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

Sponsor
Epizyme, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04762160
Collaborator
Swedish Cancer Institute (Other)
59
Enrollment
20
Locations
1
Arm
66.9
Anticipated Duration (Months)
3
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
59 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Feb 3, 2021
Anticipated Primary Completion Date :
Jul 1, 2026
Anticipated Study Completion Date :
Sep 1, 2026

Arms and Interventions

Arm Intervention/Treatment
Experimental: Tazmetostat in combination with rituximab

Tazemetostat 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.

Drug: Tazemetostat
Study Drug
Other Names:
  • EPZ-6438

    • Combination Product: Rituximab
    Partner Drug
    Other Names:
  • Rituximab Hyaluronidase

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Objective Response Rate [Assessed by Investigator and blinded independent review committee (IRC) at the following time points: Cycle 3, Cycle 6, Cycle 12, Cycle 18, and Cycle 24. Each cycle is 28 days.]

      Assess the objective response rate (ORR; complete response + partial response [CR + PR]), according to 2014 Lugano Classification, of Tazemetostat, in combination with Rituximab in subjects with relapsed/refractory follicular lymphoma and with wild-type (WT) EZH2 mutation status.

    Secondary Outcome Measures

    1. Incidence of Treatment-Emergent Adverse Events [Adverse events collected from time of signing informed consent to either 30 days after last dose of study drug or initiation of subsequent anticancer therapy, whichever occurs first]

      Evaluate safety of the combination of Tazemetostat and Rituximab by assessing incidence of adverse events (AEs)/serious adverse events (SAEs), events leading to discontinuation of study treatment or death, and change of vital signs, lab results, and physical exam findings from baseline. Outcome measured according to National Cancer (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

    2. Progression Free Survival [From first dose of study drug to earliest date of disease progression or death as assessed up to 24 months by an IRC]

      Estimate the median progression-free survival (PFS), per 2014 Lugano Classification, of Tazemetostat in combination with Rituximab at 2 years in subjects with R/R follicular lymphoma and WT EZH2 mutation status, and in the pooled group regardless of mutation status.

    3. Duration of Response [From earliest date of CR or PR to documented progression or death as assessed up to 24 months by an IRC]

      Estimate the duration of response (DOR).) per 2014 Lugano Classification.

    4. Response Rate in a subset of subjects with mutant (MT) EZH2 [Assessed at the following timepoints: Cycle 3, Cycle 6, Cycle 12, Cycle 18, and Cycle 24. Each cycle is 28 days.]

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

    5. Response rate in rituximab refractory subjects [Assessed at the following timepoints: Cycle 3, Cycle 6, Cycle 12, Cycle 18, and Cycle 24. Each cycle is 28 days.]

      Assess the ORR, according to 2014 Lugano Classification, in rituximab refractory subjects.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Men and women of 18 years of age and older

    2. Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol

    3. Eastern Cooperative Oncology Group (ECOG) score of 0 </=, 1 or 2

    4. Life expectancy (in the opinion of the investigator) of >3 months before enrollment

    5. 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

    6. Treatment recommended in accordance with the Groupe d'Etude des Lymphomes b Folliculaires (GELF) criteria

    7. Meet the following laboratory parameters:

    8. 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

    9. 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

    10. Hemoglobin ≥ 8 g/dL

    11. Serum alanine aminotransferase (AST) and aspartate aminotransferase (ALT) ≤ Incl3.0 x ULN, unless related to disease involvement

    12. Total bilirubin ≤ 1.5 x ULN, unless due to disease involvement, Gilbert's syndrome, or hemolytic anemia

    13. Estimated creatinine clearance (ie, estimated glomerular filtration rate [eGFR] using Cockcroft-Gault) ≥ 40 mL/min

    14. 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)

    15. 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

    16. Negative serologic or polymerase chain reaction (PCR) test results for acute or chronic hepatitis B virus (HBV) infection

    17. Negative test results for hepatitis C virus (HCV) and human immunodeficiency virus (HIV).

    18. 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.

    19. 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. .

