Clinical trial NCT04362007: A Phase I/II Study of ASTX660 in Patients With Relapsed or Refractory T-cell Lymphoma
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Relapsed or Refractory Peripheral T-cell Lymphoma(PTCL),Cutaneous T-cell Lymphoma(CTCL),Adult T-cell Leukemia/Lymphoma(ATLL)
Lead sponsor: Otsuka Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-04-24
Enrollment: 61
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Safety (Phase 1 dose-escalation part) - number of subjects with dose-limiting toxicities (DLTs), AEs, abnormal clinical laboratory values or physical exam results
timeFrame: Up to 52.6 months
measure: Safety (Phase 1 ATLL expansion part) - number of subjects with AEs, abnormal clinical laboratory values or physical exam results
timeFrame: Up to 52.6 months
measure: Efficacy (Phase 2) - antitumor activity assessed by objective response rate (ORR)
timeFrame: Up to 52.6 months
Secondary outcomes:
measure: Pharmacokinetic outcome of concentration-time curve (AUC)
timeFrame: Up to Day 1 in Cycle 2 (28 days per cycle)
measure: Pharmacokinetic outcome of maximum concentration (Cmax)
timeFrame: Up to Day 1 in Cycle 2 (28 days per cycle)
measure: Pharmacokinetic outcome of time to maximum concentration (Tmax)
timeFrame: Up to Day 1 in Cycle 2 (28 days per cycle)
measure: Pharmacokinetic outcome of samples over time
timeFrame: Up to Day 1 in Cycle 2 (28 days per cycle)
measure: Pharmacokinetic outcome of clearance of drug from plasma
timeFrame: Up to Day 1 in Cycle 2 (28 days per cycle)
measure: Common in all parts: antitumor activity assessed by ORR
timeFrame: Up to 52.6 months
measure: Common in all parts: antitumor activity assessed by duration of response (DOR)
timeFrame: Up to 52.6 months
measure: Common in all parts: antitumor activity assessed by progression free survival (PFS)
timeFrame: Up to 52.6 months
measure: Common in all parts: overall survival (OS)
timeFrame: Up to 52.6 months
measure: Common in all parts: time to response (TTR)
timeFrame: Up to 52.6 months
measure: Common in all parts: time to Progerssion (TTP)
timeFrame: Up to 52.6 months
measure: Common in all parts: Percentage of patients who switch to transplant
timeFrame: Up to 52.6 months
measure: Safety (Phase 2) - number of subjects with AEs, abnormal clinical laboratory values or physical exam results.
timeFrame: Up to 52.6 months
measure: Exploratory (Phase 1 dose-escalation part) - Assessment changes in cIAP in PBMC.
timeFrame: Up to 52.6 months
Other outcomes:
Locations:
city: Yamagata
country: Japan
facility: Yamagata University Hospital
Study officials:
affiliation: Otsuka Pharmaceutical Co., Ltd.
name: Nobuhito Sanada
role: STUDY_DIRECTOR
References: