Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

SYMPHONY-2, A Trial to Examine Combination of Tazemetostat and Rituximab for Patients With Relapsed/Refractory Follicular Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04762160
Recruitment Status : Recruiting
First Posted : February 21, 2021
Last Update Posted : September 24, 2021
Sponsor:
Collaborator:
Swedish Cancer Institute
Information provided by (Responsible Party):
Epizyme, Inc.

Brief Summary:
The goal of this study is to examine the feasibility and efficacy of adding the EZH2 inhibitor, tazemetostat, to rituximab, standard second line or beyond therapy as a means to improve disease response.

Condition or disease Intervention/treatment Phase
Follicular Lymphoma Drug: Tazemetostat 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 prior systemic lines of therapy for FL, and features early futility stopping to maintain subject safety.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 59 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model 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 prior systemic lines of therapy for FL, and features early futility stopping rules.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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 is supplied by Epizyme in pre-counted, appropriately labeled bottles. Tazemetostat will be administered from C1D1 to the end of Cycle 24, for a total of 24 months of therapy. Rituximab will be administered by either subcutaneous injection or IV infusion according to the regional product prescribing information and labeling. 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. Rituximab will be procured by the clinical sites from commercial sources. Disease Assessments will be performed at screening, C3D1, C6D1, C12D1, C18D1, C24D1
Drug: Tazemetostat
Tazmetostat in combination with rituximab
Other Names:
  • rituximab
  • Rituxan




Primary Outcome Measures :
  1. Change in Objective Response Rate (ORR) [ Time Frame: Screening ]
    To assess the objective response rate (ORR; complete response + partial response [CR + PR]) of Tazemetostat in combination with Rituximab in patients with relapsed/refractory follicular lymphoma and without EZH2 mutation status

  2. Change in Objective Response Rate (ORR) [ Time Frame: Day 1 of Cycle 3 (each cycle is 28 days). ]
    To assess the objective response rate (ORR; complete response + partial response [CR + PR]) of Tazemetostat in combination with Rituximab in patients with relapsed/refractory follicular lymphoma and without EZH2 mutation status

  3. Change in Objective Response Rate (ORR) [ Time Frame: Day 1 of Cycle 6 (each cycle is 28 days). ]
    To assess the objective response rate (ORR; complete response + partial response [CR + PR]) of Tazemetostat in combination with Rituximab in patients with relapsed/refractory follicular lymphoma and without EZH2 mutation status

  4. Change in Objective Response Rate (ORR) [ Time Frame: Day 1 of Cycle 12 (each cycle is 28 days). ]
    To assess the objective response rate (ORR; complete response + partial response [CR + PR]) of Tazemetostat in combination with Rituximab in patients with relapsed/refractory follicular lymphoma and without EZH2 mutation status

  5. Change in Objective Response Rate (ORR) [ Time Frame: Day 1 of Cycle 18 (each cycle is 28 days). ]
    To assess the objective response rate (ORR; complete response + partial response [CR + PR]) of Tazemetostat in combination with Rituximab in patients with relapsed/refractory follicular lymphoma and without EZH2 mutation status

  6. Change in Objective Response Rate (ORR) [ Time Frame: Day 1 of Cycle 24 (each cycle is 28 days). ]
    To assess the objective response rate (ORR; complete response + partial response [CR + PR]) of Tazemetostat in combination with Rituximab in patients with relapsed/refractory follicular lymphoma and without EZH2 mutation status


Secondary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events [ Time Frame: Adverse events will be collected beginning at screening and then at all subsequent time points up to 4 years ]
    To evaluate safety of the combination ofTazemetostat and Rituxanby assessingincidence of adverse events/serious adverse events, change of vital signs, lab results, and physical exam findings from baseline. This will be measured in accordance to National Cancer (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.00

  2. Progression Free Survival [ Time Frame: 2 years ]
    To estimate the median progression-free survival (PFS) of tazemetostat in combination with rituximab at 2 years in R/R follicular lymphoma with wild type mutation status, and in the pooled group regardless of mutation status.



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.


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

Inclusion Criteria:

  1. Have histologically confirmed FL, grades 1 to 3a. Subjects may have relapsed/refractory disease following at least 2 standard prior systemic treatment regimens where at least an anti-CD20-based regimen was used.
  2. Eastern Cooperative Oncology Group (ECOG) score of 0 </= 2
  3. Treatment recommended in accordance with the GELF criteria due to the presence of at least one of the following:

    1. Any nodal or extranodal tumor mass >7 cm diameter
    2. Involvement of at least 3 nodal sites, each with diameter >3 cm
    3. Presence of any systemic or B symptoms
    4. Splenic enlargement with inferior margin below the umbilical line
    5. Compression syndrome (ureteral, orbital, gastrointestinal)
    6. Pleural or peritoneal serous effusion (irrespective of cell content)
    7. Leukemic phase (>5.0 x 109/L circulating malignant cells)
    8. Cytopenias (granulocyte count <1.0 x 109/L and/or platelets <100 x 109/L)
  4. Meet the following laboratory parameters:

    1. 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. Serum AST and ALT/SGPT ≤ 3.0 x ULN, unless related to disease involvement
    4. Total bilirubin ≤ 1.5 x ULN, unless due to disease involvement, Gilbert's, or hemolytic anemia).
    5. Estimated creatinine clearance (ie, eGFR using Cockcroft-Gault) ≥ 40 mL/min.
  5. No prior therapy with EZH2 inhibitors
  6. At least one bi-dimensionally measurable nodal lesion > 1.5 cm in its longest diameter by CT scan or MRI excluding lesions that meet the following criteria

