Differences Between Chidamide Taken Daily and Twice a Week in Therapeutic Effect，Pharmacokinetics, Pharmacodynamics and EB Virus Activation

EBV Clinical Trial

Official title:

Research About the Differences Between Chidamide Taken Daily and Twice a Week in Pharmacokinetics

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02878278
• Other study ID #: Sunyat-senU201602101
• Status: Not yet recruiting
• Phase: Phase 2
• First received: August 20, 2016
• Last updated: August 22, 2016
• Start date: September 2016
• Est. completion date: September 2019

Study information

• Verified date: August 2016
• Source: Sun Yat-sen University
• Contact: Huiqiang Huang, Professor
• Email: huanghq[@]sysucc.org.cn
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

1. To compare the therapeutic effects, safety and the corresponding pharmacokinetics and pharmacodynamics between two different method of drug administration: 10mg, daily and 30mg/d, twice every week, and find out the more effect way of Chidamide administration.

2. To examine whether Chidamide could activate EB virus, and whether the above two different ways of administration are different in EB virus activation.

Description:

Currently, Chidamide is taken twice a week, this comes from cell experiment and phase I clinical trial, which showed that the de-acetylation effect of Chidamide could last for 72 hours after administration. However, daily administration of Chidamide may create a more steady Chidamide concentration, thus improve the de-acetylation effect of Chidamide, so it's necessary to compare the two different ways of administration.

Current study showed that Romidepsin, a HDACI, could activate EBV during the treatment of NKTCL, whether Chidamide, as a novel HDACI, could activate EBV is still not clear, so this problem is worth to be accessed.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 24
• Est. completion date: September 2019
• Est. primary completion date: March 2019
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. NKTCL patients confirmed by histopathology examination.

2. Age 18-75 years old, male or female, fertile women should have effective contraceptive measures.

3. NT/T cell lymphoma patients with disease progression or non-remission after L-asparaginase treatment or L-asparaginase-contained regimen treatment. Non-remission is defined as: patients do not have partial remission (PR) or better responses after treated by L-asparaginase contained regimen.

4. Patients who had 1-3 regimens (including chemotherapy, stem cell transplantation), but did not achieve remission or relapsed after remission.

5. With at least 1 measurable focus, whose long diameter ? 1.5cm, short diameter ?1.0cm, or at least one evaluable focus.

6. Body weight: male 67±20 kilograms (47-87 kg), female 55±20 kilograms (35-75 kg);

7. Blood-routine test within 14 days of enrollment should satisfy (except lymphoma-related abnormalities): Hb=80g/L,ANC=1.0×109/L,PLT=75×109/L;

8. ECOG: 0-2;

9. Estimated survival = 3 months;

10. Willing to sign the written consent before the trial.

Exclusion Criteria:

1. Women during pregnancy or lactation, or fertile women unwilling to take contraceptive measures.

2. QTc elongation with clinical significance ( male? 450ms, female? 470ms), ventricular tachycardia, atrial fibrillation, cardiac conducting blockage, myocardial infarction within 1 year, congestive heart failure, symptomatic coronary heart disease that requires treatment.

3. Cardiac B ultrasound show end-diastolic pericardial dark zone= 10cm

4. Patients who have received organ transplantation.

5. Patients received symptomatic treatment for bone marrow toxicity within 7 days prior to enrollment.

6. Patients with active hemorrhage.

7. Patients with or with history of thrombosis, embolism, cerebral hemorrhage, or cerebral infarction.

8. Patients with active infection, or with continuous fever within 14 days prior to enrollment.

9. Had major organ surgery within 6 weeks prior to enrollment.

10. Abnormal blood routine test results within 14 days prior to enrollment (Hb?80g/L,ANC?1.0×109/L,PLT?75×109/L; Impaired liver function ( Total bilirubin ? 1.5 times of normal maximum, ALT/AST? 2.5 times of normal maximum, for patients with infiltrative liver disease ALT/AST ? 5 times of normal maximum), impaired renal function (serum creatinin? 1.5 times of normal maximum).

11. Patients with history of Chidamide treatment and had disease progression within 6 months afterward;

12. Patients that received large dose of steroids (?10mg/d dexamethasone or other steroids of the equivalent dosage) within 4 weeks prior to enrollment;

13. Patients with hemophagocytic syndrome;

14. Patients with central nerve system diseases or history of central nerve system diseases;

15. Patients with mental disorders or those do not have the ability to consent;

16. Patients that had been enrolled in other clinical trials within 3 months prior to enrollment;

17. Patients with drug abuse, long term alcoholism that may impact the results of the trial.

18. Non-appropriate patients for the trial according to the judgment of the investigators.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• EBV
• Lymphoma, Extranodal NK-T-Cell

Intervention

Drug:
• Chidamide BIW
Chidamide is given 30mg, twice a week
• Chidamide QD
Chidamide is given 10mg,QD

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Huiqiang Huang

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (ORR)		through study completion, an average of 30 months	No
Primary	Duration of Response (DOR)		through study completion, an average of 30 months	No
Secondary	Progression Free Survival (PFS)		through study completion, an average of 30 months	No
Secondary	Overall Survival (OS)		through study completion, an average of 30 months	No
Secondary	EBV-DNA		through study completion, an average of 30 months	No
Secondary	EBV-antibodies		through study completion, an average of 30 months	No
Secondary	white blood cell count		every week though study completion,from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 30 months	Yes
Secondary	red blood cell count		every week though study completion,from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 30 months	Yes
Secondary	blood Hb level		every week though study completion,from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 30 months	Yes
Secondary	blood platelet count		every week though study completion,from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 30 months	Yes
Secondary	vital signs		every week though study completion,from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 30 months	Yes
Secondary	Serum alanine aminotransferase level		every 3 weeks though study completion,from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 30 months	Yes
Secondary	Serum aspartate transaminase level		every 3 weeks though study completion,from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 30 months	Yes
Secondary	Serum total bilirubin level		every 3 weeks though study completion,from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 30 months	Yes
Secondary	Serum direct bilirubin level		every 3 weeks though study completion,from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 30 months	Yes
Secondary	Serum indirect bilirubin level		every 3 weeks though study completion,from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 30 months	Yes
Secondary	Serum glutamyltranspeptidase level		every 3 weeks though study completion,from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 30 months	Yes
Secondary	Serum albumin level		every 3 weeks though study completion,from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 30 months	Yes
Secondary	Serum ureal nitrogen level		every 3 weeks though study completion,from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 30 months	Yes
Secondary	Serum creatinin level		every 3 weeks though study completion,from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 30 months	Yes
Secondary	fasting blood glucose level		every 3 weeks though study completion,from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 30 months	Yes
Secondary	blood electrolytes level(K+, Na+,Cl-,Ca2+,Mg2+)		every 3 weeks though study completion,from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 30 months	Yes
Secondary	blood LDH level		every 6 weeks though study completion,from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 30 months	Yes
Secondary	QTc from ECG		every 6 weeks though study completion,from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 30 months	Yes