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

Follicular Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04762160
• Other study ID #: EZH-1401
• Status: Terminated
• Phase: Phase 2
• Start date: December 15, 2020
• Est. completion date: March 22, 2022

Study information

• Verified date: March 2024
• Source: Ipsen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT04590820

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: March 22, 2022
• Est. primary completion date: March 22, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 [ß-hCG] test with a minimum sensitivity of 25 mIU/mL or equivalent units of ß-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

Related Conditions & MeSH terms

• Follicular Lymphoma
• Lymphoma
• Lymphoma, Follicular

Intervention

Drug:
• Tazemetostat
Study Drug

Combination Product:
• Rituximab
Partner Drug

Locations

Country	Name	City	State
United States	USOR/ NY Oncology Hematology	Albany	New York
United States	USOR/ Texas Oncology	Austin	Texas
United States	Alabama Oncology	Birmingham	Alabama
United States	USOR/Rocky Mountain Cancer Centers	Boulder	Colorado
United States	USOR/ Oncology & Hematology Care Clinical Trials	Cincinnati	Ohio
United States	USOR/Texas Oncology	Dallas	Texas
United States	Revive/Oakland Medical Group	Farmington Hills	Michigan
United States	Compassionate Cancer Care	Fountain Valley	California
United States	USOR/Virginia Cancer Specialists	Gainesville	Virginia
United States	East Carolina University	Greenville	North Carolina
United States	XCancer/Dayton Physicians Network	Kettering	Ohio
United States	XCancer/Tennessee Cancer Specialists	Knoxville	Tennessee
United States	USOR/ Illinois Cancer Specialists	Niles	Illinois
United States	USOR/Oncology & Hematology Associates of Southwest Virginia	Roanoke	Virginia
United States	XCancer/ Northwest Oncology & Hematology	Rolling Meadows	Illinois
United States	USOR/ Texas Oncology	San Antonio	Texas
United States	Swedish Cancer Institute	Seattle	Washington
United States	Revive/Hematology Oncology Associates of Rockland	Sterling Heights	Michigan
United States	USOR/ Texas Oncology	Tyler	Texas
United States	USOR/Texas Oncology	Weslaco	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Epizyme, Inc.	Swedish Cancer Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Progression Free Survival (PFS)	PFS was defined as the time from first dose of study drug to the time of the earliest date of CR or PR per the 2014 Lugano Classification or death, whichever occurred first, as assessed by an IRC. CR= complete metabolic response per 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 from first dose of study drug to earliest date of disease progression or death as assessed up to 24 months by an IRC
Secondary	Duration of Response (DOR)	DOR was defined as the time from the earliest date of CR or PR per the 2014 Lugano Classification to documented progression or death, whichever comes first, as assessed by an IRC. CR= complete metabolic response per 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 from earliest date of CR or PR to documented progression or death as assessed up to 24 months by an IRC
Secondary	ORR in a Subset of Participants With MT EZH2	ORR was assessed according to 2014 Lugano Classification, in the pooled group regardless of mutation status and in a subset of participants with MT EZH2.	Planned to be assessed at the following timepoints: Cycles 3, 6, 12, 18, and 24
Secondary	ORR in Rituximab Refractory Participants	ORR was assessed according to 2014 Lugano Classification, in rituximab refractory participants.	Planned to be assessed at the following timepoints: Cycle 3, Cycle 6, Cycle 12, Cycle 18, and Cycle 24.