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Follicular LymphomaPhase 2NCT04762160

SYMPHONY-2, A Trial to Examine Combination of Tazemetostat With Rituximab in Subjects With Relapsed/Refractory Follicular Lymphoma

A Phase 2 study testing Tazemetostat and Rituximab in people with Follicular Lymphoma, run by Epizyme, Inc. at 20 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This study evaluates the safety and efficacy of combining the EZH2 inhibitor tazemetostat with rituximab in R/R FL subjects previously treated with at least 2 standard prior systemic treatment regimens where at least 1 anti-CD20-based regimen was used. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Follicular Lymphoma
What is being tested?
Tazemetostat and Rituximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
20 sitesUnited States
Study dates
15 Dec 2020to 22 Mar 2022
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Men and women of 18 years of age and older
  • Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol
  • Eastern Cooperative Oncology Group (ECOG) score of 0 </=, 1 or 2
  • Life expectancy (in the opinion of the investigator) of >3 months before enrollment
  • Have histologically confirmed FL, Grade 1 to 3a. Subjects may have R/R disease following at least 2 standard prior systemic treatment regimens where at least 1 anti- CD20-based regimen was used
  • Treatment recommended in accordance with the Groupe d'Etude des Lymphomes b Folliculaires (GELF) criteria
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  • Meet the following laboratory parameters:
  • Absolute neutrophil count (ANC) ≥ 750 cells/μL (0.75 x 109/L), or ≥ 500 cells/μL (0.50 x 109/L) in subjects with documented bone marrow involvement
  • Platelet count ≥ 50,000 cells/μL (50 x 109/L), or ≥ 30,000 cells/μL (30 x 109/L) in subjects with documented bone marrow involvement, and without transfusion dependence
  • Hemoglobin ≥ 8 g/dL
  • Serum alanine aminotransferase (AST) and aspartate aminotransferase (ALT) ≤ Incl3.0 x ULN, unless related to disease involvement
  • Total bilirubin ≤ 1.5 x ULN, unless due to disease involvement, Gilbert's syndrome, or hemolytic anemia
  • Estimated creatinine clearance (ie, estimated glomerular filtration rate [eGFR] using Cockcroft-Gault) ≥ 40 mL/min
  • At least one bi-dimensionally measurable nodal lesion > 1.5 cm in its longest diameter by computed tomography (CT) scan or magnetic resonance imaging (MRI)
  • Any clinically significant toxicity related to a prior anticancer treatment (ie, chemotherapy, immunotherapy, and/or radiotherapy), except for alopecia, either resolved to ≤ Grade 1 per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 or is clinically stable and no longer clinically significant
  • Negative serologic or polymerase chain reaction (PCR) test results for acute or chronic hepatitis B virus (HBV) infection
  • Negative test results for hepatitis C virus (HCV) and human immunodeficiency virus (HIV).
  • Females of childbearing potential (FCBP) must have a negative serum pregnancy test (beta-human chorionic gonadotropin [β-hCG] test with a minimum sensitivity of 25 mIU/mL or equivalent units of β-hCG) at screening and within 24 hours prior to the first dose of study drug.
  • FCBP must either practice complete abstinence or agree to use a highly effective method of contraception beginning at least 28 days prior to the first dose of study drug, during study treatment (including during dose interruptions), for 6 months after tazemetostat discontinuation, and for 12 months after rituximab discontinuation. .
  • Male subjects must have had a successful vasectomy (with medically confirmed azoospermia) OR must either practice complete abstinence or agree to use a latex or synthetic condom during sexual contact with a FCBP from the first dose of study drug, during study treatment (including during dose interruptions), and for 3 months after study drug discontinuation.

