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

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

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 Overview

• Status: Active, not recruiting
• Conditions: Relapsed or Refractory Peripheral T-cell Lymphoma(PTCL),Cutaneous T-cell Lymphoma(CTCL),Adult T-cell Leukemia/Lymphoma(ATLL)
• Intervention / Treatment: Drug: ASTX660; Drug: ASTX660; Drug: ASTX660

• Study Type: Interventional
• Enrollment (Estimated): 61
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Japan
  • Yamagata, Japan
    • Yamagata University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with T-cell lymphoma with histological diagnosis based on WHO classification (2017)
2. Patients with evaluable lesions.
3. Patients with ECOG PS score of 0 or 1.

4. 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:

1. Patients with active infection requiring treatment with antibiotics, antifungals, or antivirals

2. Patients with heart disease that meets the followings:

   1. LVEF of < 50% by echocardiography or MUGA scan
   2. Congestive heart failure (NYHA classification III or IV)
   3. Uncontrolled heart disease including unstable angina pectoris or hypertension considered to require hospitalization within last 3 months (90 days)
   4. Complete left bundle branch block, III degree (complete) atrioventricular block, use of pacemaker, history or complication of poorly controlled arrhythmia requiring treatment
   5. History or complication of long QT syndrome
   6. History or complication of ventricular arrhythmia requiring active treatment
   7. Corrected QT interval of ≥ 470 msec based on 12-lead ECG performed at the screening
   8. Concern on increased cardiac risk by participating in the study based on medical judgment

3. Patients receiving the following treatment for the primary disease prior to the initial dose of study drug

   1. Chemotherapy or radiotherapy within last 3 weeks
   2. Skin directed therapy including local treatment or phototherapy within last 3 weeks
   3. Treatment with monoclonal antibody within last 4 weeks
   4. Treatment with other study drugs or study treatment within last 3 weeks or 5 half-lives, whichever is longer
4. 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
5. 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.
6. Patients with Inadequately controlled diabetes mellitus

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / 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; Drug: ASTX660; Treatment of ASTX660 for r/r ATLL; Drug: ASTX660; Treatment of ASTX660 for r/r PTCL
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 PTCL and r/r CTCL; Drug: ASTX660; Treatment of ASTX660 for r/r ATLL; Drug: ASTX660; Treatment of ASTX660 for r/r PTCL
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 and r/r CTCL; Drug: ASTX660; Treatment of ASTX660 for r/r ATLL; Drug: ASTX660; Treatment of ASTX660 for r/r PTCL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Up to 25 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)	Up to 52 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)	Up to 22 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic outcome of concentration-time curve (AUC)	Assessment of pharmacokinetic parameter area under the concentration-time curve (AUC).	Up to 52 months
Pharmacokinetic outcome of maximum concentration (Cmax)	Assessment of pharmacokinetic parameter maximum concentration (Cmax).	Up to 52 months
Pharmacokinetic outcome of time to maximum concentration (Tmax)	Assessment of pharmacokinetic parameter time to maximum concentration (Tmax).	Up to 52 months
Pharmacokinetic outcome of samples over time	Assessment of pharmacokinetic parameter elimination half life (t½).	Up to 52 months
Pharmacokinetic outcome of clearance of drug from plasma	Assessment of pharmacokinetic parameter clearance of drug from plasma.	Up to 52 months
Common in all parts: antitumor activity assessed by ORR	Antitumor activity by Investigator- or subinvestigator-assessed ORR	Up to 52 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.	Up to 52 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.	Up to 52 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.	Up to 52 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.	Up to 52 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.	Up to 52 months
Common in all parts: Percentage of patients who switch to transplant	Percentage of patients who switch to transplant	Up to 52 months
Safety (Phase 2) - number of subjects with AEs, abnormal clinical laboratory values or physical exam results.	Incidence of adverse events (AEs)	Up to 22 months
Exploratory (Phase 1 dose-escalation part) - Assessment changes in cIAP in PBMC.	Percentage degradation of cIAP1 protein in PBMCs from baseline.	Up to 22 months

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Co., Ltd.
• Investigators: Study Director: Nobuhito Sanada, Otsuka Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 14, 2020
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: April 17, 2020
• First Submitted That Met QC Criteria: April 23, 2020
• First Posted (Actual): April 24, 2020

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Hematologic Diseases; Leukemia, Lymphoid; Leukemia; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous; Leukemia, T-Cell; Leukemia-Lymphoma, Adult T-Cell
• Other Study ID Numbers: 401-102-00001; JapicCTI-205258 (Other Grant/Funding Number: Japic)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The focus of this study is a rare disease.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No