Study of Tazemetostat in Participants With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma With EZH2 Gene Mutation

Sponsor
Eisai Co., Ltd. (Industry)
Overall Status
Completed
CT.gov ID
NCT03456726
Collaborator
(none)
20
28
2
44.3
0.7
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Study Details

Study Description

Brief Summary

This is a multicenter, open-label, Phase 2 study to assess the efficacy and safety of tazemetostat in participants with relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL) with EZH2 gene mutation.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
20 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2 Study of Tazemetostat in Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma With EZH2 Gene Mutation
Actual Study Start Date :
Apr 9, 2018
Actual Primary Completion Date :
Dec 17, 2021
Actual Study Completion Date :
Dec 17, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: FL with EZH2 gene mutation

Participants with follicular lymphoma (FL) with the EZH2 gene mutation will receive oral tazemetostat at a starting dose of 800 milligrams (mg) twice daily (1600 mg total daily dose) by continuous regimen, no less than 8 hours between doses.

Drug: Tazemetostat
Tazemetostat will be provided as a 200 mg oral tablet.

Experimental: DLBCL with EZH2 gene mutation

Participants with diffuse large B-cell lymphoma (DLBCL) with the EZH2 gene mutation will receive oral tazemetostat at a starting dose of 800 mg twice daily (1600 mg total daily dose) by continuous regimen, no less than 8 hours between doses.

Drug: Tazemetostat
Tazemetostat will be provided as a 200 mg oral tablet.

Outcome Measures

Primary Outcome Measures

  1. Objective response rate (ORR) [From administration of the first dose of the study drug until disease progression, development of unacceptable toxicity, participant requests to discontinue, withdrawal of consent, or study termination (up to 30 months)]

    ORR is defined as the number of participants with a best overall response of complete response or partial response.

Secondary Outcome Measures

  1. Progression-free survival (PFS) [From administration of the first dose of the study drug to the date of the first event (disease progression, death, etc.) (up to 30 months)]

  2. Duration of response (DOR) [From confirmation of the first response to the date of the first event (disease progression, death, etc.) (up to 30 months)]

  3. Time to response (TTR) [From administration of the first dose of the study drug to confirmation of the first response (up to 30 months)]

  4. Number of participants with any adverse event, as an assessment of safety [From administration of the first dose of the study drug to 30 days after the last dose (up to 30 months)]

Eligibility Criteria

Criteria

Ages Eligible for Study:
20 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Participants with histological diagnosis of B-cell non-Hodgkin's lymphoma (NHL) as follows:

  • Cohort 1: Follicular lymphoma (FL)

  • Cohort 2: Diffuse large B-cell lymphoma (including primary mediastinal B-cell lymphoma and transformed FL)

  • Participants who have confirmed EZH2 gene mutation of tumor in central laboratory

  • Participants who have measurable disease

  • Participants who had previous therapy with systemic chemotherapy and/or antibody therapy and for which no standard therapy exists

  • Participants who had progressive disease or did not have response (complete response or partial response) in previous systemic therapy, or relapsed or progressed after previous systemic therapy

  • Participants with Eastern Cooperative Oncology Group performance status of 0 to 1

  • Participants with life expectancy of ≥3 months from starting study drug administration

  • Participants with adequate renal, liver, and bone marrow function

  • Male and female participants ≥20 years of age at the time of informed consent

  • Participants who has provided written consent to participate in the study

Exclusion Criteria:
  • Participants with prior exposure to EZH2 inhibitor

  • Participants with a history or a presence of central nerves invasion

  • Participants with malignant pleural effusion, cardiac effusion, or ascites retention

  • Participants with allogeneic stem cell transplantation

  • Participants with medical need for the continued use of potent inhibitors of Cytochrome P450 3A (CYP3A)or potent inducer of CYP3A (including St. John's wort)

  • Participants with significant cardiovascular impairment

· Participants with prolongation of corrected QT interval using Fridericia's formula to > 480 milliseconds (msec)

  • Participants with venous thrombosis or pulmonary embolism within the last 3 months before starting study drug

  • Participants with complications of hepatic cirrhosis, interstitial pneumonia or pulmonary fibrosis

  • Participants with active infection requiring systemic therapy

  • Women of childbearing potential or man of impregnate potential who don't agree that both the participant and his/her partner will use a medically effective method for contraception for periods from before informed consent to during the clinical study and 30 days later (for males 90 days later) from last administration of study drug

  • Woman who are pregnant or breastfeeding

  • Participants who were deemed as inappropriate to participate in the study by the investigator or sub-investigator

  • Have any prior history of T-cell lymphoblastic lymphoma/T-cell acute lymphoblastic leukemia or myeloid malignancies, including myelodysplastic syndrome

Contacts and Locations

Locations

Site City State Country Postal Code
1 1004 Eisai Trial Site Nagoya Aichi Japan
2 1029 Eisai Trial Site Nagoya Aichi Japan
3 1020 Eisai Trial Site Ota Gunma Japan
4 1007 Eisai Trial Site Sapporo Hokkaido Japan
5 1019 Eisai Trial Site Kobe Hyogo Japan
6 1005 Eisai Trial Site Tsukuba Ibaraki Japan
7 1002 Eisai Trial Site Isehara Kanagawa Japan
8 1028 Eisai Trial Site Yokohama Kanagawa Japan
9 1021 Eisai Trial Site Sendai Miyagi Japan
10 1013 Eisai Trial Site Osakasayama Osaka Japan
11 1006 Eisai Trial Site Suita Osaka Japan
12 1027 Eisai Trial Site Suntou-gun Shizuoka Japan
13 1026 Eisai Trial Site Bunkyo-ku Tokyo Japan
14 1001 Eisai Trial Site Chuo-ku Tokyo Japan
15 1025 Eisai Trial Site Koto-ku Tokyo Japan
16 1017 Eisai Trial Site Minato-ku Tokyo Japan
17 1022 Eisai Trial Site Aomori Japan
18 1010 Eisai Trial Site Chiba Japan
19 1012 Eisai Trial Site Fukuoka Japan
20 1016 Eisai Trial Site Fukuoka Japan
21 1011 Eisai Trial Site Hiroshima Japan
22 1024 Eisai Trial Site Kumamoto Japan
23 1003 Eisai Trial Site Kyoto Japan
24 1008 Eisai Trial Site Kyoto Japan
25 1023 Eisai Trial Site Nagasaki Japan
26 1009 Eisai Trial Site Okayama Japan
27 1015 Eisai Trial Site Osaka Japan
28 1018 Eisai Trial Site Yamagata Japan

Sponsors and Collaborators

  • Eisai Co., Ltd.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Eisai Co., Ltd.
ClinicalTrials.gov Identifier:
NCT03456726
Other Study ID Numbers:
  • E7438-J081-206
First Posted:
Mar 7, 2018
Last Update Posted:
Jan 14, 2022
Last Verified:
May 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
Yes
Keywords provided by Eisai Co., Ltd.
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jan 14, 2022