Who cannot join

  • Prior exposure to Tazemetostat or other inhibitor(s) of EZH2
  • Grade 2b, mixed histology, or transformed FL
  • Treatment with any of the following anticancer therapies within the timeframe of a specific treatment prior to first dose of study drug:
  • Cytotoxic chemotherapy within 21 days
  • Noncytotoxic chemotherapy (e.g. small molecule inhibitor) within 14 days
  • Nitrosoureas within 6 weeks
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  • Prior immunotherapy within 4 weeks
  • Radiotherapy- within 6 weeks from prior radioisotope therapy; within 12 weeks from 50% pelvic or total body irradiation
  • Any investigational treatment within 4 weeks or at least 5 half lives, whichever is shorter
  • History of solid organ transplant
  • Major surgery within 4 weeks of the start of study treatment
  • Thrombocytopenia, neutropenia, or anemia of Grade > 3 (per CTCAE v5.0 criteria) or any prior history of myeloid malignancies, including MDS/AML or MPN
  • Prior history of T-LBL/T-ALL
  • Unwillingness to exclude grapefruit juice-containing products, Seville oranges, and grapefruits from the diet and/ or consumed within 1 week of the first dose of study drug
  • Subjects taking medications that are known strong cytochrome P450 (CYP)3A inhibitors and strong or moderate CYP3A inducers (including St. John's wort)
  • Any uncontrolled illness
  • History of clinically significant cardiovascular abnormalities
  • History of clinically significant gastrointestinal (GI) conditions
  • Other diagnosis of cancer that is likely to require treatment in the next 2 years
  • Females who are pregnant or lactating/breastfeeding
  • Received a live virus vaccination within 28 days of first dose of rituximab
  • Concurrent participation in a separate investigational therapeutic study
  • Psychiatric illness/social situations that would interfere with study compliance

Trial locations and contacts

20 sites in 1 country.

20 sites in 1 country

United States20 sites

  • USOR/ NY Oncology Hematology

    Albany, New York, 12206

  • USOR/ Texas Oncology

    Austin, Texas, 78705

  • Alabama Oncology

    Birmingham, Alabama, 35223

  • USOR/Rocky Mountain Cancer Centers

    Boulder, Colorado, 80303

  • USOR/ Oncology & Hematology Care Clinical Trials

    Cincinnati, Ohio, 45236

  • USOR/Texas Oncology

    Dallas, Texas, 75230

  • Revive/Oakland Medical Group

    Farmington Hills, Michigan, 48336

  • Compassionate Cancer Care

    Fountain Valley, California, 92708

  • USOR/Virginia Cancer Specialists

    Gainesville, Virginia, 20155

  • East Carolina University

    Greenville, North Carolina, 27858

  • XCancer/Dayton Physicians Network

    Kettering, Ohio, 45409

  • XCancer/Tennessee Cancer Specialists

    Knoxville, Tennessee, 37909

  • USOR/ Illinois Cancer Specialists

    Niles, Illinois, 60714

  • USOR/Oncology & Hematology Associates of Southwest Virginia

    Roanoke, Virginia, 24014

  • XCancer/ Northwest Oncology & Hematology

    Rolling Meadows, Illinois, 60008

  • USOR/ Texas Oncology

    San Antonio, Texas, 78240

  • Swedish Cancer Institute

    Seattle, Washington, 98104

  • Revive/Hematology Oncology Associates of Rockland

    Sterling Heights, Michigan, 48314

  • USOR/ Texas Oncology

    Tyler, Texas, 75702

  • USOR/Texas Oncology

    Weslaco, Texas, 78596

Other trials in United States

About this study

Official title: SYMPHONY-II: A Phase II Open-Label, Multicenter Trial of Oral Tazemetostat in Combination With Rituximab in Subjects With Relapsed/Refractory Follicular Lymphoma

This study evaluates the safety and efficacy of combining the EZH2 inhibitor tazemetostat with rituximab in R/R FL subjects previously treated with at least 2 standard prior systemic treatment regimens where at least 1 anti-CD20-based regimen was used.

Read the detailed description

This is a phase 2, multicenter, open-label study of oral tazemetostat in combination with rituximab in subjects with relapsed or refractory (R/R) follicular lymphoma (FL). This study is designed to evaluate the safety and efficacy of tazemetostat in combination with rituximab in subjects previously treated with at least 2 standard prior systemic treatment regimens where at least 1 anti-CD20-based regimen was used, and used and features early futility stopping to maintain subject safety.

