A Study of Tazemetostat in Participants With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma

April 6, 2022 updated by: Eisai Co., Ltd.

A Phase 1 Study of Tazemetostat in Patients With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

7

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
    • Kanagawa
      • Isehara, Kanagawa, Japan
        • Eisai Trial Site
    • Tokyo
      • Chuo-ku, Tokyo, Japan
        • Eisai Trial Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Tazemetostat 800 mg
Participants will receive oral tazemetostat at a starting dose of 800 milligrams (mg) as a single dose (Cycle 0) and 800 mg twice a day as continuous dosing (Cycle 1 and later) (Cycle 0 duration=4 days) (Cycle 1 and later duration= 28 days).
Drug: Tazemetostat
Tazemetostat tablets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Dose-limiting Toxicities (DLTs)
Time Frame: Cycle 0 and Cycle 1 (Cycle 0=4 days, Cycle 1=28 days)
DLTs as per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) were defined as: 1) Grade 4 neutropenia for greater than (>) 7 days; 2) greater than or equal to (>=) Grade 3 febrile neutropenia; 3) Grade 4 thrombocytopenia and Grade 3 thrombocytopenia with bleeding; 4) Grade 4 anemia or anemia requiring erythrocyte transfusion; 5) >=Grade 3 nausea, vomiting, or diarrhea that persisted >7 days despite maximal medical therapy; 6) >=Grade 3 non-hematological laboratory abnormalities with clinical symptoms that persisted >7 days; 7) Other Grade 3 toxicity lasting >7 days or Grade 4 non-hematological toxicity of any duration; 8) Failure to administer >=75 percent (%) of the planned administration number of study drug in Cycle 1 as a result of treatment-related toxicity. Here, number of participants who had DLT were reported.
Cycle 0 and Cycle 1 (Cycle 0=4 days, Cycle 1=28 days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame: From the date of first dose up to 30 days after the last dose of study drug (up to 40 months)
TEAE was defined as an adverse event (AE) that emerged during time from first dose to 30 days following last dose of drug, having been absent at pretreatment or reemerged during treatment, having been present at pretreatment but stopped before treatment, or worsened in severity during treatment relative to pretreatment state, when AE was continuous. Number of participants with TEAEs were reported based on their safety assessments of laboratory tests, physical examination, regular measurement of vital signs, body weight, echocardiograms/multigated acquisition (MUGA) scans to assess left ventricular ejection fraction, eastern cooperative oncology group-performance status (ECOG-PS) and electrocardiograms parameter values. SAE was defined as untoward medical occurrence that at any dose resulted in death; was life threatening; resulted in persistent or significant disability; was congenital anomaly or medically important due to other reasons than above mentioned criteria.
From the date of first dose up to 30 days after the last dose of study drug (up to 40 months)
Cmax: Maximum Plasma Concentration of Tazemetostat and Its Metabolite ER-897387
Time Frame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)
Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)
Tmax: Time to Reach Maximum Plasma Concentration (Cmax) of Tazemetostat and Its Metabolite ER-897387
Time Frame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)
Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)
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
Time Frame: Cycle 0 Day 1: 0-12 hours post-dose (Cycle 0 length=4 days)
Cycle 0 Day 1: 0-12 hours post-dose (Cycle 0 length=4 days)
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
Time Frame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)
Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)
AUC(0-infinity): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity of Tazemetostat and Its Metabolite ER-897387
Time Frame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)
Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)
Lambda z: Terminal Phase Elimination Rate Constant of Tazemetostat and Its Metabolite ER-897387
Time Frame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)
Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.
Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)
T1/2: Terminal Half-life of Tazemetostat and Its Metabolite ER-897387
Time Frame: 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)
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)
CL/F: Apparent Total Body Clearance of Tazemetostat
Time Frame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)
Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)
Vz/F: Apparent Volume of Distribution at Terminal Phase of Tazemetostat
Time Frame: 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)
Vz/F for Cycle 0 Day 1 was calculated as Dose divided by ([lambda z]*[AUC0-infinity]) and for Cycle 1 Day 15 was calculated as Dose divided by ([lambda z]*[AUC0-tau]).
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)
MRT: Mean Residence Time of Tazemetostat and Its Metabolite ER-897387
Time Frame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)
MRT of tazemetostat and its metabolite ER-897387 was calculated as MRT=AUMC(0-infinity)/AUC(0-infinity), where AUMC(0-infinity) was the area under the first moment curve extrapolated to infinity and AUC(0-infinity) was area under the concentration-time curve from zero time extrapolated to infinite time.
Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)
AUC(0-tau): Area Under the Plasma Concentration-time Curve Over the Dosing Interval of Tazemetostat and Its Metabolite ER-897387
Time Frame: Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
Css,Av: Average Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387
Time Frame: Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
Css,Max: Maximum Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387
Time Frame: Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
Css,Min: Minimum Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387
Time Frame: Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
PTF: Peak-trough Fluctuation Ratio of Tazemetostat and Its Metabolite ER-897387
Time Frame: Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
The PTF within complete dosing interval at steady state, calculated as PTF (%) = ([Cmax - Cmin]/Cav) multiplied by 100. Here, Cmin means the minimum plasma concentration, Cmax means the maximum plasma concentration and Cav means the average plasma concentration of drug and metabolite.
Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
Tss,Max: Time to Reach the Maximum Plasma Concentration (Cmax) at Steady State of Tazemetostat and Its Metabolite ER-897387
Time Frame: Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
CLss/F: Apparent Total Body Clearance of Tazemetostat at Steady State
Time Frame: Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
Rac (Cmax): Accumulation Ratio of Cmax for Tazemetostat and Its Metabolite ER-897387
Time Frame: 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)
Rac (Cmax) was calculated as the ratio of maximum observed concentration at steady state (Css,max) on Cycle 1 Day 15 divided by Cmax on Cycle 0 Day 1.
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)
Rac (AUC): Accumulation Ratio of AUC for Tazemetostat and Its Metabolite ER-897387
Time Frame: 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)
Rac (AUC) was calculated as the ratio of AUC(0-tau) on Cycle 1 Day 15 divided by AUC(0-12 hours) on Cycle 0 Day 1.
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)
Rss: Steady State Accumulation Ratio of Tazemetostat and Its Metabolite ER-897387
Time Frame: 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)
Rss was calculated as the ratio of AUC(0-tau) on Cycle 1 Day 15 divided by AUC(0-infinity) on Cycle 0 Day 1.
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)
Ae: Amount of Unchanged Drug Tazemetostat Excreted in Urine
Time Frame: 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)
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)
Fe: Fraction of Tazemetostat Dose Excreted in Urine
Time Frame: 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)
The fraction of dose excreted in urine was calculated as: Cumulative amount of unchanged drug excreted in urine (Ae)/Dose*100.
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)
CLR: Renal Clearance of Tazemetostat
Time Frame: 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)
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)
Percentage of Participants With Objective Response
Time Frame: 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)
Objective response was assessed by investigator based on the Lugano Classification (CT-Based) response criteria. Objective response rate was defined as the percentage of participants who had a Best Overall Response (BOR) of complete response (CR) or partial response (PR). CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to less than (<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Eisai Co., Ltd.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 10, 2017

Primary Completion (Actual)

July 12, 2017

Study Completion (Actual)

June 17, 2020

Study Registration Dates

First Submitted

December 30, 2016

First Submitted That Met QC Criteria

December 30, 2016

First Posted (Estimate)

January 4, 2017

Study Record Updates

Last Update Posted (Actual)

November 10, 2022

Last Update Submitted That Met QC Criteria

April 6, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • E7438-J081-106

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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