Chidamide Combined With VDDT Regimen in the Relapse and Refractory Diffuse Large B Cell Lymphoma

NCT02733380 | Unknown Phase 2 DMC

• 1 other identifier: HNSZLYYML-01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective phase II clinical trial to observe the efficacy and safety of Chidamide combined with VDDT(vinorelbine，liposomal doxorubicin，dexamethasone and thalidomide) in relapsed and refractory patients with diffuse large B-cell lymphoma(DLBCL).

Conditions

Diffuse Large B-cell Lymphoma

Keywords

Diffuse Large B-Cell Lymphoma; Relapsed and refractory; Histone deacetylase inhibitor; Chidamide

Outcome Measures

Primary Outcomes (4)

• objective response rate

  the total proportion of patients with complete response（CR or CRu）and partial response（PR）

  every 8 weeks until 1 year after last patient's enrollment

• adverse events

  any unfavorable and unintended sign , symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure

  from the date of first cycle of treatment to 1 year after last patient's enrollment

• abnormal laboratory examinations

  includes type, incidence, relationship with treatment and severity of abnormal laboratory examinations.

  from the date of first enrollment to 1 year after last patient's enrollment

• incidence and relationship with study drugs of grade 3-4 adverse events and abnormal laboratory examinations

  the incidence and relationship with study drugs of grade 3 or 4 adverse events (based on NCI CTC-AE v4.03) and abnormal laboratory examinations

  from the date of first cycle of treatment to 1 year after last patient's enrollment

Secondary Outcomes (2)

• progression-free survival

  from the day of treatment to the date of first documented progression，up to 1 year after last patient's enrollment

• duration of response

  from the day of first documented response to first documented progression or death，up to 1 year after last patient's enrollment

Study Arms (1)

Chidamide combined with VDDT regimen

EXPERIMENTAL

Chidamide 30mg，Oral twice a week with an interval of no less than 3 days combined with regimen：VDDT（Vinorelbine，Liposomal doxorubicin or mitoxantrone ，Dexamethasone and Thalidomide）：repeated every 14 days ，up to 12 cycles

Drug: Chidamide; Drug: Vinorelbine; Drug: Liposomal Doxorubicin or mitoxantrone; Drug: Dexamethasone; Drug: Thalidomide

Interventions

Chidamide DRUG

30mg , Oral twice a week(with an interval of no less than 3 days,;e.g. Monday and Thursday，Tuesday and Friday) until disease progression or unacceptable toxicity develops

Chidamide combined with VDDT regimen

Vinorelbine DRUG

20mg/m2， IV on day 1 of each 14 day cycle until disease progression or unacceptable toxicity develops, up to 12 cycles

Chidamide combined with VDDT regimen

Liposomal Doxorubicin or mitoxantrone DRUG

20mg/m2, IV on day 1 of each 14 day cycle（Note：for patients who can not afford the liposomal doxorubicin，may be replaced into mitoxantrone 8mg/m2, IV on day1 of each 14 day cycle） until disease progression or unacceptable toxicity develops, up to 12 cycles

Chidamide combined with VDDT regimen

Dexamethasone DRUG

10mg/m2 , IV on day 1-5 of each 14 day cycle until disease progression or unacceptable toxicity develops, up to 12 cycles

Chidamide combined with VDDT regimen

Thalidomide DRUG

100mg,Oral at night on each day until disease progression or unacceptable toxicity develops, up to 24 weeks

Chidamide combined with VDDT regimen

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed as diffuse large B-cell Lymphoma based on the 2008 WHO classification of tumors of haematopoietic and lymphoid tissues
• Failed with second-line therapy
• Having at least one measurable lesions
• Age between 18 to 75 years old
• World health organization-Eastern Cooperative Oncology Group Performance Status (ECOG) 0-1
• Neutrophils more than 1.5\*10\^9/L; Platelets more than 90\*10\^9/L Hemoglobin: more than 90g/L.
• Life expectancy no less than 3 months
• No receiving chemotherapy in 4 weeks before enrollment
• Agreeing to sign the written informed consents

You may not qualify if:

