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

NCT ID: NCT04762160

Last Updated: 2024-03-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-15
• Study Completion Date: 2022-03-22

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.

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.

Conditions

Follicular Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Tazemetostat

Intervention Type: DRUG

Study Drug

Rituximab

Intervention Type: COMBINATION_PRODUCT

Partner Drug

Interventions

Tazemetostat

Study Drug

Intervention Type: DRUG

Rituximab

Partner Drug

Intervention Type: COMBINATION_PRODUCT

Other Intervention Names

EPZ-6438; Rituximab Hyaluronidase

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Swedish Cancer Institute

OTHER

Sponsor Role: collaborator

Epizyme, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ipsen Medical Director

Role: STUDY_DIRECTOR

Ipsen

Locations

Alabama Oncology

Birmingham, Alabama, United States

Compassionate Cancer Care

Fountain Valley, California, United States

USOR/Rocky Mountain Cancer Centers

Boulder, Colorado, United States

USOR/ Illinois Cancer Specialists

Niles, Illinois, United States

XCancer/ Northwest Oncology & Hematology

Rolling Meadows, Illinois, United States

Revive/Oakland Medical Group

Farmington Hills, Michigan, United States

Revive/Hematology Oncology Associates of Rockland

Sterling Heights, Michigan, United States

USOR/ NY Oncology Hematology

Albany, New York, United States

East Carolina University

Greenville, North Carolina, United States

USOR/ Oncology & Hematology Care Clinical Trials

Cincinnati, Ohio, United States

XCancer/Dayton Physicians Network

Kettering, Ohio, United States

XCancer/Tennessee Cancer Specialists

Knoxville, Tennessee, United States

USOR/ Texas Oncology

Austin, Texas, United States

USOR/Texas Oncology

Dallas, Texas, United States

USOR/ Texas Oncology

San Antonio, Texas, United States

USOR/ Texas Oncology

Tyler, Texas, United States

USOR/Texas Oncology

Weslaco, Texas, United States

USOR/Virginia Cancer Specialists

Gainesville, Virginia, United States

USOR/Oncology & Hematology Associates of Southwest Virginia

Roanoke, Virginia, United States

Swedish Cancer Institute

Seattle, Washington, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

EZH-1401

Identifier Type: -

Identifier Source: org_study_id

NCT04590820

Identifier Type: -

Identifier Source: nct_alias