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

NCT04762160 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: EZH-1401
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 20

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.

Conditions

Follicular Lymphoma

Keywords

follicular lymphoma; relapse follicular lymphoma; refractory follicular lymphoma; rituximab; tazemetostat

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (4)

• Progression Free Survival (PFS)

  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

• Duration of Response (DOR)

  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

• ORR in a Subset of Participants With MT EZH2

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

• ORR in Rituximab Refractory Participants

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

Study Arms (1)

Tazmetostat in combination with rituximab

EXPERIMENTAL

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; Combination Product: Rituximab

Interventions

Tazemetostat DRUG

Study Drug

Also known as: EPZ-6438

Tazmetostat in combination with rituximab

Rituximab COMBINATION_PRODUCT

Partner Drug

Also known as: Rituximab Hyaluronidase

Tazmetostat in combination with rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Epizyme, Inc.: lead
• Swedish Cancer Institute: collaborator

Study Sites (20)

Alabama Oncology

Birmingham, Alabama, 35223, United States

Location

Compassionate Cancer Care

Fountain Valley, California, 92708, United States

Location

USOR/Rocky Mountain Cancer Centers

Boulder, Colorado, 80303, United States

Location

USOR/ Illinois Cancer Specialists

Niles, Illinois, 60714, United States

Location

XCancer/ Northwest Oncology & Hematology

Rolling Meadows, Illinois, 60008, United States

Location

Revive/Oakland Medical Group

Farmington Hills, Michigan, 48336, United States

Location

Revive/Hematology Oncology Associates of Rockland

Sterling Heights, Michigan, 48314, United States

Location

USOR/ NY Oncology Hematology

Albany, New York, 12206, United States

Location

East Carolina University

Greenville, North Carolina, 27858, United States

Location

USOR/ Oncology & Hematology Care Clinical Trials

Cincinnati, Ohio, 45236, United States

Location

XCancer/Dayton Physicians Network

Kettering, Ohio, 45409, United States

Location

XCancer/Tennessee Cancer Specialists

Knoxville, Tennessee, 37909, United States

Location

USOR/ Texas Oncology

Austin, Texas, 78705, United States

Location

USOR/Texas Oncology

Dallas, Texas, 75230, United States

Location

USOR/ Texas Oncology

San Antonio, Texas, 78240, United States

Location

USOR/ Texas Oncology

Tyler, Texas, 75702, United States

Location

USOR/Texas Oncology

Weslaco, Texas, 78596, United States

Location

USOR/Virginia Cancer Specialists

Gainesville, Virginia, 20155, United States

Location

USOR/Oncology & Hematology Associates of Southwest Virginia

Roanoke, Virginia, 24014, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

tazemetostat; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

The study was terminated early due to business reasons prior to enrolling the target number of participants needed to achieve target power and was insufficient to produce statistically reliable results and was not due to any safety concerns. No summary statistics are available given the limited data from the small number of evaluable participants and individual participant data are also not presented to protect the privacy of the individuals.

Results Point of Contact

• Title: Medical Director
• Organization: Ipsen

clinical.trials@ipsen.com

see email

Study Officials

• Ipsen Medical Director

  Ipsen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2021
• First Posted: February 21, 2021
• Study Start: December 15, 2020
• Primary Completion: March 22, 2022
• Study Completion: March 22, 2022
• Last Updated: March 25, 2024
• Results First Posted: November 21, 2023

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (20)