Back to resultsDifferences Between Chidamide Taken Daily and Twice a Week in Therapeutic Effect，Pharmacokinetics, Pharmacodynamics and EB Virus Activation
Primary Purpose
Lymphoma, Extranodal NK-T-Cell, EBV
Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Chidamide BIW
Chidamide QD
Sponsored by
About this trial
This is an interventional treatment trial for Lymphoma, Extranodal NK-T-Cell focused on measuring Chidamide, Administration method
Eligibility Criteria
Inclusion Criteria:
- NKTCL patients confirmed by histopathology examination.
- Age 18-75 years old, male or female, fertile women should have effective contraceptive measures.
- 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.
- Patients who had 1-3 regimens (including chemotherapy, stem cell transplantation), but did not achieve remission or relapsed after remission.
- With at least 1 measurable focus, whose long diameter ˃ 1.5cm, short diameter ˃1.0cm, or at least one evaluable focus.
- Body weight: male 67±20 kilograms (47-87 kg), female 55±20 kilograms (35-75 kg);
- 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；
- ECOG: 0-2;
- Estimated survival ≥ 3 months;
- Willing to sign the written consent before the trial.
Exclusion Criteria:
- Women during pregnancy or lactation, or fertile women unwilling to take contraceptive measures.
- 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.
- Cardiac B ultrasound show end-diastolic pericardial dark zone≥ 10cm
- Patients who have received organ transplantation.
- Patients received symptomatic treatment for bone marrow toxicity within 7 days prior to enrollment.
- Patients with active hemorrhage.
- Patients with or with history of thrombosis, embolism, cerebral hemorrhage, or cerebral infarction.
- Patients with active infection, or with continuous fever within 14 days prior to enrollment.
- Had major organ surgery within 6 weeks prior to enrollment.
- 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).
- Patients with history of Chidamide treatment and had disease progression within 6 months afterward;
- Patients that received large dose of steroids (˃10mg/d dexamethasone or other steroids of the equivalent dosage) within 4 weeks prior to enrollment;
- Patients with hemophagocytic syndrome;
- Patients with central nerve system diseases or history of central nerve system diseases;
- Patients with mental disorders or those do not have the ability to consent;
- Patients that had been enrolled in other clinical trials within 3 months prior to enrollment;
- Patients with drug abuse, long term alcoholism that may impact the results of the trial.
- Non-appropriate patients for the trial according to the judgment of the investigators.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Chidamide BIW
Chidamide QD
Arm Description
Chidamide is given 30mg,5mg/pill,twice a week, for at least 6 weeks
Chidamide is given 10mg,5mg/pill, everyday,for at least 6 weeks.
Outcomes
Primary Outcome Measures
Overall Response Rate (ORR)
Duration of Response (DOR)
Secondary Outcome Measures
Progression Free Survival (PFS)
Overall Survival (OS)
EBV-DNA
EBV-antibodies
white blood cell count
red blood cell count
blood Hb level
blood platelet count
vital signs
Serum alanine aminotransferase level
Serum aspartate transaminase level
Serum total bilirubin level
Serum direct bilirubin level
Serum indirect bilirubin level
Serum glutamyltranspeptidase level
Serum albumin level
Serum ureal nitrogen level
Serum creatinin level
fasting blood glucose level
blood electrolytes level（K+, Na+，Cl-，Ca2+，Mg2+）
blood LDH level
QTc from ECG
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02878278
Brief Title
Differences Between Chidamide Taken Daily and Twice a Week in Therapeutic Effect，Pharmacokinetics, Pharmacodynamics and EB Virus Activation
Official Title
Research About the Differences Between Chidamide Taken Daily and Twice a Week in Pharmacokinetics
Study Type
Interventional
2. Study Status
Record Verification Date
August 2016
Overall Recruitment Status
Unknown status
Study Start Date
September 2016 (undefined)
Primary Completion Date
March 2019 (Anticipated)
Study Completion Date
September 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Huiqiang Huang
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
To examine whether Chidamide could activate EB virus, and whether the above two different ways of administration are different in EB virus activation.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, Extranodal NK-T-Cell, EBV
Keywords
Chidamide, Administration method
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
24 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Chidamide BIW
Arm Type
Experimental
Arm Description
Chidamide is given 30mg,5mg/pill,twice a week, for at least 6 weeks
Arm Title
Chidamide QD
Arm Type
Experimental
Arm Description
Chidamide is given 10mg,5mg/pill, everyday,for at least 6 weeks.
