A Phase I/II Study of ASTX660 in Patients With Relapsed or Refractory T-cell Lymphoma

Sponsor

Otsuka Pharmaceutical Co., Ltd. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04362007

Collaborator

(none)

Enrollment

Location

Arms

49.6

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Relapsed or Refractory Peripheral T-cell Lymphoma(PTCL),Cutaneous T-cell Lymphoma(CTCL),Adult T-cell Leukemia/Lymphoma(ATLL)	Drug: ASTX660 Drug: ASTX660 Drug: ASTX660	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

61 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I/II, Multicenter, Open-Label, Nonrandomized Study to Evaluate the Tolerability and Safety of ASTX660 and the Efficacy at the Recommended Dose of ASTX660 in Patients With Relapsed or Refractory T-Cell Lymphoma

Actual Study Start Date :

Jul 14, 2020

Anticipated Primary Completion Date :

Sep 1, 2024

Anticipated Study Completion Date :

Sep 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 1 dose-escalation part Subjects with r/r PTCL and r/r CTCL will receive ASTX660 once a day for 7 consecutive days every other week of each 28-day cycle (ie, [7 days on/ 7 days off] ×2; daily dosing on Days 1-7 and 15-21). The starting dose will be escalated stepwise in successive cohorts of 3 to 6 evaluable subjects each (standard 3+3 study design), until the RD is determined.	Drug: ASTX660 Treatment of ASTX660 for r/r PTCL and r/r CTCL
Experimental: Phase 1 ATLL expansion part Subjects with r/r ATLL will receive ASTX660 at RD obtained from the Phase 1 part (dose-escalation part) once a day for 7 consecutive days every other week of each 28-day cycle.	Drug: ASTX660 Treatment of ASTX660 for r/r ATLL
Experimental: Phase 2 Subjects with r/r PTCL will receive ASTX660 at RD obtained from the Phase 1 part (dose-escalation part) once a day for 7 consecutive days every other week of each 28-day cycle.	Drug: ASTX660 Treatment of ASTX660 for r/r PTCL

Arm

Intervention/Treatment

Experimental: Phase 1 dose-escalation part

Subjects with r/r PTCL and r/r CTCL will receive ASTX660 once a day for 7 consecutive days every other week of each 28-day cycle (ie, [7 days on/ 7 days off] ×2; daily dosing on Days 1-7 and 15-21). The starting dose will be escalated stepwise in successive cohorts of 3 to 6 evaluable subjects each (standard 3+3 study design), until the RD is determined.

Drug: ASTX660

Treatment of ASTX660 for r/r PTCL and r/r CTCL

Experimental: Phase 1 ATLL expansion part

Subjects with r/r ATLL will receive ASTX660 at RD obtained from the Phase 1 part (dose-escalation part) once a day for 7 consecutive days every other week of each 28-day cycle.

Drug: ASTX660

Treatment of ASTX660 for r/r ATLL

Experimental: Phase 2

Subjects with r/r PTCL will receive ASTX660 at RD obtained from the Phase 1 part (dose-escalation part) once a day for 7 consecutive days every other week of each 28-day cycle.

Drug: ASTX660

Treatment of ASTX660 for r/r PTCL

Outcome Measures

Primary Outcome Measures

Safety (Phase 1 dose-escalation part) - number of subjects with dose-limiting toxicities (DLTs), AEs, abnormal clinical laboratory values or physical exam results [Up to 25 months]
Incidence of DLTs and other adverse events (AEs)
Safety (Phase 1 ATLL expansion part) - number of subjects with AEs, abnormal clinical laboratory values or physical exam results [Up to 52 months]
Incidence of adverse events (AEs)
Efficacy (Phase 2) - antitumor activity assessed by objective response rate (ORR) [Up to 22 months]
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)

