Back to resultsA Phase I/II Study of ASTX660 in Patients With Relapsed or Refractory T-cell Lymphoma
Primary Purpose
Relapsed or Refractory Peripheral T-cell Lymphoma(PTCL),Cutaneous T-cell Lymphoma(CTCL),Adult T-cell Leukemia/Lymphoma(ATLL)
Status
Active
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
ASTX660
ASTX660
ASTX660
Sponsored by
About this trial
This is an interventional treatment trial for Relapsed or Refractory Peripheral T-cell Lymphoma(PTCL),Cutaneous T-cell Lymphoma(CTCL),Adult T-cell Leukemia/Lymphoma(ATLL)
Eligibility Criteria
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
Sites / Locations
- Yamagata University Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Phase 1 dose-escalation part
Phase 1 ATLL expansion part
Phase 2
Arm Description
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.
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.
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.
Outcomes
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
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
Incidence of adverse events (AEs)
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)
Secondary Outcome Measures
Pharmacokinetic outcome of concentration-time curve (AUC)
Assessment of pharmacokinetic parameter area under the concentration-time curve (AUC).
Pharmacokinetic outcome of maximum concentration (Cmax)
Assessment of pharmacokinetic parameter maximum concentration (Cmax).
Pharmacokinetic outcome of time to maximum concentration (Tmax)
Assessment of pharmacokinetic parameter time to maximum concentration (Tmax).
Pharmacokinetic outcome of samples over time
Assessment of pharmacokinetic parameter elimination half life (t½).
Pharmacokinetic outcome of clearance of drug from plasma
Assessment of pharmacokinetic parameter clearance of drug from plasma.
Common in all parts: antitumor activity assessed by ORR
Antitumor activity by Investigator- or subinvestigator-assessed ORR
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.
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.
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.
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.
Common in all parts: time to Progerssion (TTP)
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
Percentage of patients who switch to transplant
Safety (Phase 2) - number of subjects with AEs, abnormal clinical laboratory values or physical exam results.
Incidence of adverse events (AEs)
Exploratory (Phase 1 dose-escalation part) - Assessment changes in cIAP in PBMC.
Percentage degradation of cIAP1 protein in PBMCs from baseline.
Full Information
NCT ID
NCT04362007
First Posted
April 17, 2020
Last Updated
March 7, 2023
Sponsor
Otsuka Pharmaceutical Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT04362007
Brief Title
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
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 14, 2020 (Actual)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
September 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Otsuka Pharmaceutical Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed or Refractory Peripheral T-cell Lymphoma(PTCL),Cutaneous T-cell Lymphoma(CTCL),Adult T-cell Leukemia/Lymphoma(ATLL)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
61 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Phase 1 dose-escalation part
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 1 ATLL expansion part
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 2
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
ASTX660
Intervention Description
Treatment of ASTX660 for r/r PTCL and r/r CTCL
Intervention Type
Drug
Intervention Name(s)
ASTX660
Intervention Description
Treatment of ASTX660 for r/r ATLL
Intervention Type
Drug
Intervention Name(s)
ASTX660
Intervention Description
Treatment of ASTX660 for r/r PTCL
Primary Outcome Measure Information:
Title
Safety (Phase 1 dose-escalation part) - number of subjects with dose-limiting toxicities (DLTs), AEs, abnormal clinical laboratory values or physical exam results
Description
Incidence of DLTs and other adverse events (AEs)
Time Frame
Up to 25 months
Title
Safety (Phase 1 ATLL expansion part) - number of subjects with AEs, abnormal clinical laboratory values or physical exam results
Description
Incidence of adverse events (AEs)
Time Frame
Up to 52 months
Title
Efficacy (Phase 2) - antitumor activity assessed by objective response rate (ORR)
Description
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)
Time Frame
Up to 22 months
Secondary Outcome Measure Information:
Title
Pharmacokinetic outcome of concentration-time curve (AUC)
Description
Assessment of pharmacokinetic parameter area under the concentration-time curve (AUC).
Time Frame
Up to 52 months
Title
Pharmacokinetic outcome of maximum concentration (Cmax)
Description
Assessment of pharmacokinetic parameter maximum concentration (Cmax).
Time Frame
Up to 52 months
Title
Pharmacokinetic outcome of time to maximum concentration (Tmax)
Description
Assessment of pharmacokinetic parameter time to maximum concentration (Tmax).
Time Frame
Up to 52 months
Title
Pharmacokinetic outcome of samples over time
Description
Assessment of pharmacokinetic parameter elimination half life (t½).
Time Frame
Up to 52 months
Title
Pharmacokinetic outcome of clearance of drug from plasma
Description
Assessment of pharmacokinetic parameter clearance of drug from plasma.
Time Frame
Up to 52 months
Title
Common in all parts: antitumor activity assessed by ORR
Description
Antitumor activity by Investigator- or subinvestigator-assessed ORR
Time Frame
Up to 52 months
Title
Common in all parts: antitumor activity assessed by duration of response (DOR)
Description
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.
Time Frame
Up to 52 months
Title
Common in all parts: antitumor activity assessed by progression free survival (PFS)
Description
Number of days from the start of the study treatment to disease progression or death, whichever occurs first.
Time Frame
Up to 52 months
Title
Common in all parts: overall survival (OS)
Description
Number of days from the day the subject received the first study treatment to the date of death, regardless of cause.
Time Frame
Up to 52 months
Title
Common in all parts: time to response (TTR)
Description
Time from the day the subject received the first study treatment to the date of the earliest assessment of complete response or partial response.
Time Frame
Up to 52 months
Title
Common in all parts: time to Progerssion (TTP)
Description
Time from the day the subject received the first study treatment to the date of relapse.
Time Frame
Up to 52 months
Title
Common in all parts: Percentage of patients who switch to transplant
Description
Percentage of patients who switch to transplant
Time Frame
Up to 52 months
Title
Safety (Phase 2) - number of subjects with AEs, abnormal clinical laboratory values or physical exam results.
Description
Incidence of adverse events (AEs)
Time Frame
Up to 22 months
Title
Exploratory (Phase 1 dose-escalation part) - Assessment changes in cIAP in PBMC.
Description
Percentage degradation of cIAP1 protein in PBMCs from baseline.
Time Frame
Up to 22 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nobuhito Sanada
Organizational Affiliation
Otsuka Pharmaceutical Co., Ltd.
Official's Role
Study Director
Facility Information:
Facility Name
Yamagata University Hospital
City
Yamagata
Country
Japan
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
The focus of this study is a rare disease.
Learn more about this trial
A Phase I/II Study of ASTX660 in Patients With Relapsed or Refractory T-cell Lymphoma
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