Being tested
Tazemetostat, Rituximab
Keywords
follicular lymphoma, relapse follicular lymphoma, refractory follicular lymphoma, rituximab, tazemetostat
Medical subject headings
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

    Study Drug

  • RituximabCombination product

    Also called Rituximab Hyaluronidase

    Partner Drug

Study groups in NCT04762160
Study groupRoleWhat they receive
Tazmetostat in combination with rituximabExperimentalTazemetostat 800 mg BID is administered daily starting on Cycle 1 Day 1 (C1D1). Tazemetostat will be administered from C1D1 to the end of Cycle 24, for 24 months of therapy or until disease progression, unacceptable toxicity, or withdrawal of consent. Rituximab will be administered by either subcutaneous injection or IV infusion according to the regional product prescribing information, labeling and institutional guidelines. Rituximab will be administered at a dose of 375 mg/m2 on Day 1, 8, 15, and 22 of Cycle 1, and then on Day 1 of Cycles 3 through 6, accounting for an additional 4 doses, i.e., a total of 8 doses of rituximab in 6 cycles.
Receives: Drug: Tazemetostat; Combination Product: Rituximab

What is being measured

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

  1. Objective Response Rate (ORR)

    ORR was defined as the percentage of participants with WT EZH2 status who achieved a complete response (CR) or partial response (PR) according to the 2014 Lugano Classification as assessed by investigator and blinded independent review committee (IRC). CR = complete metabolic response per positron emission tomography-computed tomography (PET-CT) based response or complete radiologic response per CT-based response. PR = partial metabolic response per PET-CT-based response or partial remission per CT-based response.

    Measured: Planned to be assessed during Cycles 3, 6, 12, 18, and 24.

Secondary outcomes (4)

  1. Progression Free Survival (PFS)

    PFS was defined as the time from first dose of study drug to the time of the earliest date of CR or PR per the 2014 Lugano Classification or death, whichever occurred first, as assessed by an IRC. CR= complete metabolic response per PET-CT based response or complete radiologic response per CT-based response. PR= partial metabolic response per PET-CT-based response or partial remission per CT-based response.

    Measured: Planned to be assessed from first dose of study drug to earliest date of disease progression or death as assessed up to 24 months by an IRC

  2. Duration of Response (DOR)

    DOR was defined as the time from the earliest date of CR or PR per the 2014 Lugano Classification to documented progression or death, whichever comes first, as assessed by an IRC. CR= complete metabolic response per PET-CT based response or complete radiologic response per CT-based response. PR= partial metabolic response per PET-CT-based response or partial remission per CT-based response.

    Measured: Planned to be assessed from earliest date of CR or PR to documented progression or death as assessed up to 24 months by an IRC

  3. ORR in a Subset of Participants With MT EZH2

    ORR was assessed according to 2014 Lugano Classification, in the pooled group regardless of mutation status and in a subset of participants with MT EZH2.

    Measured: Planned to be assessed at the following timepoints: Cycles 3, 6, 12, 18, and 24

  4. ORR in Rituximab Refractory Participants

    ORR was assessed according to 2014 Lugano Classification, in rituximab refractory participants.

    Measured: Planned to be assessed at the following timepoints: Cycle 3, Cycle 6, Cycle 12, Cycle 18, and Cycle 24.

Timeline

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

  1. First posted21 Feb 2021
  2. Study start15 Dec 2020
  3. Primary completion22 Mar 2022
  4. Study completion22 Mar 2022

Why it stopped: Decision to terminate EZH-1401 was solely due to company business decision.

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04762160
Sponsor's protocol ID
EZH-1401
Status last verified
Mar 2024
First submitted
5 Feb 2021
Last updated
25 Mar 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tazemetostat and Rituximab in people with Follicular Lymphoma, run by Epizyme, Inc. at 20 sites in United States.

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 20 inclusion and 23 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: stopped early, as of the sponsor's last update on 25 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 20 sites in United States. 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 21 Nov 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?

Objective Response Rate (ORR) (time frame: Planned to be assessed during Cycles 3, 6, 12, 18, and 24.). 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 NCT04762160.

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 25 Mar 2024.

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