Intervention Type
Drug
Intervention Name(s)
Chidamide BIW
Other Intervention Name(s)
Epidaza
Intervention Description
Chidamide is given 30mg, twice a week
Intervention Type
Drug
Intervention Name(s)
Chidamide QD
Other Intervention Name(s)
Epidaza
Intervention Description
Chidamide is given 10mg,QD
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Time Frame
through study completion, an average of 30 months
Title
Duration of Response (DOR)
Time Frame
through study completion, an average of 30 months
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Time Frame
through study completion, an average of 30 months
Title
Overall Survival (OS)
Time Frame
through study completion, an average of 30 months
Title
EBV-DNA
Time Frame
through study completion, an average of 30 months
Title
EBV-antibodies
Time Frame
through study completion, an average of 30 months
Title
white blood cell count
Time Frame
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
Title
red blood cell count
Time Frame
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
Title
blood Hb level
Time Frame
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
Title
blood platelet count
Time Frame
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
Title
vital signs
Time Frame
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
Title
Serum alanine aminotransferase level
Time Frame
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
Title
Serum aspartate transaminase level
Time Frame
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
Title
Serum total bilirubin level
Time Frame
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
Title
Serum direct bilirubin level
Time Frame
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
Title
Serum indirect bilirubin level
Time Frame
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
Title
Serum glutamyltranspeptidase level
Time Frame
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
Title
Serum albumin level
Time Frame
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
Title
Serum ureal nitrogen level
Time Frame
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
Title
Serum creatinin level
Time Frame
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
Title
fasting blood glucose level
Time Frame
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
Title
blood electrolytes level（K+, Na+，Cl-，Ca2+，Mg2+）
Time Frame
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
Title
blood LDH level
Time Frame
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
Title
QTc from ECG
Time Frame
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
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:
NKTCL patients confirmed by histopathology examination.
Age 18-75 years old, male or female, fertile women should have effective contraceptive measures.
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.
Patients who had 1-3 regimens (including chemotherapy, stem cell transplantation), but did not achieve remission or relapsed after remission.
With at least 1 measurable focus, whose long diameter ˃ 1.5cm, short diameter ˃1.0cm, or at least one evaluable focus.
Body weight: male 67±20 kilograms (47-87 kg), female 55±20 kilograms (35-75 kg);
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；
ECOG: 0-2;
Estimated survival ≥ 3 months;
Willing to sign the written consent before the trial.
Exclusion Criteria:
Women during pregnancy or lactation, or fertile women unwilling to take contraceptive measures.
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.
Cardiac B ultrasound show end-diastolic pericardial dark zone≥ 10cm
Patients who have received organ transplantation.
Patients received symptomatic treatment for bone marrow toxicity within 7 days prior to enrollment.
Patients with active hemorrhage.
Patients with or with history of thrombosis, embolism, cerebral hemorrhage, or cerebral infarction.
Patients with active infection, or with continuous fever within 14 days prior to enrollment.
Had major organ surgery within 6 weeks prior to enrollment.
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).
Patients with history of Chidamide treatment and had disease progression within 6 months afterward;
Patients that received large dose of steroids (˃10mg/d dexamethasone or other steroids of the equivalent dosage) within 4 weeks prior to enrollment;
Patients with hemophagocytic syndrome;
Patients with central nerve system diseases or history of central nerve system diseases;
Patients with mental disorders or those do not have the ability to consent;
Patients that had been enrolled in other clinical trials within 3 months prior to enrollment;
Patients with drug abuse, long term alcoholism that may impact the results of the trial.
Non-appropriate patients for the trial according to the judgment of the investigators.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Huiqiang Huang, Professor
Email
huanghq@sysucc.org.cn
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
The data of the trial would be accessable on the corresponding website after the trial is finished.
Learn more about this trial
Differences Between Chidamide Taken Daily and Twice a Week in Therapeutic Effect，Pharmacokinetics, Pharmacodynamics and EB Virus Activation
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