Daobin Zhou, M.D, Peking Union Medical College Hospital

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Anticipated): March 1, 2020
• Study Completion (Anticipated): March 1, 2023

Study Registration Dates

• First Submitted: December 2, 2016
• First Submitted That Met QC Criteria: December 6, 2016
• First Posted (Estimate): December 8, 2016

Study Record Updates

• Last Update Posted (Estimate): December 8, 2016
• Last Update Submitted That Met QC Criteria: December 6, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Chidamide, T Cell Non-Hodgkin's Lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Cyclophosphamide; Etoposide; Epirubicin; Prednisone; Vindesine
• Other Study ID Numbers: PUMCH-NHL-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO