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B-cell Lymphomas (Phase 1)Phase 1/2NCT01897571

Study of Tazemetostat as Single Agent in Solid Tumors or B-cell Lymphomas and in Combination With Prednisolone in DLBCL

A Phase 1/2 study testing Tazemetostat and Prednisolone in people with B-cell Lymphomas (Phase 1) and Advanced Solid Tumors (Phase 1), run by Epizyme, Inc. at 52 sites in 10 countries.

Completed

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

Official record
Search all trials

Trial summary

This is an open-label, multicenter, Phase 1/2 study of tazemetostat as a single agent in subjects with advanced solid tumors or with B-cell lymphomas and tazemetostat in combination with prednisolone in subjects with diffuse large B-cell lymphoma (DLBCL). Read more about this study

Who is it for?
Ages 16 years and older
What is being tested?
Tazemetostat and Prednisolone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
400 participants
Where
52 sitesin 10 countries
Study dates
13 Jun 2013to 2 Nov 2021
Phase
Phase 1/2
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 16 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Phase 1: Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Phase 2: ECOG performance status of 0 to 2.
  • Life expectancy of at least 3 months before starting tazemetostat.
  • Voluntary agreement to provide written informed consent and willing to adhere to all protocol requirements
  • Subjects with Hepatitis B or C are eligible on the condition that subjects have adequate liver function and are hepatitis B surface antigen negative and/or have undetectable hepatitis C virus (HCV) RNA.
  • Adequate renal and liver function
  • Phase 1: Males or females aged ≥ 16 years at time of informed consent. Phase 2: Males or females aged ≥ 18 years at the time of informed consent .
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  • Females must not be lactating or pregnant at screening or baseline as documented by a negative pregnancy test All females will be considered to be of childbearing potential unless they are postmenopausal (at least 12 months consecutive amenorrheic, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, total hysterectomy or bilateral oophorectomy, all with surgery at least 1 month before dose). Females of childbearing potential must not have had unprotected sexual intercourse within 30 days prior to study entry and must agree to use a highly effective method of contraception, from the last menstrual period prior to randomization, during Treatment Cycles, and for 6 months after the last final dose of study drug; any male partner must use a condom.
  • Male subjects must have had a successful vasectomy (with confirmed azoospermia) or they and their female partner must meet the criteria above (ie, not of childbearing potential or practicing highly effective contraception and use a condom throughout the study period and for 3 months after study drug discontinuation). Nonvasectomized male subjects must also agree to refrain from donating sperm from first dose of tazemetostat until 3 months following the last dose of tazemetostat
  • Phase 1 only: Histologically and/or cytologically confirmed advanced or metastatic solid tumor or B-cell lymphomas that have progressed after treatment with approved therapies or for which there are no standard therapies available.
  • Phase 2, Groups 1-6 only: Subjects must satisfy all of the following criteria:
  • Have histologically confirmed DLBCL (including primary mediastinal B-cell lymphoma), with relapsed or refractory disease following at least 2 lines of prior standard therapy, including alkylator/anthracycline (unless anthracycline-based chemotherapy is contraindicated)/anti-CD20-based therapy (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP] or equivalent) AND must be considered unable to benefit from intensification treatment with autologous hematopoietic stem cell transplantation (ASCT) as defined by meeting at least 1 of the following criteria:
  • Relapsed following, or refractory to, previous ASCT
  • Did not achieve at least a partial response to a standard salvage regimen (eg, rituximab, ifosfamide, carboplatin, and etoposide phosphate [R-ICE] or rituximab, dexamethasone, cytarabine, and cisplatin [R-DHAP])
  • Ineligible for intensification treatment due to age or significant comorbidity
  • Ineligible for intensification treatment due to failure to mobilize an acceptable number of hematopoietic stem cells
  • Refused intensification treatment and/or ASCT or
  • Have histologically confirmed Follicular Lymphoma (FL), all grades. Subjects may have relapsed/refractory disease following at least 2 standard prior systemic treatment regimens where at least 1 anti-CD20-based regimen was used. Subjects with prior radiotherapy will be included; however, radiotherapy alone will not be considered a systemic treatment regimen.
  • Have provided sufficient archival tumor tissue that has been successfully tested for EZH2 mutation status and cell of origin (DLBCL only)
  • Have measurable disease as defined by International Working Group-Non-Hodgkin's Lymphoma (IWG-NHL)

Who cannot join

  • Prior exposure to tazemetostat or other inhibitor(s) of EZH2.
  • Subjects with leptomeningeal metastases or brain metastases or history of previously treated brain metastases.
  • Has thrombocytopenia, neutropenia, or anemia of Grade ≥3 (per CTCAE 4.03 criteria) and any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS).
  • Has a prior history of T-cell lymphoblastic lymphoma(T-LBL) or T-cell lymphoblastic leukemia (T-ALL).
  • Subjects taking medications that are known strong CYP3A inhibitors and strong or moderate CYP3A inducers (including St. Johns Wort) 6. Subjects unwilling to remove Seville oranges, grapefruit juice and grapefruit from their diet.
  • Any unstable or unresolved prior treatment-related (i.e. chemotherapy, immunotherapy, radiotherapy) toxicities at time of enrollment.
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  • Major surgery within 4 weeks before the first dose of study drug. .
  • Inability to take oral medication, or malabsorption syndrome or any other uncontrolled gastrointestinal condition (e.g., nausea, diarrhea, or vomiting) that might impair the bioavailability of tazemetostat.
  • Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months of the first dose of study drug; or cardiac ventricular arrhythmia.
  • Venous thrombosis or pulmonary embolism within the last 3 months before starting tazemetostat.
  • Active infection requiring systemic therapy.
  • Immunocompromised patients, including patients known to be infected with human immunodeficiency virus (HIV).
  • Any other major illness that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in this study.
  • Females who are pregnant or breastfeeding.
  • Phase 2 only: Subjects with noncutaneous malignancies other than B-cell lymphomas. Exception: Subjects with another malignancy who have been disease-free for 5 years, or subjects with a history of a completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.

Trial locations and contacts

52 sites in 10 countries.

52 sites in 10 countries

France13 sites

  • Study site

    Bordeaux

  • Study site

    Caen

  • Study site

    Créteil

  • Study site

    Lille

  • Study site

    Lyon

  • Study site

    Marseille

  • Study site

    Montpellier

  • Study site

    Nantes

  • Study site

    Paris

  • Study site

    Pierre-Bénite

  • Study site

    Rennes

  • Study site

    Rouen

  • Study site

    Villejuif

Other trials in France

United States12 sites

  • Study site

    Ann Arbor, Michigan, 48109

  • Study site

    Aurora, Colorado, 80012

  • Study site

    Birmingham, Alabama, 35294

  • Study site

    Duarte, California, 91010

  • Study site

    Fairfax, Virginia, 22031

  • Study site

    Houston, Texas, 77030

  • Study site

    New York, New York, 10065

  • Study site

    Ocala, Florida, 34471

  • Study site

    San Antonio, Texas, 78217

  • Study site

    Santa Barbara, California, 93105

  • Study site

    Seattle, Washington, 98122

  • Study site

    Washington D.C., District of Columbia, 20057

Other trials in United States

Ukraine9 sites

  • Study site

    Chernivtsi

  • Study site

    Dnipro

  • Study site

    Ivano-Frankivsk

  • Study site

    Kharkiv

  • Study site

    Kyiv

  • Study site

    Mykolayiv

  • Study site

    Uzhhorod

  • Study site

    Zaporizhzhya

  • Study site

    Zhytomyr

Other trials in Ukraine

Poland4 sites

  • Study site

    Krakow

  • Study site

    Lublin

  • Study site

    Poznan

  • Study site

    Warsaw

Other trials in Poland

United Kingdom4 sites

  • Study site

    Glasgow

  • Study site

    London

  • Study site

    Manchester

  • Study site

    Southampton

Other trials in United Kingdom

Australia3 sites

  • Study site

    Clayton

  • Study site

    Geelong

  • Study site

    Melbourne

Other trials in Australia

Canada2 sites

  • Study site

    Montreal

  • Study site

    Toronto

Other trials in Canada

Germany2 sites

  • Study site

    Göttingen

  • Study site

    Münster

Other trials in Germany

Italy2 sites

  • Study site

    Bologna

  • Study site

    Naples

Other trials in Italy

Taiwan1 site

  • Study site

    Taipei

Other trials in Taiwan

About this study

Official title: An Open-Label, Multicenter, Phase 1/2 Study of Tazemetostat as a Single Agent in Subjects With Advanced Solid Tumors or With B-cell Lymphomas and Tazemetostat in Combination With Prednisolone in Subjects With Diffuse Large B Cell Lymphoma

This is an open-label, multicenter, Phase 1/2 study of tazemetostat as a single agent in subjects with advanced solid tumors or with B-cell lymphomas and tazemetostat in combination with prednisolone in subjects with diffuse large B-cell lymphoma (DLBCL).

Read the detailed description

This is a multicenter, open-label, Phase 1/2 study conducted in two parts: The Phase 1 part comprised dose escalation and expansion to establish the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) when tazemetostat was given twice daily (BID) orally on a continuous basis. Additionally, in separate cohorts in Phase 1, the effect of food on the bioavailability of tazemetostat as well as the drug-drug interaction (DDI) potential of tazemetostat were evaluated. The Phase 2 part was initiated once the RP2D was established. Phase 2 enrolled subjects with relapsed/ refectory (R/R) DLBCL (Cohorts 1-3 and 6) and subjects with R/R FL (Cohorts 4 and 5) for the determination of efficacy and safety of tazemetostat monotherapy (Cohorts 1-5) and of tazemetostat in combination with prednisolone (Cohort 6) with placement determined by centrally confirmed histology, cell of origin (COO), and enhancer of zeste homologue 2 (EZH2) mutation status.

Being tested
Tazemetostat, Prednisolone
Keywords
Epizyme, Tazverik, Tazemetostat (EPZ-6438)
Medical subject headings
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

    Also called EPZ-6438, E7438

    Patients who received 800 mg of tazemetostat, BID, administered in continuous 28-day cycles.

  • PrednisoloneDrug

    Also called Pediapred, Omnipred, Pred Mild, Pred Forte,

    Patients who received 40 mg/m^2 prednisolone once daily on Days 1-5 and 15-19 of Cycles 1-4.

  • TazemetostatDrug

    Also called EPZ-6438, E7438

    Patients who received 100 mg to 1600 mg of tazemetostat, BID, administered in continuous 28-day cycles.

Study groups in NCT01897571
Study groupRoleWhat they receive
Phase 1ExperimentalPatients in the Phase 1 portion of the study.
Receives: Drug: Tazemetostat
Phase 2 Group 1: Tazemetostat in R/R FL with Mutant EZH2ExperimentalPatients with R/R FL with mutant EZH2 treated with tazemetostat as a single agent in Phase 2 of the study.
Receives: Drug: Tazemetostat
Phase 2 Group 2: Tazemetostat in R/R FL with Wild-Type EZH2ExperimentalPatients with R/R FL with wild-type EZH2 treated with tazemetostat as a single agent in Phase 2 of the study.
Receives: Drug: Tazemetostat
Phase 2 Group 3: Tazemetostat in R/R DLBCLExperimentalPatients with R/R DLBCL treated with tazemetostat as a single agent or tazemetostat in combination with prednisolone in Phase 2 of the study.
Receives: Drug: Tazemetostat; Drug: Prednisolone

What is being measured

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

  1. Recommended Phase 2 Dose (RP2D) of Tazemetostat as a Single-Agent and in Combination With Prednisolone (Phase 1 Only)

    Recommended Phase 2 dose (RP2D) of tazemetostat as administered orally twice daily (BID), continuously in 28-day cycles in subjects with advanced solid tumors or with relapsed and/or refractory B cell lymphomas as determined by incidence, seriousness, toxicity grade, and relatedness of treatment emergent dose limiting toxicities

    Measured: The first 28-day cycle of therapy

  2. Objective Response Rate (ORR; Complete Response + Partial Response [CR + PR]) (Phase 2)

    Number of patients achieving an objective response (CR or PR)/number of patients treated x 100%. ORR was calculated as the percentage of patients with a confirmed complete response (CR) or partial response (PR) relative to the total number of patients in the analysis population per response evaluation criteria in solid tumors (RECIST) version (v)1.1. Complete Response (CR) was defined as disappearance of all target and non-target lesions and any pathological lymph nodes must be <10 millimeter (mm) in the short axis. Partial Response (PR) was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters.

    Measured: Radiologic tumor assessments performed at baseline(within 28 days before start of study treatment)and every 8 weeks during Cycles 2 to 6,and then every 12 weeks thereafter until confirmed disease progression (PD)/death,a maximum of approximately 82 months

Secondary outcomes (2)

  1. Duration of Response for Tazemetostat as a Single Agent or in Combination With Prednisolone (Phase 2 Only)

    The time (in months) from the date of the initial response (CR or PR, whichever was first) until the date of the first documented disease progression per an Independent Review Committee (for Groups 1 and 2), per Investigator (Group 3), or death due to any cause. Patients who were alive and progression free at the time of the analysis were censored at the last date where the patient was known to be in response. Note: the DOR was censored, meaning data collection was stopped early for analysis, making the top limit of the 95% confidence interval not estimable (NE). Per RECIST v.1.0, CR was defined as disappearance of all target and non-target lesions and any pathological lymph nodes must be <10 mm in the short axis. The PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters.

