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

NCT03009344 | Completed Phase 1 Results

• 1 other identifier: E7438-J081-106
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 2

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).

Conditions

Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma

Keywords

relapsed or refractory B-cell non-Hodgkin's lymphoma; tazemetostat; Japan; E7438

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Dose-limiting Toxicities (DLTs)

  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 Outcomes (25)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  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

  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

  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

  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

  Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)

Study Arms (1)

Tazemetostat 800 mg

EXPERIMENTAL

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

Interventions

Tazemetostat DRUG

Tazemetostat tablets.

Tazemetostat 800 mg

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eisai Co., Ltd.: lead

Study Sites (2)

Eisai Trial Site

Isehara, Kanagawa, Japan

Location

Eisai Trial Site

Chuo-ku, Tokyo, Japan

Location

MeSH Terms

Conditions

Recurrence; Lymphoma, B-Cell

Interventions

tazemetostat

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Inquiry Service
• Organization: Eisai Co., Ltd.

eisai-chiken_hotline@hhc.eisai.co.jp

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 30, 2016
• First Posted: January 4, 2017
• Study Start: January 10, 2017
• Primary Completion: July 12, 2017
• Study Completion: June 17, 2020
• Last Updated: November 10, 2022
• Results First Posted: November 10, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

JP (2)