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

NCT04362007 | Terminated Phase 1 Results DMC

• 2 other identifiers: 401-102-00001JapicCTI-205258
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Relapsed or Refractory Peripheral T-cell Lymphoma(PTCL),Cutaneous T-cell Lymphoma(CTCL),Adult T-cell Leukemia/Lymphoma(ATLL)

Outcome Measures

Primary Outcomes (1)

• Safety (Phase 1 Dose-escalation Part) - Number of Subjects With Dose-limiting Toxicities (DLTs), AEs, Abnormal Clinical Laboratory Values or Physical Exam Results

  Dose-limiting toxicities were defined as AEs occurring during this period that meet any of the following criteria, were not related to the primary disease, complication(s), or concomitant medication(s), and has a reasonable relationship with ASTX660. The Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) was used to determine severity. 1. Grade 4 thrombocytopenia, Grade 3 or higher clinically significant bleeding, or anemia requiring a new erythrocyte transfusion 2. Febrile neutropenia that does not resolve within 3 days or Grade 4 neutropenia that lasts for more than 7 days under appropriate treatment 3. Liver-associated abnormalities 4. Excepting the above AEs, any other Grade 3 or higher nonhematologic or Grade 4 hematologic toxicity except Grade 3 nausea, vomiting, or diarrhea lasting less than 48 hours

  28 days (Day1 to Day29)

Secondary Outcomes (5)

• Pharmacokinetic Outcome of Concentration-time Curve (AUC)

  Day1: pre-dose, 0.5, 1, 2, 3, 5, 6, 8, 24hours post-dose, Day7: pre-dose, 0.5, 1, 2, 3, 5, 6, 8, 24, 48, 72 hours post-dose

• Pharmacokinetic Outcome of Maximum Concentration (Cmax)

  Day1: pre-dose, 0.5, 1, 2, 3, 5, 6, 8, 24hours post-dose, Day7: pre-dose, 0.5, 1, 2, 3, 5, 6, 8, 24, 48, 72 hours post-dose

• Pharmacokinetic Outcome of Time to Maximum Concentration (Tmax)

  Day1: pre-dose, 0.5, 1, 2, 3, 5, 6, 8, 24hours post-dose, Day7: pre-dose, 0.5, 1, 2, 3, 5, 6, 8, 24, 48, 72 hours post-dose

• Pharmacokinetic Outcome of Elimination Half Life (t½)

  Day1: pre-dose, 0.5, 1, 2, 3, 5, 6, 8, 24hours post-dose, Day7: pre-dose, 0.5, 1, 2, 3, 5, 6, 8, 24, 48, 72 hours post-dose

• Pharmacokinetic Outcome of Clearance of Drug From Plasma

  Day1: pre-dose, 0.5, 1, 2, 3, 5, 6, 8, 24hours post-dose, Day7: pre-dose, 0.5, 1, 2, 3, 5, 6, 8, 24, 48, 72 hours post-dose

Study Arms (3)

Phase 1 dose-escalation part

EXPERIMENTAL

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

Phase 1 ATLL expansion part

EXPERIMENTAL

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

Phase 2

EXPERIMENTAL

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

Interventions

ASTX660 DRUG

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

Phase 1 dose-escalation part

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Otsuka Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Yamagata University Hospital

Yamagata, Japan

Location

MeSH Terms

Conditions

Recurrence; Lymphoma

Interventions

ASTX-660

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Director of Clinical Trials
• Organization: Otsuka Pharmaceutical Co., Ltd.

CL_OPCJ_RDA_Team@otsuka.jp

+81-3-6361-7366

Study Officials

• Nobuhito Sanada

  Otsuka Pharmaceutical Co., Ltd.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2020
• First Posted: April 24, 2020
• Study Start: July 14, 2020
• Primary Completion: November 30, 2024
• Study Completion: November 30, 2024
• Last Updated: February 25, 2026
• Results First Posted: February 25, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1)