• Pregnant ，lactating and patients at reproductive age who refuse to practice contraception
• QTc prolonging \>450ms，ventricular tachycardia，atrial fibrillation，cardiac conduction block， myocardial infarction in less than 1 year， congestive heart failure，coronary heart disease which needs medication.
• Organ transplant recipients
• Active bleeding
• Thrombus，embolism，cerebral hemorrhage，cerebral infarction
• Important organ operation in less than 6 weeks
• Abnormal liver function（Note：total bilirubin \>1.5 times the upper limit of normal，AST or ALT \>2.5 times the upper limit of normal （Note：5 times the upper limit of normal for patients with liver involvement）），abnormal renal function（Note：serum creatinine \>1.5 times the upper limit of normal），fluid and electrolyte disorders
• Mental illness or unable to sign the informed consent
• Drug addiction history or alcoholism which may interfere the experimental results.
• Researchers determine unsuited to participate in this trial
• Known allergy to any kind of study drugs

Sponsors & Collaborators

• Henan Cancer Hospital: lead

Study Sites (1)

Henan Cancer Hospital/The affiliated Cancer Hospital of ZhengZhou university

Zhengzhou, Henan, 450008, China

RECRUITING

Related Publications (12)

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• Morin RD, Mendez-Lago M, Mungall AJ, Goya R, Mungall KL, Corbett RD, Johnson NA, Severson TM, Chiu R, Field M, Jackman S, Krzywinski M, Scott DW, Trinh DL, Tamura-Wells J, Li S, Firme MR, Rogic S, Griffith M, Chan S, Yakovenko O, Meyer IM, Zhao EY, Smailus D, Moksa M, Chittaranjan S, Rimsza L, Brooks-Wilson A, Spinelli JJ, Ben-Neriah S, Meissner B, Woolcock B, Boyle M, McDonald H, Tam A, Zhao Y, Delaney A, Zeng T, Tse K, Butterfield Y, Birol I, Holt R, Schein J, Horsman DE, Moore R, Jones SJ, Connors JM, Hirst M, Gascoyne RD, Marra MA. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature. 2011 Jul 27;476(7360):298-303. doi: 10.1038/nature10351.

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  PMID: 25652253 RESULT

• 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.

  PMID: 22362161 RESULT

• Ning ZQ, Li ZB, Newman MJ, Shan S, Wang XH, Pan DS, Zhang J, Dong M, Du X, Lu XP. Chidamide (CS055/HBI-8000): a new histone deacetylase inhibitor of the benzamide class with antitumor activity and the ability to enhance immune cell-mediated tumor cell cytotoxicity. Cancer Chemother Pharmacol. 2012 Apr;69(4):901-9. doi: 10.1007/s00280-011-1766-x. Epub 2011 Nov 12.

  PMID: 22080169 RESULT

• Gong K, Xie J, Yi H, Li W. CS055 (Chidamide/HBI-8000), a novel histone deacetylase inhibitor, induces G1 arrest, ROS-dependent apoptosis and differentiation in human leukaemia cells. Biochem J. 2012 May 1;443(3):735-46. doi: 10.1042/BJ20111685.

  PMID: 22339555 RESULT

• Zhou Y, Pan DS, Shan S, Zhu JZ, Zhang K, Yue XP, Nie LP, Wan J, Lu XP, Zhang W, Ning ZQ. Non-toxic dose chidamide synergistically enhances platinum-induced DNA damage responses and apoptosis in Non-Small-Cell lung cancer cells. Biomed Pharmacother. 2014 May;68(4):483-91. doi: 10.1016/j.biopha.2014.03.011. Epub 2014 Mar 18.

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MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Recurrence

Interventions

N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide; Vinorelbine; liposomal doxorubicin; Mitoxantrone; Dexamethasone; Thalidomide

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Polycyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Isoindoles

Study Officials

• Yanyan Liu, M.D. Ph.D

  Henan Cancer Hospital

  STUDY DIRECTOR

Central Study Contacts

Yanyan Liu, M.D. Ph.D

CONTACT

+8613818176375; yyliu@zzu.edu.cn

Jiuyang Zhang, Master

CONTACT

+8615003810435; zhangjiuyang9103@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: director

Study Record Dates

• First Submitted: March 25, 2016
• First Posted: April 11, 2016
• Study Start: May 1, 2016
• Primary Completion: May 1, 2020
• Study Completion: May 1, 2021
• Last Updated: April 1, 2020

Record last verified: 2018-08

Locations

CN (1)