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

NCT03456726 | Completed Phase 2 Results FDA Drug

• 1 other identifier: E7438-J081-206
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 28

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.

Conditions

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

Keywords

EZH2 gene mutation; Tazemetostat; Diffuse large B-cell lymphoma; Follicular lymphoma

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR) Based on Independent Reviewer Assessment

  ORR was defined as percentage of participants with confirmed best overall response (BOR) of complete response (CR) or partial response (PR) using independent reviewer assessment based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. BOR of CR and PR was confirmed by a subsequent CR assessment and CR or PR assessment. CR: disappearance of all measurable, non-measurable lesions and no unequivocal new lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to less than (\<) 10 millimeter (mm). PR: at least a 30 percent (%) decrease in sum of diameters (SOD) of target lesions, taking as reference the baseline SOD and there are no unequivocal new lesions, and no progression of non-target disease. The 2-sided 95% confidence interval (CI) was calculated by Clopper-Pearson method.

  From date of first dose of study drug administration to date of PD or death, whichever occurred first (up to 3 years 4 months)

• ORR Based on Investigator Assessment

  ORR was defined as percentage of participants with confirmed BOR of CR or PR using investigator assessment based on RECIST 1.1. BOR of CR and PR was confirmed by a subsequent CR assessment and CR or PR assessment. CR: disappearance of all measurable, non-measurable lesions and no unequivocal new lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis \<10 mm. PR: at least a 30% decrease in SOD of target lesions, taking as reference the baseline SOD and there are no unequivocal new lesions, and no progression of non-target disease. The 2-sided 95% CI was calculated by Clopper-Pearson method.

  From date of first dose of study drug administration to date of PD or death, whichever occurred first (up to 3 years 4 months)

Secondary Outcomes (7)

• Progression-free Survival (PFS) Based on Independent Reviewer Assessment

  From date of first dose of study drug administration to date of PD or death, whichever occurred first (up to 3 years 4 months)

• PFS Based on Investigator Assessment

  From date of first dose of study drug administration to date of PD or death, whichever occurred first (up to 3 years 4 months)

• Duration of Response (DOR) Based on Independent Reviewer Assessment

  From the date of first confirmed objective response (OR) to PD or death due to confirmed PR or CR (up to 3 years 4 months)

• DOR Based on Investigator Assessment

  From the date of first confirmed OR to PD or death due to any cause for those participants with a confirmed PR or CR (up to 3 years 4 months)

• Time to Response (TTR) Based on Independent Reviewer Assessment

  From the date of first dose until date of first observation of CR or PR (up to 3 years 4 months)

Study Arms (2)

FL with EZH2 gene mutation

EXPERIMENTAL

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

DLBCL with EZH2 gene mutation

EXPERIMENTAL

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

Interventions

Tazemetostat DRUG

Tazemetostat will be provided as a 200 mg oral tablet.

DLBCL with EZH2 gene mutation; FL with EZH2 gene mutation

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 (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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eisai Co., Ltd.: lead

Study Sites (28)

1004 Eisai Trial Site

Nagoya, Aichi-ken, Japan

Location

1029 Eisai Trial Site

Nagoya, Aichi-ken, Japan

Location

1020 Eisai Trial Site

Ōta, Gunma, Japan

Location

1007 Eisai Trial Site

Sapporo, Hokkaido, Japan

Location

1019 Eisai Trial Site

Kobe, Hyōgo, Japan

Location

1005 Eisai Trial Site

Tsukuba, Ibaraki, Japan

Location

1002 Eisai Trial Site

Isehara, Kanagawa, Japan

Location

1028 Eisai Trial Site

Yokohama, Kanagawa, Japan

Location

1021 Eisai Trial Site

Sendai, Miyagi, Japan

Location

1013 Eisai Trial Site

Sayama, Osaka, Japan

Location

1006 Eisai Trial Site

Suita, Osaka, Japan

Location

1027 Eisai Trial Site

Suntou-gun, Shizuoka, Japan

Location

1026 Eisai Trial Site

Bunkyo-ku, Tokyo, Japan

Location

1001 Eisai Trial Site

Chuo-ku, Tokyo, Japan

Location

1025 Eisai Trial Site

Koto-ku, Tokyo, Japan

Location

1017 Eisai Trial Site

Minato-ku, Tokyo, Japan

Location

1022 Eisai Trial Site

Aomori, Japan

Location

1010 Eisai Trial Site

Chiba, Japan

Location

1012 Eisai Trial Site

Fukuoka, Japan

Location

1016 Eisai Trial Site

Fukuoka, Japan

Location

1011 Eisai Trial Site

Hiroshima, Japan

Location

1024 Eisai Trial Site

Kumamoto, Japan

Location

1003 Eisai Trial Site

Kyoto, Japan

Location

1008 Eisai Trial Site

Kyoto, Japan

Location

1023 Eisai Trial Site

Nagasaki, Japan

Location

1009 Eisai Trial Site

Okayama, Japan

Location

1015 Eisai Trial Site

Osaka, Japan

Location

1018 Eisai Trial Site

Yamagata, Japan

Location

Related Publications (1)

• Izutsu K, Ando K, Nishikori M, Shibayama H, Goto H, Kuroda J, Kato K, Imaizumi Y, Nosaka K, Sakai R, Abe M, Hojo S, Nakanishi T, Rai S. Tazemetostat for relapsed/refractory B-cell non-Hodgkin lymphoma with EZH2 mutation in Japan: 3-year follow-up for a phase II study. Int J Hematol. 2024 Nov;120(5):621-630. doi: 10.1007/s12185-024-03834-9. Epub 2024 Aug 23.

  PMID: 39179948 DERIVED

MeSH Terms

Conditions

Recurrence; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular

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

eisai-chiken_hotline@hhc.eisai.co.jp

None

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2018
• First Posted: March 7, 2018
• Study Start: April 9, 2018
• Primary Completion: December 17, 2021
• Study Completion: December 17, 2021
• Last Updated: December 16, 2022
• Results First Posted: December 16, 2022

Record last verified: 2021-04

Locations

JP (28)