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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04362007
Recruitment Status : Recruiting
First Posted : April 24, 2020
Last Update Posted : August 31, 2020
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Co., Ltd.

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.


Condition or disease Intervention/treatment Phase
Relapsed or Refractory Peripheral T-cell Lymphoma(PTCL),Cutaneous T-cell Lymphoma(CTCL),Adult T-cell Leukemia/Lymphoma(ATLL) Drug: ASTX660 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 61 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 14, 2020
Estimated Primary Completion Date : September 2024
Estimated Study Completion Date : September 2024


Arm Intervention/treatment
Experimental: Phase 1 dose-escalation part
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
Treatment of ASTX660 for r/r PTCL and r/r CTCL

Experimental: Phase 1 ATLL expansion part
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
Treatment of ASTX660 for r/r ATLL

Experimental: Phase 2
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
Treatment of ASTX660 for r/r PTCL




Primary Outcome Measures :
  1. 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 ]
    Incidence of DLTs and other adverse events (AEs)

  2. Safety (Phase 1 ATLL expansion part) - number of subjects with AEs, abnormal clinical laboratory values or physical exam results [ Time Frame: Up to 52 months ]
    Incidence of adverse events (AEs)

  3. Efficacy (Phase 2) - antitumor activity assessed by objective response rate (ORR) [ Time Frame: Up to 22 months ]
    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 :
  1. Pharmacokinetic outcome of concentration-time curve (AUC) [ Time Frame: Up to 52 months ]
    Assessment of pharmacokinetic parameter area under the concentration-time curve (AUC).

  2. Pharmacokinetic outcome of maximum concentration (Cmax) [ Time Frame: Up to 52 months ]
    Assessment of pharmacokinetic parameter maximum concentration (Cmax).

  3. Pharmacokinetic outcome of time to maximum concentration (Tmax) [ Time Frame: Up to 52 months ]
    Assessment of pharmacokinetic parameter time to maximum concentration (Tmax).

  4. Pharmacokinetic outcome of samples over time [ Time Frame: Up to 52 months ]
    Assessment of pharmacokinetic parameter elimination half life (t½).

  5. Pharmacokinetic outcome of clearance of drug from plasma [ Time Frame: Up to 52 months ]
    Assessment of pharmacokinetic parameter clearance of drug from plasma.

  6. Common in all parts: antitumor activity assessed by ORR [ Time Frame: Up to 52 months ]
    Antitumor activity by Investigator- or subinvestigator-assessed ORR

  7. Common in all parts: antitumor activity assessed by duration of response (DOR) [ Time Frame: Up to 52 months ]
    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.

  8. Common in all parts: antitumor activity assessed by progression free survival (PFS) [ Time Frame: Up to 52 months ]
    Number of days from the start of the study treatment to disease progression or death, whichever occurs first.

  9. Common in all parts: overall survival (OS) [ Time Frame: Up to 52 months ]
    Number of days from the day the subject received the first study treatment to the date of death, regardless of cause.

  10. Common in all parts: time to response (TTR) [ Time Frame: Up to 52 months ]
    Time from the day the subject received the first study treatment to the date of the earliest assessment of complete response or partial response.

  11. Common in all parts: time to Progerssion (TTP) [ Time Frame: Up to 52 months ]
    Time from the day the subject received the first study treatment to the date of relapse.

  12. Common in all parts: Percentage of patients who switch to transplant [ Time Frame: Up to 52 months ]
    Percentage of patients who switch to transplant

  13. Safety (Phase 2) - number of subjects with AEs, abnormal clinical laboratory values or physical exam results. [ Time Frame: Up to 22 months ]
    Incidence of adverse events (AEs)

  14. Exploratory (Phase 1 dose-escalation part) - Assessment changes in cIAP in PBMC. [ Time Frame: Up to 22 months ]
    Percentage degradation of cIAP1 protein in PBMCs from baseline.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04362007


Contacts
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Contact: Drug Information Center +81-3-6361-7314

Locations
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Japan
Yamagata University Hospital Recruiting
Yamagata, Japan
Sponsors and Collaborators
Otsuka Pharmaceutical Co., Ltd.
Investigators
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Study Director: Junji Ikeda Otsuka Pharmaceutical Co., Ltd.
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Responsible Party: Otsuka Pharmaceutical Co., Ltd.
ClinicalTrials.gov Identifier: NCT04362007    
Other Study ID Numbers: 401-102-00001
First Posted: April 24, 2020    Key Record Dates
Last Update Posted: August 31, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, T-Cell
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Lymphoma, T-Cell, Peripheral
Lymphoma, T-Cell, Cutaneous
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia