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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| progression-free survival | from date of first day of treatment to the date of first documented | from the day of treatment to the date of first documented progression，up to 1 year after last patient's enrollment |
| duration of response |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yanyan Liu, M.D. Ph.D | Contact | +8613818176375 | yyliu@zzu.edu.cn | |
| Jiuyang Zhang, Master | Contact | +8615003810435 | zhangjiuyang9103@163.com |
| Name | Affiliation | Role |
|---|---|---|
| Yanyan Liu, M.D. Ph.D | Henan Cancer Hospital | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Henan Cancer Hospital/The affiliated Cancer Hospital of ZhengZhou university | Recruiting | Zhengzhou | Henan | 450008 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 1950172 | Result | Wynder EL. Listen to nature. The challenge of lifestyle medicine. Soz Praventivmed. 1991;36(3):137-46. doi: 10.1007/BF01352692. | |
| 18824292 | Result | 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. |
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| ID | Term |
|---|---|
| D016403 | Lymphoma, Large B-Cell, Diffuse |
| D012008 | Recurrence |
| ID | Term |
|---|---|
| D016393 | Lymphoma, B-Cell |
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| C547816 | N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide |
| D000077235 | Vinorelbine |
| C506643 | liposomal doxorubicin |
| D008942 | Mitoxantrone |
| D003907 | Dexamethasone |
| D013792 | Thalidomide |
| ID | Term |
|---|---|
| D014748 | Vinca Alkaloids |
| D046948 | Secologanin Tryptamine Alkaloids |
| D026121 | Indole Alkaloids |
| D000470 | Alkaloids |
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| Vinorelbine | Drug | 20mg/m2， IV on day 1 of each 14 day cycle until disease progression or unacceptable toxicity develops, up to 12 cycles |
|
| 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 |
|
| 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 |
|
| Thalidomide | Drug | 100mg,Oral at night on each day until disease progression or unacceptable toxicity develops, up to 24 weeks |
|
from the first day of documented response to disease progression or death.
| from the day of first documented response to first documented progression or death，up to 1 year after last patient's enrollment |
| 18213528 | Result | 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. |
| 21390126 | Result | 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. |
| 21796119 | Result | 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. |
| 25652253 | Result | 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. |
| 22362161 | 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. |
| 22080169 | 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. |
| 22339555 | 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. |
| 24721323 | 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. |
| 25712263 | Result | 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. |
| 20686505 | Result | 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. |
| D009369 |
| Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006571 |
| Heterocyclic Compounds |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D054836 | Indolizidines |
| D007212 | Indolizines |
| D000880 | Anthraquinones |
| D000095322 | Anthrones |
| D000873 | Anthracenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011809 | Quinones |
| D011083 | Polycyclic Compounds |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D013259 | Steroids, Fluorinated |
| D010797 | Phthalimides |
| D010795 | Phthalic Acids |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D010881 | Piperidones |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D054833 | Isoindoles |