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Relapsed or Refractory B-cell Non-Hodgkin's LymphomaPhase 2NCT03456726

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

A Phase 2 study testing Tazemetostat in people with Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma, run by Eisai Co., Ltd. at 28 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 20 years and older
What is being tested?
Tazemetostat
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
28 sitesJapan
Study dates
9 Apr 2018to 17 Dec 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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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
  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

28 sites in 1 country.

28 sites in 1 country

Japan28 sites
  • 1022 Eisai Trial Site

    Aomori

  • 1026 Eisai Trial Site

    Bunkyo-ku, Tokyo

  • 1010 Eisai Trial Site

    Chiba

  • 1001 Eisai Trial Site

    Chuo-ku, Tokyo

  • 1012 Eisai Trial Site

    Fukuoka

  • 1016 Eisai Trial Site

    Fukuoka

  • 1011 Eisai Trial Site

    Hiroshima

  • 1002 Eisai Trial Site

    Isehara, Kanagawa

  • 1019 Eisai Trial Site

    Kobe, Hyōgo

  • 1025 Eisai Trial Site

    Koto-ku, Tokyo

  • 1024 Eisai Trial Site

    Kumamoto

  • 1003 Eisai Trial Site

    Kyoto

  • 1008 Eisai Trial Site

    Kyoto

  • 1017 Eisai Trial Site

    Minato-ku, Tokyo

  • 1023 Eisai Trial Site

    Nagasaki

  • 1004 Eisai Trial Site

    Nagoya, Aichi-ken

  • 1029 Eisai Trial Site

    Nagoya, Aichi-ken

  • 1009 Eisai Trial Site

    Okayama

  • 1015 Eisai Trial Site

    Osaka

  • 1020 Eisai Trial Site

    Ōta, Gunma

  • 1007 Eisai Trial Site

    Sapporo, Hokkaido

  • 1013 Eisai Trial Site

    Sayama, Osaka

  • 1021 Eisai Trial Site

    Sendai, Miyagi

  • 1006 Eisai Trial Site

    Suita, Osaka

  • 1027 Eisai Trial Site

    Suntou-gun, Shizuoka

  • 1005 Eisai Trial Site

    Tsukuba, Ibaraki

  • 1018 Eisai Trial Site

    Yamagata

  • 1028 Eisai Trial Site

    Yokohama, Kanagawa

Other trials in Japan

About this study

Official title: A Phase 2 Study of Tazemetostat in Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma With EZH2 Gene Mutation

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.

Being tested
Tazemetostat
Keywords
EZH2 gene mutation, Tazemetostat, Diffuse large B-cell lymphoma, Follicular lymphoma
Medical subject headings
Recurrence, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TazemetostatDrug

    Tazemetostat will be provided as a 200 mg oral tablet.

Study groups in NCT03456726
Study groupRoleWhat they receive
FL with EZH2 gene mutationExperimentalParticipants 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.
Receives: Drug: Tazemetostat
DLBCL with EZH2 gene mutationExperimentalParticipants 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.
Receives: Drug: Tazemetostat

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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.

    Measured: 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)
  1. Progression-free Survival (PFS) Based on Independent Reviewer Assessment

    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 lesion(s) or unequivocal new lesion(s). Nadir: Lowest measure SOD of target lesion at any time point from baseline onward. The 95% CI was calculated using Kaplan-Meier estimate.

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

  2. PFS Based on Investigator Assessment

    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) or unequivocal new lesion(s). Nadir: Lowest measure SOD of target lesion at any time point from baseline onward. The 95% CI was calculated using Kaplan-Meier estimate.

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

  3. Duration of Response (DOR) Based on Independent Reviewer Assessment

    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 lesions. Any pathological lymph nodes had to be reduced in short axis to <10 mm. PR: at least 30% decrease in SOD of target lesions, taking as reference the baseline SOD, there are no unequivocal new lesions, and no progression of non-target disease. PD for target lesion, a minimum 20% increase and a minimum 5mm absolute increase in SOD compared to nadir, or PD for non-target lesions or unequivocal new lesions. Nadir: Lowest measure SOD of target lesions at any time point from baseline onward. The 95% CI was calculated using Kaplan-Meier estimate.

    Measured: 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)

  4. DOR Based on Investigator Assessment

    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 lesions. Any pathological lymph nodes had to be reduced in short axis to <10 mm. PR: at least 30% decrease in SOD of target lesions, taking as reference the baseline SOD, there are no unequivocal new lesions, and no progression of non-target disease. PD for target lesion, a minimum 20% increase and a minimum 5mm absolute increase in SOD compared to nadir, or PD for non-target lesions or unequivocal new lesions. Nadir: Lowest measure SOD of target lesions at any time point from baseline onward. The 95% CI was calculated using Kaplan-Meier estimate.

    Measured: 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)

  5. Time to Response (TTR) Based on Independent Reviewer Assessment

    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 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.

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

  6. TTR Based on Investigator Assessment

    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 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.

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

  7. Number of Participants With Any Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    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 hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug).

    Measured: From the first dose of study drug to 30 days after the last dose (up to 3 years 5 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Mar 2018
  2. Study start9 Apr 2018
  3. Primary completion17 Dec 2021
  4. Study completion17 Dec 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03456726
Sponsor's protocol ID
E7438-J081-206
Status last verified
Apr 2021
First submitted
6 Mar 2018
Last updated
16 Dec 2022
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 39179948

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tazemetostat in people with Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma, run by Eisai Co., Ltd. at 28 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Dec 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) Based on Independent Reviewer Assessment (time frame: From date of first dose of study drug administration to date of PD or death, whichever occurred first (up to 3 years 4 months)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03456726, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2022.

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