Differences Between Chidamide Taken Daily and Twice a Week in Therapeutic Effect，Pharmacokinetics, Pharmacodynamics and EB Virus Activation
Study Details
Study Description
Brief Summary
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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.
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To examine whether Chidamide could activate EB virus, and whether the above two different ways of administration are different in EB virus activation.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Chidamide BIW Chidamide is given 30mg,5mg/pill,twice a week, for at least 6 weeks |
Drug: Chidamide BIW
Chidamide is given 30mg, twice a week
Other Names:
|
| Experimental: Chidamide QD Chidamide is given 10mg,5mg/pill, everyday,for at least 6 weeks. |
Drug: Chidamide QD
Chidamide is given 10mg,QD
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Overall Response Rate (ORR) [through study completion, an average of 30 months]
- Duration of Response (DOR) [through study completion, an average of 30 months]
Secondary Outcome Measures
- Progression Free Survival (PFS) [through study completion, an average of 30 months]
- Overall Survival (OS) [through study completion, an average of 30 months]
- EBV-DNA [through study completion, an average of 30 months]
- EBV-antibodies [through study completion, an average of 30 months]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
Eligibility Criteria
Criteria
Inclusion Criteria:
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NKTCL patients confirmed by histopathology examination.
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Age 18-75 years old, male or female, fertile women should have effective contraceptive measures.
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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.
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Patients who had 1-3 regimens (including chemotherapy, stem cell transplantation), but did not achieve remission or relapsed after remission.
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With at least 1 measurable focus, whose long diameter ˃ 1.5cm, short diameter ˃1.0cm, or at least one evaluable focus.
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Body weight: male 67±20 kilograms (47-87 kg), female 55±20 kilograms (35-75 kg);
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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；
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ECOG: 0-2;
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Estimated survival ≥ 3 months;
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Willing to sign the written consent before the trial.
Exclusion Criteria:
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Women during pregnancy or lactation, or fertile women unwilling to take contraceptive measures.
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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.
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Cardiac B ultrasound show end-diastolic pericardial dark zone≥ 10cm
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Patients who have received organ transplantation.
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Patients received symptomatic treatment for bone marrow toxicity within 7 days prior to enrollment.
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Patients with active hemorrhage.
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Patients with or with history of thrombosis, embolism, cerebral hemorrhage, or cerebral infarction.
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Patients with active infection, or with continuous fever within 14 days prior to enrollment.
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Had major organ surgery within 6 weeks prior to enrollment.
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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).
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Patients with history of Chidamide treatment and had disease progression within 6 months afterward;
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Patients that received large dose of steroids (˃10mg/d dexamethasone or other steroids of the equivalent dosage) within 4 weeks prior to enrollment;
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Patients with hemophagocytic syndrome;
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Patients with central nerve system diseases or history of central nerve system diseases;
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Patients with mental disorders or those do not have the ability to consent;
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Patients that had been enrolled in other clinical trials within 3 months prior to enrollment;
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Patients with drug abuse, long term alcoholism that may impact the results of the trial.
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Non-appropriate patients for the trial according to the judgment of the investigators.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Huiqiang Huang
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Sunyat-senU201602101