    20. 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.

    Exclusion Criteria:

    1. Prior exposure to Tazemetostat or other inhibitor(s) of EZH2

    2. Grade 2b, mixed histology, or transformed FL

    3. Treatment with any of the following anticancer therapies within the timeframe of a specific treatment prior to first dose of study drug:

    4. Cytotoxic chemotherapy within 21 days

    5. Noncytotoxic chemotherapy (e.g. small molecule inhibitor) within 14 days

    6. Nitrosoureas within 6 weeks

    7. Prior immunotherapy within 4 weeks

    8. Radiotherapy- within 6 weeks from prior radioisotope therapy; within 12 weeks from 50% pelvic or total body irradiation

    9. Any investigational treatment within 4 weeks or at least 5 half lives, whichever is shorter

    10. History of solid organ transplant

    11. Major surgery within 4 weeks of the start of study treatment

    12. Thrombocytopenia, neutropenia, or anemia of Grade > 3 (per CTCAE v5.0 criteria) or any prior history of myeloid malignancies, including MDS/AML or MPN

    13. Prior history of T-LBL/T-ALL

    14. 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

    15. Subjects taking medications that are known strong cytochrome P450 (CYP)3A inhibitors and strong or moderate CYP3A inducers (including St. John's wort)

    16. Any uncontrolled illness

    17. History of clinically significant cardiovascular abnormalities

    18. History of clinically significant gastrointestinal (GI) conditions

    19. Other diagnosis of cancer that is likely to require treatment in the next 2 years

    20. Females who are pregnant or lactating/breastfeeding

    21. Received a live virus vaccination within 28 days of first dose of rituximab

    22. Concurrent participation in a separate investigational therapeutic study

    23. Psychiatric illness/social situations that would interfere with study compliance

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Alabama Oncology Birmingham Alabama United States 35223
    2 Compassionate Cancer Care Fountain Valley California United States 92708
    3 USOR/Rocky Mountain Cancer Centers Boulder Colorado United States 80303
    4 USOR/ Illinois Cancer Specialists Niles Illinois United States 60714
    5 XCancer/ Northwest Oncology & Hematology Rolling Meadows Illinois United States 60008
    6 Revive/Oakland Medical Group Farmington Hills Michigan United States 48336
    7 Revive/Hematology Oncology Associates of Rockland Sterling Heights Michigan United States 48314
    8 USOR/ NY Oncology Hematology Albany New York United States 12206
    9 East Carolina University Greenville North Carolina United States 27858
    10 USOR/ Oncology & Hematology Care Clinical Trials Cincinnati Ohio United States 45236
    11 XCancer/Dayton Physicians Network Kettering Ohio United States 45409
    12 XCancer/Tennessee Cancer Specialists Knoxville Tennessee United States 37909
    13 USOR/ Texas Oncology Austin Texas United States 78705
    14 USOR/Texas Oncology Dallas Texas United States 75230
    15 USOR/ Texas Oncology San Antonio Texas United States 78240
    16 USOR/ Texas Oncology Tyler Texas United States 75702
    17 USOR/Texas Oncology Weslaco Texas United States 78596
    18 USOR/Virginia Cancer Specialists Gainesville Virginia United States 20155
    19 USOR/Oncology & Hematology Associates of Southwest Virginia Roanoke Virginia United States 24014
    20 Swedish Cancer Institute Seattle Washington United States 98104

    Sponsors and Collaborators

    • Epizyme, Inc.
    • Swedish Cancer Institute

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Epizyme, Inc.
    ClinicalTrials.gov Identifier:
    NCT04762160
    Other Study ID Numbers:
    • EZH-1401
    First Posted:
    Feb 21, 2021
    Last Update Posted:
    Apr 1, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Epizyme, Inc.
    follicular lymphoma
    relapse follicular lymphoma
    refractory follicular lymphoma
    rituximab
    tazemetostat
    Additional relevant MeSH terms:
    Lymphoma
    Lymphoma, Follicular
    Rituximab

    Study Results

    No Results Posted as of Apr 1, 2022