Phase 1 (dose-escalation part): Investigate the tolerability and safety of ASTX660 in patients with r/r PTCL and r/r CTCL and determine the recommended dose (RD) for the Phase 2. Phase 1 (ATLL expansion part): Evaluate the safety of ASTX660 at RD in patients with r/r ATLL. Phase 2 : Evaluate the efficacy of ASTX660 at RD in patients with r/r PTCL.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
61
Yamagata University Hospital
Yamagata, Japan
Safety (Phase 1 dose-escalation part) - number of subjects with dose-limiting toxicities (DLTs), AEs, abnormal clinical laboratory values or physical exam results
Incidence of DLTs and other adverse events (AEs)
Time frame: Up to 52.6 months
Safety (Phase 1 ATLL expansion part) - number of subjects with AEs, abnormal clinical laboratory values or physical exam results
Incidence of adverse events (AEs)
Time frame: Up to 52.6 months
Efficacy (Phase 2) - antitumor activity assessed by objective response rate (ORR)
Antitumor activity by ORR by the Central Data Review Committee based on Lugano response criteria for non-Hodgkin's lymphoma by International Working Group (2014)
Time frame: Up to 52.6 months
Pharmacokinetic outcome of concentration-time curve (AUC)
Assessment of pharmacokinetic parameter area under the concentration-time curve (AUC).
Time frame: Up to Day 1 in Cycle 2 (28 days per cycle)
Pharmacokinetic outcome of maximum concentration (Cmax)
Assessment of pharmacokinetic parameter maximum concentration (Cmax).
Time frame: Up to Day 1 in Cycle 2 (28 days per cycle)
Pharmacokinetic outcome of time to maximum concentration (Tmax)
Assessment of pharmacokinetic parameter time to maximum concentration (Tmax).
Time frame: Up to Day 1 in Cycle 2 (28 days per cycle)
Pharmacokinetic outcome of samples over time
Assessment of pharmacokinetic parameter elimination half life (t½).
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: Up to Day 1 in Cycle 2 (28 days per cycle)
Pharmacokinetic outcome of clearance of drug from plasma
Assessment of pharmacokinetic parameter clearance of drug from plasma.
Time frame: Up to Day 1 in Cycle 2 (28 days per cycle)
Common in all parts: antitumor activity assessed by ORR
Antitumor activity by Investigator- or subinvestigator-assessed ORR
Time frame: Up to 52.6 months
Common in all parts: antitumor activity assessed by duration of response (DOR)
Time from the date of the earliest assessment of complete response or partial response to the date of relapse or death, whichever occurs earlier, or the last efficacy assessment date for subjects without a relapse or death.
Time frame: Up to 52.6 months
Common in all parts: antitumor activity assessed by progression free survival (PFS)
Number of days from the start of the study treatment to disease progression or death, whichever occurs first.
Time frame: Up to 52.6 months
Common in all parts: overall survival (OS)
Number of days from the day the subject received the first study treatment to the date of death, regardless of cause.
Time frame: Up to 52.6 months
Common in all parts: time to response (TTR)
Time from the day the subject received the first study treatment to the date of the earliest assessment of complete response or partial response.
Time frame: Up to 52.6 months
Common in all parts: time to Progerssion (TTP)
Time from the day the subject received the first study treatment to the date of relapse.
Time frame: Up to 52.6 months
Common in all parts: Percentage of patients who switch to transplant
Percentage of patients who switch to transplant
Time frame: Up to 52.6 months
Safety (Phase 2) - number of subjects with AEs, abnormal clinical laboratory values or physical exam results.
Incidence of adverse events (AEs)
Time frame: Up to 52.6 months
Exploratory (Phase 1 dose-escalation part) - Assessment changes in cIAP in PBMC.
Percentage degradation of cIAP1 protein in PBMCs from baseline.
Time frame: Up to 52.6 months