Clinical trial NCT03009344: A Study of Tazemetostat in Participants With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma
Official title: A Phase 1 Study of Tazemetostat in Patients With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma
Keywords: relapsed or refractory B-cell non-Hodgkin's lymphoma
tazemetostat
Japan
E7438
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2017-01-04
Enrollment: 7
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a multicenter, single-arm, open-label, Phase 1 study to assess the tolerability, safety, pharmacokinetics, and preliminary anti-tumor activity of tazemetostat in participants with relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL).


Eligibility criteria: Inclusion Criteria:

* Participants with histological diagnosis of B-cell non-Hodgkin's lymphoma
* Participant who has measurable disease
* Participant who had previous therapy with systemic chemotherapy and/or antibody therapy
* Participant who had progressive disease (PD) or did not have a response (complete response \[CR\] or partial response \[PR\]) in previous systemic therapy, or relapsed or progressed after previous systemic therapy
* Participant with Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
* Participant with life expectancy of ≥3 months from starting study drug administration
* Participant with adequate renal, bone marrow, and liver function
* Participant with left ventricular ejection fraction (LVEF) \> 50%
* Male and female participant ≥20 years of age at the time of informed consent
* Participant who has provided written consent to participate in the study

Exclusion Criteria:

* Participant with prior exposure to EZH2 inhibitor
* Participant with a history or a presence of central nerves invasion
* Participant with allogeneic stem cell transplantation
* Participant with medical need for the continued use of potent or moderate inhibitors of CYP3A or P-gp, or potent or moderate inducer of CYP3A (including St. John's wort).
* Participant with significant cardiovascular impairment
* Participant with prolongation of corrected QT interval using Fridericia's formula (QTcF) to \> 480 milliseconds (msec)
* Participant with venous thrombosis or pulmonary embolism within the last 3 months before starting study drug
* Participant with complications of hepatic cirrhosis, interstitial pneumonia, or pulmonary fibrosis
* Participant with active infection requiring systemic therapy
* Women of childbearing potential or man of impregnate potential who don't agree to use a medically effective method for contraception for periods from before informed consent to during the clinical study and 30 days later from last administration of study drug
* Woman who are pregnant or breastfeeding
* Participant who were deemed as inappropriate to participate in the study by the investigator or sub-investigator

Primary outcomes:
measure: Number of Participants With Dose-limiting Toxicities (DLTs)
timeFrame: Cycle 0 and Cycle 1 (Cycle 0=4 days, Cycle 1=28 days)
Secondary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: From the date of first dose up to 30 days after the last dose of study drug (up to 40 months)
measure: Cmax: Maximum Plasma Concentration of Tazemetostat and Its Metabolite ER-897387
timeFrame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)
measure: Tmax: Time to Reach Maximum Plasma Concentration (Cmax) of Tazemetostat and Its Metabolite ER-897387
timeFrame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)
measure: AUC(0-12 Hours): Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post-dose of Tazemetostat and Its Metabolite ER-897387
timeFrame: Cycle 0 Day 1: 0-12 hours post-dose (Cycle 0 length=4 days)
measure: AUC(0-t Hours): Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration of Tazemetostat and Its Metabolite ER-897387
timeFrame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)
measure: AUC(0-infinity): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity of Tazemetostat and Its Metabolite ER-897387
timeFrame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)
measure: Lambda z: Terminal Phase Elimination Rate Constant of Tazemetostat and Its Metabolite ER-897387
timeFrame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)
measure: T1/2: Terminal Half-life of Tazemetostat and Its Metabolite ER-897387
timeFrame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
measure: CL/F: Apparent Total Body Clearance of Tazemetostat
timeFrame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)
measure: Vz/F: Apparent Volume of Distribution at Terminal Phase of Tazemetostat
timeFrame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
measure: MRT: Mean Residence Time of Tazemetostat and Its Metabolite ER-897387
timeFrame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)
measure: AUC(0-tau): Area Under the Plasma Concentration-time Curve Over the Dosing Interval of Tazemetostat and Its Metabolite ER-897387
timeFrame: Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
measure: Css,Av: Average Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387
timeFrame: Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
measure: Css,Max: Maximum Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387
timeFrame: Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
measure: Css,Min: Minimum Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387
timeFrame: Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
measure: PTF: Peak-trough Fluctuation Ratio of Tazemetostat and Its Metabolite ER-897387
timeFrame: Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
measure: Tss,Max: Time to Reach the Maximum Plasma Concentration (Cmax) at Steady State of Tazemetostat and Its Metabolite ER-897387
timeFrame: Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
measure: CLss/F: Apparent Total Body Clearance of Tazemetostat at Steady State
timeFrame: Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
measure: Rac (Cmax): Accumulation Ratio of Cmax for Tazemetostat and Its Metabolite ER-897387
timeFrame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) and Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
measure: Rac (AUC): Accumulation Ratio of AUC for Tazemetostat and Its Metabolite ER-897387
timeFrame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) and Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
measure: Rss: Steady State Accumulation Ratio of Tazemetostat and Its Metabolite ER-897387
timeFrame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) and Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
measure: Ae: Amount of Unchanged Drug Tazemetostat Excreted in Urine
timeFrame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
measure: Fe: Fraction of Tazemetostat Dose Excreted in Urine
timeFrame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
measure: CLR: Renal Clearance of Tazemetostat
timeFrame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
measure: Percentage of Participants With Objective Response
timeFrame: From the date of first dose of study drug to the date of first documentation of disease progression or death, whichever occurred first (up to 39 months)
Other outcomes:
Locations:
city: Isehara
country: Japan
facility: Eisai Trial Site
state: Kanagawa
city: Chuo-ku
country: Japan
facility: Eisai Trial Site
state: Tokyo
Study officials:
References: