Clinical Trial: A Japanese Phase 1/2 Study to Assess the Efficacy, Safety and Pharmacokinetics of Romidepsin in Patients With Peripheral T-cell Lymphoma (PTCL)

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Japanese Phase 1/2, Multicenter, Open-label Study to Assess the Efficacy, Tolerability, Safety and Pharmacokinetics of Romidepsin in Subjects With the Progressive or Relapsed P

Brief Summary: The purpose of the study was to assess efficacy, tolerability, safety and pharmacokinetics of Romidepsin in subjects with progressive or relapsed peripheral T-cell lymphoma

Detailed Summary: This is a Phase 1/2, non-randomized, open-label, single-arm trial with two phases. The first phase is a 3 + 3 dose escalation phase to determine a recommended dose for treating patients with Peripheral T-Cell Lymphoma (PTCL) or Cutaneous T-Cell Lymphoma (CTCL) based on the assessment of Dose Limiting Toxicities (DLTs).The second phase will assess efficacy at the recommended dose by measuring objective response [Complete Response (CR), Unconfirmed Complete Response (CR(u)) or Partial Response (PR)] and determining best overall response of each patient. Phase 1 will enroll a maximum of 12 patients and Phase 2 will enroll up to approximately 40 patients
Sponsor: Celgene

Current Primary Outcome:

  • Number of Participants With Dose-limiting Toxicity (DLT) in Accordance With National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 as Determined by the Efficacy and Safety Evaluation Committee (ESEC) [ Time Frame: Up to Day 28; Cycle 1 ]
    DLT was defined as an adverse event (AE) occurring in Cycle 1 in Phase 1 and judged that the causal relationship to the investigational product could not be denied. The severity of all AEs was graded based upon the NCI CTCAE version 3.0. DLTs were defined as: • Grade 4 Hemoglobin <6.5 g/dL • Grade 4 Neutrophil <500/μL continuing for at least 5 days • Febrile neutropenia (Grade 4 neutropenia caused by fever and ≥ 38.5° C for more than 1 hour) • Grade 4 thrombocyte (< 25,000/μL), or thrombocytopenia with hemorrhage requiring platelet transfusion • Nausea, vomiting, or diarrhea at > grade 3 in spite of treatment • Grade 3 ALT (alanine aminotransferase) or AST (aspartate aminotransferase) values continued for 7 days. • Grade 4 ALT or AST • Grade 2 arrhythmia • Grade 4 non-hematological AEs • Other grade 3 non-hematological AEs except transient fatigue, anorexia, hyponatremia, and tumor lysis syndrome • Other AEs leading to discontinuation of administration
  • Percentage of PTCL Participants With an Overall Best Response in Accordance With a Modified International Workshop Response Criteria (IWC) 1999 in Phase 2 [ Time Frame: Tumor assessments performed every 2 months; median follow-up time was 100 days; up to the data cut-off of 28 July 2015 ]
    Objective disease response in PTCL was defined as patients with a complete response (CR), unconfirmed complete response

    Original Primary Outcome:

    • Incidence of dose-limiting toxicity in accordance with Common Terminology Criteria for Adverse Events [ Time Frame: 1 month ]
    • Objective response rate (ORR) in accordance with International Workshop Response Criteria. [ Time Frame: 6 months ]


    Current Secondary Outcome:

    • Participants With Treatment-Emergent Adverse Events (TEAEs) Associated With Romidepsin [ Time Frame: Day 1 of study drug through 30 days after the last dose of study drug or discontinuation date; Up to data cut-off of 28 July 2015; maximum follow up time was 184.3 weeks ]
      An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. An AE that resulted in any of the outcomes was defined as a serious (SAE): • Death • Life-threatening event • An inpatient hospitalization or prolongation of existing hospitalization • Persistent or significant disability or incapacity; • Congenital anomaly or birth defect • Other important medical event The investigator judged the relationship of an AE to study drug based on the timing of the AE relative to drug administration and whether or not other drugs, therapeutic interventions, or underlying conditions could provide an explanation for the event. The severity of an AE was evaluated by the investigator according to Common Terminology Criteria for Adverse Events (CTCAE Version 3.0), Japanese Clinical Oncology Group (JCOG) where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death.
    • Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Romidepsin in Phase 1 [ Time Frame: Day 1 at Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration ]
      Area under the plasma concentration-time curve from time zero to the last quantifiable time point, calculated by the linear trapezoidal rule when concentrations are increasing and the logarithmic trapezoidal method when concentrations are decreasing.
    • Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC∞) of Romidepsin in Phase 1 [ Time Frame: Day 1 at Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration ]
      Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC∞) of romidepsin on Day 1; if possible the area under the concentration-time curve from time zero to infinity, calculated by the linear trapezoidal rule and extrapolated to infinity was calculated according to the following equation: AUC∞ = AUCt + (Ct/ λz ), where Ct is the last quantifiable concentration.
    • Maximum Plasma Concentration (Cmax) of Romidepsin in Phase 1 [ Time Frame: Day 1 at Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration ]
      The maximum observed plasma concentration of romidepsin (Cmax) obtained directly from the observed concentration versus time data
    • Time to Maximum Plasma Concentration of Romidepsin (Tmax) in Phase 1 [ Time Frame: Day 1 at Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration ]
      The time to first maximum observed plasma concentration of romidepsin after a single dose on Day 1.
    • Terminal Phase Half-life of Romidepsin (t½) in Phase 1 [ Time Frame: Day 1 at Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration. ]
      The terminal phase half-life of romidepsin after a single dose on Day 1, calculated according to the following equation: t½ = 0.693/λz, where λz is the terminal phase rate constant.
    • Apparent Total Clearance of Romidepsin (CL/F) of Romidepsin in Phase 1 [ Time Frame: Day 1 at Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration. ]
      The apparent total clearance of romidepsin after a single dose on Day 1, calculated as dose/AUC0-infinity.
    • Apparent Volume of Distribution (Vz/F) of Romidepsin in Phase 1 [ Time Frame: Day 1 at Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration ]
      Apparent volume of distribution, was calculated according to the equation: Vd/F = (CL/F)/λz
    • AUC0-t, at Steady State (ss) of Romidepsin in Phase 1 at Cycle 1, Day 15 [ Time Frame: Day 15 at Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the s

      Original Secondary Outcome:

      • Maximum plasma concentration [ Time Frame: 1 month ]
      • Maximum plasma concentration time [ Time Frame: 1 month ]
      • Terminal elimination half-life [ Time Frame: 1 month ]
      • Area under the plasma concentration-time curve [ Time Frame: 1 month ]
      • Systemic clearance [ Time Frame: 1 month ]
      • Safety (the number of participants with adverse events, incidence, severity, causality) [ Time Frame: 6 months ]
      • Cardiac function monitoring by use of electrocardiogram [ Time Frame: 6 months ]
      • Objective response rate [ Time Frame: 6 months ]
      • Time to Response [ Time Frame: 6 months ]
      • Duration of Response [ Time Frame: 6 months ]
      • Time to Progression [ Time Frame: 6 months ]


      Information By: Celgene

      Dates:
      Date Received: October 18, 2011
      Date Started: December 2011
      Date Completion: June 2018
      Last Updated: February 1, 2017
      Last Verified: February 2017