Relapsed or Refractory Peripheral T-cell Lymphoma(PTCL),Cutaneous T-cell Lymphoma(CTCL),Adult T-cell Leukemia/Lymphoma(ATLL)
Conditions
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.
Interventions
DRUGASTX660
Treatment of ASTX660 for r/r PTCL and r/r CTCL
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety (Phase 1 Dose-escalation Part) - Number of Subjects With Dose-limiting Toxicities (DLTs), AEs, Abnormal Clinical Laboratory Values or Physical Exam Results | 28 days (Day1 to Day29) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Assessment of pharmacokinetic parameter area under the concentration-time curve (AUC). |
| 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 | Assessment of pharmacokinetic parameter maximum concentration (Cmax). |
| 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 | Assessment of pharmacokinetic parameter time to maximum concentration (Tmax). |
| 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 | Assessment of pharmacokinetic parameter elimination half life (t½). |
| 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 | Assessment of pharmacokinetic parameter clearance of drug from plasma. |
Countries
Japan
Contacts
STUDY_DIRECTORNobuhito Sanada
Otsuka Pharmaceutical Co., Ltd.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 77 years STANDARD_DEVIATION 0 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment Japan | 1 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 1 |
| other Total, other adverse events | 7 / 7 | 1 / 1 |
| serious Total, serious adverse events | 0 / 7 | 0 / 1 |
Outcome results
None listed