Study of Tazemetostat in Participants With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma With EZH2 Gene Mutation
- Conditions
- Interventions
- Registration Number
- NCT03456726
- Lead Sponsor
- Eisai Co., Ltd.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 20
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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)
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Participants who have confirmed EZH2 gene mutation of tumor in central laboratory
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Participants who have measurable disease
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Participants who had previous therapy with systemic chemotherapy and/or antibody therapy and for which no standard therapy exists
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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
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Participants with Eastern Cooperative Oncology Group performance status of 0 to 1
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Participants with life expectancy of ≥3 months from starting study drug administration
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Participants with adequate renal, liver, and bone marrow function
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Male and female participants ≥20 years of age at the time of informed consent
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Participants who has provided written consent to participate in the study
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Participants with prior exposure to EZH2 inhibitor
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Participants with a history or a presence of central nerves invasion
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Participants with malignant pleural effusion, cardiac effusion, or ascites retention
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Participants with allogeneic stem cell transplantation
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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)
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Participants with significant cardiovascular impairment
· Participants with prolongation of corrected QT interval using Fridericia's formula to > 480 milliseconds (msec)
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Participants with venous thrombosis or pulmonary embolism within the last 3 months before starting study drug
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Participants with complications of hepatic cirrhosis, interstitial pneumonia or pulmonary fibrosis
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Participants with active infection requiring systemic therapy
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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
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Woman who are pregnant or breastfeeding
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Participants who were deemed as inappropriate to participate in the study by the investigator or sub-investigator
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Have any prior history of T-cell lymphoblastic lymphoma/T-cell acute lymphoblastic leukemia or myeloid malignancies, including myelodysplastic syndrome
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description FL with EZH2 gene mutation Tazemetostat 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. DLBCL with EZH2 gene mutation Tazemetostat 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.
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) 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) 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 mea...
ORR 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) 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) ha...
- Secondary Outcome Measures
Name Time Method 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 was assessed by independent reviewer assessment based on RECIST 1.1. PFS was defined as the time from the date of the first dose of study drug to the date of the first documentation of PD or death, whichever occurred first. PD for target lesion, a minimum 20% increase and a minimum 5 mm absolute increase in SOD compared to nadir, or PD for non-target les...
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) PFS was assessed by investigator assessment based on RECIST 1.1. PFS was defined as the time from the date of the first dose of study drug to the date of the first documentation of PD or death, whichever occurred first. PD for target lesion, a minimum 20% increase and a minimum 5 mm absolute increase in SOD compared to nadir, or PD for non-target lesion(s) o...
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: time from date of confirmation of the first response and the date of confirmation of the PD using independent reviewer assessment as per RECIST 1.1. BOR of CR and PR was confirmed by subsequent CR assessment and CR or PR assessment, respectively at least 4 weeks later. CR: disappearance of all measurable, non-measurable lesions and no unequivocal new le...
Number of Participants With Any Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) From the first dose of study drug to 30 days after the last dose (up to 3 years 5 months) TEAE is defined as an AE that emerged during time from the first dose of study drug to 30 days after the participant's last dose. An AE was any untoward medical occurrence in participant administered with an investigational product. An SAE was any untoward medical occurrence that at any dose: resulted in death; life threatening; requires participant hospital...
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) DOR: time from date of confirmation of the first response and the date of confirmation of the PD using independent reviewer assessment as per RECIST 1.1. BOR of CR and PR was confirmed by subsequent CR assessment and CR or PR assessment, respectively at least 4 weeks later. CR: disappearance of all measurable, non-measurable lesions and no unequivocal new le...
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) TTR was defined as the time from the first dose of the study drug to date of first observation of CR or PR using independent reviewer assessment based on RECIST 1.1. 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 \<10 mm. PR: at...
TTR Based on Investigator Assessment From the date of first dose until date of first observation of CR or PR (up to 3 years 4 months) TTR was defined as the time from the first dose of the study drug to date of first observation of CR or PR using investigator assessment based on RECIST 1.1. 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 \<10 mm. PR: at least a...
Trial Locations
- Locations (28)
1028 Eisai Trial Site
🇯🇵Yokohama, Kanagawa, Japan
1001 Eisai Trial Site
🇯🇵Chuo-ku, Tokyo, Japan
1011 Eisai Trial Site
🇯🇵Hiroshima, Japan
1024 Eisai Trial Site
🇯🇵Kumamoto, Japan
1019 Eisai Trial Site
🇯🇵Kobe, Hyogo, Japan
1025 Eisai Trial Site
🇯🇵Koto-ku, Tokyo, Japan
1009 Eisai Trial Site
🇯🇵Okayama, Japan
1010 Eisai Trial Site
🇯🇵Chiba, Japan
1016 Eisai Trial Site
🇯🇵Fukuoka, Japan
1021 Eisai Trial Site
🇯🇵Sendai, Miyagi, Japan
1003 Eisai Trial Site
🇯🇵Kyoto, Japan
1013 Eisai Trial Site
🇯🇵Osakasayama, Osaka, Japan
1026 Eisai Trial Site
🇯🇵Bunkyo-ku, Tokyo, Japan
1012 Eisai Trial Site
🇯🇵Fukuoka, Japan
1004 Eisai Trial Site
🇯🇵Nagoya, Aichi, Japan
1029 Eisai Trial Site
🇯🇵Nagoya, Aichi, Japan
1005 Eisai Trial Site
🇯🇵Tsukuba, Ibaraki, Japan
1002 Eisai Trial Site
🇯🇵Isehara, Kanagawa, Japan
1020 Eisai Trial Site
🇯🇵Ota, Gunma, Japan
1006 Eisai Trial Site
🇯🇵Suita, Osaka, Japan
1007 Eisai Trial Site
🇯🇵Sapporo, Hokkaido, Japan
1027 Eisai Trial Site
🇯🇵Suntou-gun, Shizuoka, Japan
1018 Eisai Trial Site
🇯🇵Yamagata, Japan
1023 Eisai Trial Site
🇯🇵Nagasaki, Japan
1015 Eisai Trial Site
🇯🇵Osaka, Japan
1017 Eisai Trial Site
🇯🇵Minato-ku, Tokyo, Japan
1022 Eisai Trial Site
🇯🇵Aomori, Japan
1008 Eisai Trial Site
🇯🇵Kyoto, Japan