Clinical trial NCT03456726: Study of Tazemetostat in Participants With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma With EZH2 Gene Mutation
Official title: A Phase 2 Study of Tazemetostat in Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma With EZH2 Gene Mutation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma
Keywords: EZH2 gene mutation
Tazemetostat
Diffuse large B-cell lymphoma
Follicular lymphoma
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2018-03-07
Enrollment: 20
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Objective Response Rate (ORR) Based on Independent Reviewer Assessment
timeFrame: From date of first dose of study drug administration to date of PD or death, whichever occurred first (up to 3 years 4 months)
measure: ORR Based on Investigator Assessment
timeFrame: 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:
measure: Progression-free Survival (PFS) Based on Independent Reviewer Assessment
timeFrame: From date of first dose of study drug administration to date of PD or death, whichever occurred first (up to 3 years 4 months)
measure: PFS Based on Investigator Assessment
timeFrame: From date of first dose of study drug administration to date of PD or death, whichever occurred first (up to 3 years 4 months)
measure: Duration of Response (DOR) Based on Independent Reviewer Assessment
timeFrame: 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)
measure: DOR Based on Investigator Assessment
timeFrame: 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)
measure: Time to Response (TTR) Based on Independent Reviewer Assessment
timeFrame: From the date of first dose until date of first observation of CR or PR (up to 3 years 4 months)
measure: TTR Based on Investigator Assessment
timeFrame: From the date of first dose until date of first observation of CR or PR (up to 3 years 4 months)
measure: Number of Participants With Any Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: From the first dose of study drug to 30 days after the last dose (up to 3 years 5 months)
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: 1004 Eisai Trial Site
state: Aichi
city: Nagoya
country: Japan
facility: 1029 Eisai Trial Site
state: Aichi
city: Ota
country: Japan
facility: 1020 Eisai Trial Site
state: Gunma
city: Sapporo
country: Japan
facility: 1007 Eisai Trial Site
state: Hokkaido
city: Kobe
country: Japan
facility: 1019 Eisai Trial Site
state: Hyogo
city: Tsukuba
country: Japan
facility: 1005 Eisai Trial Site
state: Ibaraki
city: Isehara
country: Japan
facility: 1002 Eisai Trial Site
state: Kanagawa
city: Yokohama
country: Japan
facility: 1028 Eisai Trial Site
state: Kanagawa
city: Sendai
country: Japan
facility: 1021 Eisai Trial Site
state: Miyagi
city: Osakasayama
country: Japan
facility: 1013 Eisai Trial Site
state: Osaka
city: Suita
country: Japan
facility: 1006 Eisai Trial Site
state: Osaka
city: Suntou-gun
country: Japan
facility: 1027 Eisai Trial Site
state: Shizuoka
city: Bunkyo-ku
country: Japan
facility: 1026 Eisai Trial Site
state: Tokyo
city: Chuo-ku
country: Japan
facility: 1001 Eisai Trial Site
state: Tokyo
city: Koto-ku
country: Japan
facility: 1025 Eisai Trial Site
state: Tokyo
city: Minato-ku
country: Japan
facility: 1017 Eisai Trial Site
state: Tokyo
city: Aomori
country: Japan
facility: 1022 Eisai Trial Site
city: Chiba
country: Japan
facility: 1010 Eisai Trial Site
city: Fukuoka
country: Japan
facility: 1012 Eisai Trial Site
city: Fukuoka
country: Japan
facility: 1016 Eisai Trial Site
city: Hiroshima
country: Japan
facility: 1011 Eisai Trial Site
city: Kumamoto
country: Japan
facility: 1024 Eisai Trial Site
city: Kyoto
country: Japan
facility: 1003 Eisai Trial Site
city: Kyoto
country: Japan
facility: 1008 Eisai Trial Site
city: Nagasaki
country: Japan
facility: 1023 Eisai Trial Site
city: Okayama
country: Japan
facility: 1009 Eisai Trial Site
city: Osaka
country: Japan
facility: 1015 Eisai Trial Site
city: Yamagata
country: Japan
facility: 1018 Eisai Trial Site
Study officials:
References: