Back to resultsChidamide Combined With VDDT Regimen in the Relapse and Refractory Diffuse Large B Cell Lymphoma
Primary Purpose
Diffuse Large B-cell Lymphoma
Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Chidamide
Vinorelbine
Liposomal Doxorubicin or mitoxantrone
Dexamethasone
Thalidomide
Sponsored by
About this trial
This is an interventional treatment trial for Diffuse Large B-cell Lymphoma focused on measuring Diffuse Large B-Cell Lymphoma, Relapsed and refractory, Histone deacetylase inhibitor, Chidamide
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Sites / Locations
- Henan Cancer Hospital/The affiliated Cancer Hospital of ZhengZhou universityRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Chidamide combined with VDDT regimen
Arm Description
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
Outcomes
Primary Outcome Measures
objective response rate
the total proportion of patients with complete response（CR or CRu）and partial response（PR）
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
abnormal laboratory examinations
includes type, incidence, relationship with treatment and severity of abnormal laboratory examinations.
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
Secondary Outcome Measures
progression-free survival
from date of first day of treatment to the date of first documented
duration of response
from the first day of documented response to disease progression or death.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02733380
Brief Title
Chidamide Combined With VDDT Regimen in the Relapse and Refractory Diffuse Large B Cell Lymphoma
Official Title
The Efficacy and Safety of Chidamide Combined With VDDT Regimen（Vinorelbine，Liposomal Doxorubicin，Dexamethasone and Thalidomide） in Relapse and Refractory Patients With Diffuse Large B Cell Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Unknown status
Study Start Date
May 2016 (undefined)
Primary Completion Date
May 2020 (Anticipated)
Study Completion Date
May 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Henan Cancer Hospital
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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).
Detailed Description
There are one third of diffuse large B-cell Lymphoma patients suffering relapse and refractory, which are the major cause of death among these patients. Vinorelbine，liposomal doxorubicin，mitoxantrone, dexamethasone and thalidomide have been used in the therapy of patients who failed with Second-line treatments in our center. This regimen is well tolerated but the effect needs to be improved. Chidamide，a histone deacetylase inhibitor has been approved for the treatment of refractory T-cell lymphoma in China. The goal is to assess the efficacy and safety of chidamide combined with VDDT（vinorelbine，liposomal doxorubicin，dexamethasone and thalidomide） in relapse and refractory patients with diffuse large B-cell Lymphoma.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large B-cell Lymphoma
Keywords
Diffuse Large B-Cell Lymphoma, Relapsed and refractory, Histone deacetylase inhibitor, Chidamide
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Chidamide combined with VDDT regimen
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Chidamide
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Vinorelbine
Intervention Description
20mg/m2， IV on day 1 of each 14 day cycle until disease progression or unacceptable toxicity develops, up to 12 cycles
Intervention Type
Drug
Intervention Name(s)
Liposomal Doxorubicin or mitoxantrone
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
10mg/m2 , IV on day 1-5 of each 14 day cycle until disease progression or unacceptable toxicity develops, up to 12 cycles
Intervention Type
Drug
Intervention Name(s)
Thalidomide
Intervention Description
100mg,Oral at night on each day until disease progression or unacceptable toxicity develops, up to 24 weeks
Primary Outcome Measure Information:
Title
objective response rate
Description
the total proportion of patients with complete response（CR or CRu）and partial response（PR）
Time Frame
every 8 weeks until 1 year after last patient's enrollment
Title
adverse events
Description
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
Time Frame
from the date of first cycle of treatment to 1 year after last patient's enrollment
Title
abnormal laboratory examinations
Description
includes type, incidence, relationship with treatment and severity of abnormal laboratory examinations.
Time Frame
from the date of first enrollment to 1 year after last patient's enrollment
Title
incidence and relationship with study drugs of grade 3-4 adverse events and abnormal laboratory examinations
Description
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
Time Frame
from the date of first cycle of treatment to 1 year after last patient's enrollment
Secondary Outcome Measure Information:
Title
progression-free survival
Description
from date of first day of treatment to the date of first documented
Time Frame
from the day of treatment to the date of first documented progression，up to 1 year after last patient's enrollment
Title
duration of response
Description
from the first day of documented response to disease progression or death.