Secondary Outcome Measures

Pharmacokinetic outcome of concentration-time curve (AUC) [Up to 52 months]
Assessment of pharmacokinetic parameter area under the concentration-time curve (AUC).
Pharmacokinetic outcome of maximum concentration (Cmax) [Up to 52 months]
Assessment of pharmacokinetic parameter maximum concentration (Cmax).
Pharmacokinetic outcome of time to maximum concentration (Tmax) [Up to 52 months]
Assessment of pharmacokinetic parameter time to maximum concentration (Tmax).
Pharmacokinetic outcome of samples over time [Up to 52 months]
Assessment of pharmacokinetic parameter elimination half life (t½).
Pharmacokinetic outcome of clearance of drug from plasma [Up to 52 months]
Assessment of pharmacokinetic parameter clearance of drug from plasma.
Common in all parts: antitumor activity assessed by ORR [Up to 52 months]
Antitumor activity by Investigator- or subinvestigator-assessed ORR
Common in all parts: antitumor activity assessed by duration of response (DOR) [Up to 52 months]
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.
Common in all parts: antitumor activity assessed by progression free survival (PFS) [Up to 52 months]
Number of days from the start of the study treatment to disease progression or death, whichever occurs first.
Common in all parts: overall survival (OS) [Up to 52 months]
Number of days from the day the subject received the first study treatment to the date of death, regardless of cause.
Common in all parts: time to response (TTR) [Up to 52 months]
Time from the day the subject received the first study treatment to the date of the earliest assessment of complete response or partial response.
Common in all parts: time to Progerssion (TTP) [Up to 52 months]
Time from the day the subject received the first study treatment to the date of relapse.
Common in all parts: Percentage of patients who switch to transplant [Up to 52 months]
Percentage of patients who switch to transplant
Safety (Phase 2) - number of subjects with AEs, abnormal clinical laboratory values or physical exam results. [Up to 22 months]
Incidence of adverse events (AEs)
Exploratory (Phase 1 dose-escalation part) - Assessment changes in cIAP in PBMC. [Up to 22 months]
Percentage degradation of cIAP1 protein in PBMCs from baseline.

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with T-cell lymphoma with histological diagnosis based on WHO classification (2017)
Patients with evaluable lesions.
Patients with ECOG PS score of 0 or 1.
Patients with adequate organ functions as shown below.

AST and ALT ≤ 2.0 × ULN (≤ 3.0 × ULN if liver infiltration is present)
Total bilirubin ≤ 1.5 × ULN
ANC ≥ 1,000/mm3 (≥ 750/mm3 if bone marrow infiltration is present)
Platelet count 50,000/mm3 (25,000/mm3 if bone marrow infiltration is present)
Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min
Amylase and lipase ≤ 1.0 × ULN

Exclusion Criteria:

Patients with active infection requiring treatment with antibiotics, antifungals, or antivirals
Patients with heart disease that meets the followings:
LVEF of < 50% by echocardiography or MUGA scan
Congestive heart failure (NYHA classification III or IV)
Uncontrolled heart disease including unstable angina pectoris or hypertension considered to require hospitalization within last 3 months (90 days)
Complete left bundle branch block, III degree (complete) atrioventricular block, use of pacemaker, history or complication of poorly controlled arrhythmia requiring treatment
History or complication of long QT syndrome
History or complication of ventricular arrhythmia requiring active treatment
Corrected QT interval of ≥ 470 msec based on 12-lead ECG performed at the screening
Concern on increased cardiac risk by participating in the study based on medical judgment
Patients receiving the following treatment for the primary disease prior to the initial dose of study drug
Chemotherapy or radiotherapy within last 3 weeks
Skin directed therapy including local treatment or phototherapy within last 3 weeks
Treatment with monoclonal antibody within last 4 weeks
Treatment with other study drugs or study treatment within last 3 weeks or 5 half-lives, whichever is longer
Patients with prior allogeneic stem cell transplantation, or autologous stem cell transplantation within 14 weeks prior to the day of initial dose of study drug
Patients who have received corticosteroids at a dose exceeding a prednisone equivalent dose of 10 mg/day within 3 weeks prior to the initial dose of study drug.
Patients with Inadequately controlled diabetes mellitus