Clinical Trials /

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

NCT04362007

Description:

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.

Related Conditions:
  • T-Cell Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: 401-102-00001
  • NCT ID: NCT04362007

Conditions

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

Interventions

DrugSynonymsArms
ASTX660Phase 1 dose-escalation part
ASTX660Phase 1 ATLL expansion part
ASTX660Phase 2

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Phase 1 dose-escalation partExperimentalSubjects 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.
  • ASTX660
Phase 1 ATLL expansion partExperimentalSubjects 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.
  • ASTX660
Phase 2ExperimentalSubjects 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.
  • ASTX660

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety (Phase 1 dose-escalation part) - number of subjects with dose-limiting toxicities (DLTs), AEs, abnormal clinical laboratory values or physical exam results
Time Frame:Up to 25 months
Safety Issue:
Description:Incidence of DLTs and other adverse events (AEs)

Secondary Outcome Measures

Measure:Pharmacokinetic outcome of concentration-time curve (AUC)
Time Frame:Up to 52 months
Safety Issue:
Description:Assessment of pharmacokinetic parameter area under the concentration-time curve (AUC).
Measure:Pharmacokinetic outcome of maximum concentration (Cmax)
Time Frame:Up to 52 months
Safety Issue:
Description:Assessment of pharmacokinetic parameter maximum concentration (Cmax).
Measure:Pharmacokinetic outcome of time to maximum concentration (Tmax)
Time Frame:Up to 52 months
Safety Issue:
Description:Assessment of pharmacokinetic parameter time to maximum concentration (Tmax).
Measure:Pharmacokinetic outcome of samples over time
Time Frame:Up to 52 months
Safety Issue:
Description:Assessment of pharmacokinetic parameter elimination half life (t½).
Measure:Pharmacokinetic outcome of clearance of drug from plasma
Time Frame:Up to 52 months
Safety Issue:
Description:Assessment of pharmacokinetic parameter clearance of drug from plasma.
Measure:Common in all parts: antitumor activity assessed by ORR
Time Frame:Up to 52 months
Safety Issue:
Description:Antitumor activity by Investigator- or subinvestigator-assessed ORR
Measure:Common in all parts: antitumor activity assessed by duration of response (DOR)
Time Frame:Up to 52 months
Safety Issue:
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.
Measure:Common in all parts: antitumor activity assessed by progression free survival (PFS)
Time Frame:Up to 52 months
Safety Issue:
Description:Number of days from the start of the study treatment to disease progression or death, whichever occurs first.
Measure:Common in all parts: overall survival (OS)
Time Frame:Up to 52 months
Safety Issue:
Description:Number of days from the day the subject received the first study treatment to the date of death, regardless of cause.
Measure:Common in all parts: time to response (TTR)
Time Frame:Up to 52 months
Safety Issue:
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.
Measure:Common in all parts: time to Progerssion (TTP)
Time Frame:Up to 52 months
Safety Issue:
Description:Time from the day the subject received the first study treatment to the date of relapse.
Measure:Common in all parts: Percentage of patients who switch to transplant
Time Frame:Up to 52 months
Safety Issue:
Description:Percentage of patients who switch to transplant
Measure:Safety (Phase 2) - number of subjects with AEs, abnormal clinical laboratory values or physical exam results.
Time Frame:Up to 22 months
Safety Issue:
Description:Incidence of adverse events (AEs)
Measure:Exploratory (Phase 1 dose-escalation part) - Assessment changes in cIAP in PBMC.
Time Frame:Up to 22 months
Safety Issue:
Description:Percentage degradation of cIAP1 protein in PBMCs from baseline.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Otsuka Pharmaceutical Co., Ltd.

Last Updated

August 28, 2020