Time Frame
from the day of first documented response to first documented progression or death，up to 1 year after last patient's enrollment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yanyan Liu, M.D. Ph.D
Phone
+8613818176375
Email
yyliu@zzu.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Jiuyang Zhang, Master
Phone
+8615003810435
Email
zhangjiuyang9103@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yanyan Liu, M.D. Ph.D
Organizational Affiliation
Henan Cancer Hospital
Official's Role
Study Director
Facility Information:
Facility Name
Henan Cancer Hospital/The affiliated Cancer Hospital of ZhengZhou university
City
ZhengZhou
State/Province
Henan
ZIP/Postal Code
450008
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yanyan Liu, M.D.
Phone
+8613838176375
Email
yyliu@zzu.edu.cn
First Name & Middle Initial & Last Name & Degree
Jiuyang Zhang, Master
Phone
+8615003810435
Email
zhangjiuyang9103@163.com
First Name & Middle Initial & Last Name & Degree
Yanyan Liu, M.D.
12. IPD Sharing Statement
Citations:
PubMed Identifier
1950172
Citation
Wynder EL. Listen to nature. The challenge of lifestyle medicine. Soz Praventivmed. 1991;36(3):137-46. doi: 10.1007/BF01352692.
Results Reference
result
PubMed Identifier
18824292
Citation
Witt O, Deubzer HE, Milde T, Oehme I. HDAC family: What are the cancer relevant targets? Cancer Lett. 2009 May 8;277(1):8-21. doi: 10.1016/j.canlet.2008.08.016. Epub 2008 Sep 27.
Results Reference
result
PubMed Identifier
18213528
Citation
Khan AN, Tomasi TB. Histone deacetylase regulation of immune gene expression in tumor cells. Immunol Res. 2008;40(2):164-78. doi: 10.1007/s12026-007-0085-0.
Results Reference
result
PubMed Identifier
21390126
Citation
Pasqualucci L, Dominguez-Sola D, Chiarenza A, Fabbri G, Grunn A, Trifonov V, Kasper LH, Lerach S, Tang H, Ma J, Rossi D, Chadburn A, Murty VV, Mullighan CG, Gaidano G, Rabadan R, Brindle PK, Dalla-Favera R. Inactivating mutations of acetyltransferase genes in B-cell lymphoma. Nature. 2011 Mar 10;471(7337):189-95. doi: 10.1038/nature09730.
Results Reference
result
PubMed Identifier
21796119
Citation
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.
Results Reference
result
PubMed Identifier
25652253
Citation
Mondello P, Younes A. Emerging drugs for diffuse large B-cell lymphoma. Expert Rev Anticancer Ther. 2015 Apr;15(4):439-51. doi: 10.1586/14737140.2015.1009042. Epub 2015 Feb 5.
Results Reference
result
PubMed Identifier
22362161
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.
Results Reference
result
PubMed Identifier
22080169
Citation
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.
Results Reference
result
PubMed Identifier
22339555
Citation
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.
Results Reference
result
PubMed Identifier
24721323
Citation
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.
Results Reference
result
PubMed Identifier
25712263
Citation
Frys S, Simons Z, Hu Q, Barth MJ, Gu JJ, Mavis C, Skitzki J, Song L, Czuczman MS, Hernandez-Ilizaliturri FJ. Entinostat, a novel histone deacetylase inhibitor is active in B-cell lymphoma and enhances the anti-tumour activity of rituximab and chemotherapy agents. Br J Haematol. 2015 May;169(4):506-19. doi: 10.1111/bjh.13318. Epub 2015 Feb 23.
Results Reference
result
PubMed Identifier
20686505
Citation
Shimizu R, Kikuchi J, Wada T, Ozawa K, Kano Y, Furukawa Y. HDAC inhibitors augment cytotoxic activity of rituximab by upregulating CD20 expression on lymphoma cells. Leukemia. 2010 Oct;24(10):1760-8. doi: 10.1038/leu.2010.157. Epub 2010 Aug 5.
Results Reference
result
Learn more about this trial
Chidamide Combined With VDDT Regimen in the Relapse and Refractory Diffuse Large B Cell Lymphoma
We'll reach out to this number within 24 hrs