    1. Previously irradiated lesions should not be counted as target lesions
    2. Lesions that are intended to be used to collect tissue samples for biopsy should not be counted as target lesions
    3. Bone lesions should not be counted as target lesions
  7. All clinically significant treatment-related toxicity from prior therapy, except for alopecia, resolved to ≤ Grade 1 or to a new stable baseline
  8. Female subjects of reproductive potential must have a negative urine/serum/pregnancy test upon study entry. Female subjects who are of non-reproductive potential (i.e., post-menopausal by history - no menses for ≥1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy) are exempt from pregnancy testing.
  9. Male and female subjects of reproductive potential who agree to use both a highly effective method of birth control (eg, implants, injectables, combined oral contraceptives, some intrauterine devices [IUDs], complete abstinence1, or sterilized partner) and a barrier method (eg, condoms, cervical ring, sponge, etc) during the period of therapy and for 12 months after the last dose of rituximab.
  10. Men and women must agree to refrain from sperm or oocyte donation during the study and for 12 months after the last dose of rituximab.

Exclusion Criteria:

  1. Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia
  2. Transformed Follicular lymphoma
  3. Any uncontrolled illness including, but not limited to, significant active infections, hypertension, angina, arrhythmias, pulmonary disease, or autoimmune dysfunction
  4. Subjects who have tested positive for hepatitis B surface antigen and/or hepatitis B core antibody plus have a hepatitis B polymerase chain reaction (PCR) assay (subjects with a negative PCR assay are permitted with appropriate anti-viral prophylaxis)
  5. Positive for hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) antibody; subjects with positive hepatitis C antibody are eligible if they are negative for hepatitis C virus by PCR
  6. Other diagnosis of cancer that is likely to require treatment in the next 2 years, with the exception of the following:

    1. Curatively treated basal cell carcinoma or squamous cell carcinoma of the skin
    2. Curatively treated carcinoma in situ of the cervix
    3. Hormonal therapy for prostate cancer
  7. History of clinically significant cardiovascular abnormalities such as congestive heart failure (New York Heart Association classification ≥ 2), myocardial infarction within 6 months of study entry
  8. History of clinically significant gastrointestinal (GI) conditions, particularly:

    1. Known GI condition that would interfere with swallowing or the oral absorption or tolerance of study drug
    2. Pre-existing malabsorption syndrome or other clinical situation that would affect oral absorption
  9. Females who are currently breastfeeding
  10. Received a live virus vaccination within 28 days of first dose of Rituxan
  11. Participation in a separate investigational therapeutic study
  12. 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
Layout table for location contacts
Contact: Heather O'Connor, MD 617-300-0273 clinicaltrials@epizyme.com
Contact: Deyaa Adib, MD 908-246-2899 dadib@epizyme.com

Locations
Layout table for location information
United States, Alabama
Alabama Oncology Recruiting
Birmingham, Alabama, United States, 35223
Contact: Kailee Hawkins       kailee.hawkins@alabamaoncology.com   
Principal Investigator: Katisha Vance, MD         
United States, Illinois
XCancer/ Northwest Oncology & Hematology Recruiting
Rolling Meadows, Illinois, United States, 60008
Contact: Nowsheen Azeemuddin       nowsheena@northwestoncology.com   
Principal Investigator: Bruce Bank, MD         
United States, Michigan
Revive/Oakland Medical Group Recruiting
Farmington Hills, Michigan, United States, 48336
Contact: Mazhar Jaffry       mazharjaffry@yahoo.com   
Principal Investigator: Savitha Balaraman, MD         
Revive/Hematology Oncology Associates of Rockland Not yet recruiting
Sterling Heights, Michigan, United States, 48314
Contact: Kristi Simcox       kristi.simcox@biomed-research.com   
Principal Investigator: Adil Akhtar, MD         
United States, North Carolina
East Carolina University Not yet recruiting
Greenville, North Carolina, United States, 27858
Contact: Czarina Stroud       cowoc18@ecu.edu   
Principal Investigator: Darla Liles, MD         
United States, Ohio
XCancer/Dayton Physicians Network Recruiting
Kettering, Ohio, United States, 45409
Contact: Katherine G Williams       kwilliams@daytonphysicians.com   
Principal Investigator: Kelly Lynn Robbins Miller, MD, PHD         
United States, Tennessee
XCancer/Tennessee Cancer Specialists Recruiting
Knoxville, Tennessee, United States, 37909
Contact: Kristi Simcox    865-934-2672    kristi.simcox@biomed-research.com   
Principal Investigator: Richard T Lee, MD         
United States, Washington
Swedish Cancer Institute Recruiting
Seattle, Washington, United States, 898104
Contact: Neil Bailey       Neil.Bailey@swedish.org   
Principal Investigator: Krish Patel, MD         
Sponsors and Collaborators
Epizyme, Inc.
Swedish Cancer Institute
Layout table for additonal information
Responsible Party: Epizyme, Inc.
ClinicalTrials.gov Identifier: NCT04762160    
Other Study ID Numbers: EZH-1401
First Posted: February 21, 2021    Key Record Dates
Last Update Posted: September 24, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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:
Layout table for MeSH terms
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