The purpose of this dose-escalation study is to assess the safety and tolerability of treatment with Chiauranib and Chidamide administered orally over a range of doses in patients with relapsed or refractory non-Hodgkin's lymphoma, in the meantime, exploring the pharmacodynamic profile and latent biomarkers accompany with Chiauranib and Chidamide , as well as the relevancy of which and clinical benefit.
The purpose of this study is to assess the tolerability and safety include adverse events, vital signs, laboratory tests ,etc., of a range of doses of Chiauranib and Chidamide in patients with relapsed or refractory non-Hodgkin's lymphoma, and to determine the dose limit toxicity and the maximum tolerable dose. In the meantime, exploring the pharmacodynamic profile and latent biomarkers accompany with Chiauranib and Chidamide , as well as the relevancy of which and clinical benefit.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
In the lead-in period, patients take 50mg Chiauranib capsules on the forth day . In the subsequent treatment cycles, Chiauranib capsules are given orally once daily, 28 days as a cycle.
In the lead-in period, patients take a single dose of Chidamide tablet on the first day and then off for 3 days before the first cycle begins. In the subsequent treatment cycles, Chidamide tablets are given orally on Day 1,4,8,11,15,18,22 and 25 of each cycle. 28 days as a cycle
Beijing Cancer Hospital
Beijing, Beijing Municipality, China
dose-limiting toxicity (DLT)
Time frame: Day 1 - 28
Area under the concentration versus time curve (AUC)
pharmacokinetic profile of Chiauranib in combination with Chidamide
Time frame: Day 1 of the lead-in period and Day 1 of the combination therapy
Peak plasma concentration (Cmax)
pharmacokinetic profile of Chiauranib in combination with Chidamide
Time frame: Day 1 of the lead-in period and Day 1 of the combination therapy
Time of Cmax (Tmax)
pharmacokinetic profile of Chiauranib in combination with Chidamide
Time frame: Day 1 of the lead-in period and Day 1 of the combination therapy
Objective response rate
Time frame: About 21 weeks
complete response rate
Time frame: About 21 weeks
disease control rate
Time frame: About 21 weeks
time to progression
duration from date of treatment until the date of first documented progression
Time frame: About 21 weeks
Progression free survival
From date of treatment until the date of first documented progression or date of death from any cause, whichever came first
Time frame: About 21 weeks
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Duration of response
From the first date of response until the date of first documented progression
Time frame: About 21 weeks
Adverse events
Number of participants with treatment-related adverse events according to CTCAE V4.03
Time frame: About 21 weeks
Any single mutation of oncogene and copy number variation in ctDNA(single gene analysis)
Time frame: day -1 of therapy
Mutation of polygene and copy number variation in signal pathway(multi-gene analysis)
Time frame: day -1 of therapy