    Measured: Radiologic tumor assessments performed at baseline (within 28 days before start of study treatment) and every 8 weeks during Cycles 2 to 6, and then every 12 weeks thereafter until confirmed PD/death, a maximum of approximately 82 months

  2. Progression Free Survival for Tazemetostat as a Single Agent or in Combination With Prednisolone (Phase 2 Only)

    The time (in months) from the date of first dose of tazemetostat until the earliest date of disease progression or death from any cause. Per RECIST v1.0, CR was defined as disappearance of all target and non-target lesions and any pathological lymph nodes must be <10 mm in the short axis. The PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters.

    Measured: Radiologic tumor assessments performed at baseline (within 28 days before start of study treatment) and every 8 weeks during Cycles 2 to 6, and then every 12 weeks thereafter until confirmed PD/death, a maximum of approximately 82 months

Timeline

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

  1. First posted12 Jul 2013 (estimated)
  2. Study start13 Jun 2013
  3. Primary completion24 Aug 2021
  4. Study completion2 Nov 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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
400 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01897571
Sponsor's protocol ID
E7438-G000-101
Other IDs
2012-004083-21
Status last verified
Mar 2024
First submitted
21 Jun 2013
Last updated
26 Mar 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Alfaifi A, Bahashwan S, Alsaadi M, Ageel AH, Ahmed HH, Fatima K, Malhan H, Qadri I, Almehdar H. Advancements in B-Cell Non-Hodgkin's Lymphoma: From Signaling Pathways to Targeted Therapies. Adv Hematol. 2024 Nov 12;2024:5948170. doi: 10.1155/2024/5948170. eCollection 2024.

    PubMed 39563886

  • Bosch F, Kuruvilla J, Vassilakopoulos TP, Maio DD, Wei MC, Zumofen MB, Nastoupil LJ. Indirect Treatment Comparisons of Mosunetuzumab With Third- and Later-Line Treatments for Relapsed/Refractory Follicular Lymphoma. Clin Lymphoma Myeloma Leuk. 2024 Feb;24(2):105-121. doi: 10.1016/j.clml.2023.09.007. Epub 2023 Sep 28.

    PubMed 37981564

  • Morschhauser F, Tilly H, Chaidos A, McKay P, Phillips T, Assouline S, Batlevi CL, Campbell P, Ribrag V, Damaj GL, Dickinson M, Jurczak W, Kazmierczak M, Opat S, Radford J, Schmitt A, Yang J, Whalen J, Agarwal S, Adib D, Salles G. Tazemetostat for patients with relapsed or refractory follicular lymphoma: an open-label, single-arm, multicentre, phase 2 trial. Lancet Oncol. 2020 Nov;21(11):1433-1442. doi: 10.1016/S1470-2045(20)30441-1. Epub 2020 Oct 6.

    PubMed 33035457

  • Italiano A, Soria JC, Toulmonde M, Michot JM, Lucchesi C, Varga A, Coindre JM, Blakemore SJ, Clawson A, Suttle B, McDonald AA, Woodruff M, Ribich S, Hedrick E, Keilhack H, Thomson B, Owa T, Copeland RA, Ho PTC, Ribrag V. Tazemetostat, an EZH2 inhibitor, in relapsed or refractory B-cell non-Hodgkin lymphoma and advanced solid tumours: a first-in-human, open-label, phase 1 study. Lancet Oncol. 2018 May;19(5):649-659. doi: 10.1016/S1470-2045(18)30145-1. Epub 2018 Apr 9.

    PubMed 29650362

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Tazemetostat and Prednisolone in people with B-cell Lymphomas (Phase 1) and Advanced Solid Tumors (Phase 1), run by Epizyme, Inc. at 52 sites in 10 countries.

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 19 inclusion and 15 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 26 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 52 sites in France, United States, Ukraine, Poland, United Kingdom and 5 more countries. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 4 Aug 2023). 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?

Recommended Phase 2 Dose (RP2D) of Tazemetostat as a Single-Agent and in Combination With Prednisolone (Phase 1 Only) (time frame: The first 28-day cycle of therapy). 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 NCT01897571, which also lists 4 linked publications.

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 26 Mar 2024.

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