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

Diffuse Large B-cell Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02733380
• Other study ID #: HNSZLYYML-01
• Status: Recruiting
• Phase: Phase 2
• Start date: May 2016
• Est. completion date: May 2021

Study information

• Verified date: August 2018
• Source: Henan Cancer Hospital
• Contact: Yanyan Liu, M.D. Ph.D
• Phone: +8613818176375
• Email: yyliu[@]zzu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: May 2021
• Est. primary completion date: May 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Diagnosed as diffuse large B-cell Lymphoma based on the 2008 WHO classification of tumors of haematopoietic and lymphoid tissues

2. Failed with second-line therapy

3. Having at least one measurable lesions

4. Age between 18 to 75 years old

5. World health organization-Eastern Cooperative Oncology Group Performance Status (ECOG) 0-1

6. Neutrophils more than 1.5*10^9/L; Platelets more than 90*10^9/L Hemoglobin: more than 90g/L.

7. Life expectancy no less than 3 months

8. No receiving chemotherapy in 4 weeks before enrollment

9. Agreeing to sign the written informed consents

Exclusion Criteria:

1. Pregnant ,lactating and patients at reproductive age who refuse to practice contraception

2. 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.

3. Organ transplant recipients

4. Active bleeding

5. Thrombus,embolism,cerebral hemorrhage,cerebral infarction

6. Important organ operation in less than 6 weeks

7. 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

8. Mental illness or unable to sign the informed consent

9. Drug addiction history or alcoholism which may interfere the experimental results.

10. Researchers determine unsuited to participate in this trial

11. Known allergy to any kind of study drugs

Related Conditions & MeSH terms

• Diffuse Large B-cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Chidamide
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
• Vinorelbine
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
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
10mg/m2 , IV on day 1-5 of each 14 day cycle until disease progression or unacceptable toxicity develops, up to 12 cycles
• Thalidomide
100mg,Oral at night on each day until disease progression or unacceptable toxicity develops, up to 24 weeks

Locations

Country	Name	City	State
China	Henan Cancer Hospital/The affiliated Cancer Hospital of ZhengZhou university	ZhengZhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Henan Cancer Hospital

Country where clinical trial is conducted

China, 

References & Publications (12)

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; — View 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 — View 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. — View 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. Review. — View 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. Review. — View 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, Smailu — View 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 cyt — View 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 gene — View 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. — View 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. Review. — View Citation

Wynder EL. Listen to nature. The challenge of lifestyle medicine. Soz Praventivmed. 1991;36(3):137-46. Review. — View 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 M — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	duration of response	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