Status:
TERMINATED
SYMPHONY-2, A Trial to Examine Combination of Tazemetostat With Rituximab in Subjects With Relapsed/Refractory Follicular Lymphoma
Lead Sponsor:
Epizyme, Inc.
Collaborating Sponsors:
Swedish Cancer Institute
Conditions:
Follicular Lymphoma
Eligibility:
All Genders
18+ years
Phase:
PHASE2
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 regimen...
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 ev...
Eligibility Criteria
Inclusion
- 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
- 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.
Exclusion
- 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)
- 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
Key Trial Info
Start Date :
December 15 2020
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
March 22 2022
Estimated Enrollment :
5 Patients enrolled
Trial Details
Trial ID
NCT04762160
Start Date
December 15 2020
End Date
March 22 2022
Last Update
March 25 2024
Active Locations (20)
Enter a location and click search to find clinical trials sorted by distance.
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