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

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ClinicalTrials.gov Identifier: NCT04762160
Recruitment Status : Recruiting
First Posted : February 21, 2021
Last Update Posted : April 1, 2022
Sponsor:
Collaborator:
Swedish Cancer Institute
Information provided by (Responsible Party):
Epizyme, Inc.

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
Follicular Lymphoma Drug: Tazemetostat Combination Product: Rituximab 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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : February 3, 2021
Estimated Primary Completion Date : July 2026
Estimated Study Completion Date : September 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

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 Name: EPZ-6438

Combination Product: Rituximab
Partner Drug
Other Name: Rituximab Hyaluronidase




Primary Outcome Measures :
  1. Objective Response Rate [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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:

    1. 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
    2. 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
    3. Hemoglobin ≥ 8 g/dL
    4. Serum alanine aminotransferase (AST) and aspartate aminotransferase (ALT) ≤ Incl3.0 x ULN, unless related to disease involvement
    5. Total bilirubin ≤ 1.5 x ULN, unless due to disease involvement, Gilbert's syndrome, or hemolytic anemia
    6. Estimated creatinine clearance (ie, estimated glomerular filtration rate [eGFR] using Cockcroft-Gault) ≥ 40 mL/min
  8. 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)
  9. 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
  10. Negative serologic or polymerase chain reaction (PCR) test results for acute or chronic hepatitis B virus (HBV) infection
  11. Negative test results for hepatitis C virus (HCV) and human immunodeficiency virus (HIV).
  12. 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.
  13. 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. .
  14. 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:

    1. Cytotoxic chemotherapy within 21 days
    2. Noncytotoxic chemotherapy (e.g. small molecule inhibitor) within 14 days
    3. Nitrosoureas within 6 weeks
    4. Prior immunotherapy within 4 weeks
    5. Radiotherapy- within 6 weeks from prior radioisotope therapy; within 12 weeks from 50% pelvic or total body irradiation
    6. Any investigational treatment within 4 weeks or at least 5 half lives, whichever is shorter
  4. History of solid organ transplant
  5. Major surgery within 4 weeks of the start of study treatment
  6. Thrombocytopenia, neutropenia, or anemia of Grade > 3 (per CTCAE v5.0 criteria) or any prior history of myeloid malignancies, including MDS/AML or MPN
  7. Prior history of T-LBL/T-ALL
  8. 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
  9. Subjects taking medications that are known strong cytochrome P450 (CYP)3A inhibitors and strong or moderate CYP3A inducers (including St. John's wort)
  10. Any uncontrolled illness
  11. History of clinically significant cardiovascular abnormalities
  12. History of clinically significant gastrointestinal (GI) conditions
  13. Other diagnosis of cancer that is likely to require treatment in the next 2 years
  14. Females who are pregnant or lactating/breastfeeding
  15. Received a live virus vaccination within 28 days of first dose of rituximab
  16. Concurrent participation in a separate investigational therapeutic study
  17. Psychiatric illness/social situations that would interfere with study compliance

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04762160


Contacts
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Contact: Medical Affairs +1 (855) 500-1011 clinicaltrials@epizyme.com

Locations
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Sponsors and Collaborators
Epizyme, Inc.
Swedish Cancer Institute
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Responsible Party: Epizyme, Inc.
ClinicalTrials.gov Identifier: NCT04762160    
Obsolete Identifiers: NCT04590820
Other Study ID Numbers: EZH-1401
First Posted: February 21, 2021    Key Record Dates
Last Update Posted: April 1, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Lymphoma
Lymphoma, Follicular
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Rituximab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents