A Study of Tazemetostat With Rituximab and Abbreviated Bendamustine in the Frontline Treatment of High Tumor Burden Follicular Lymphoma

NCT05551936 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: BTCRC LYM20-463
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 5

Brief Summary

This study is planned as a single arm clinical trial of tazemetostat in combination with bendamustine and rituximab with both a phase I and phase II component. All patients will receive tazemetostat twice daily on days 1-28 in combination with bendamustine 90 mg/m2 IV on days 1 and 2 and rituximab 375 mg/m2 IV on day 1 of a 28-day cycle for up to three cycles. Following this, patients will receive tazemetostat twice daily on days 1-28 and rituximab 375 mg/m2 IV on day 1 of a 28-day cycle for up to three cycles.

Conditions

Follicular Lymphoma

Keywords

follicular lymphoma; frontline; high tumor burden; EZH2

Outcome Measures

Primary Outcomes (2)

• Phase I: Evaluate safety and tolerability of tazemetostat with bendamustine and rituximab (BR)

  Toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 5.0).

  6 months

• Phase II: Complete metabolic response (CMR) with 3 cycles of BR + tazemetostat followed by 3 cycles of rituximab + tazemetostat

  CMR will include complete metabolic response as defined by the Lugano classification.

  2 years

Secondary Outcomes (3)

• Overall Response Rate (ORR) after 3 cycles of BR + tazemetostat

  2 years

• Complete Metabolic Response (CMR) after 3 cycles BR + tazemetostat

  2 years

• Duration of Response (DOR)

  2 years

Study Arms (1)

Investigational Group

EXPERIMENTAL

Phase 1: 90 mg/m\^2 of bendamustine by IV on Day 1 and 2 of a 28 day cycle (up to 3 Cycles) 375 mg/m\^2 of rituximab by IV on Day 1 of a 28 day cycle (up to 3 Cycles) Participants enrolled in this phase will be given one of 3 different dose levels of tazemetostat along with the drugs above (for up to 3 Cycles). 3 patients will be assigned to the lowest dose level and if the dose is tolerated, 3 more patients will be enrolled one dose level higher. Up to 18 participants being enrolled. Dose Level 1: 400 mg of tazemetostat orally twice daily Dose Level 2: 600 mg of tazemetostat orally twice daily Dose Level 3: 800 mg of tazemetostat orally twice daily Phase 2: 6 patients from Phase 1 who were treated at the recommended Phase 2 dose will be added to 21 additional patients. 375 mg/m\^2 of rituximab through IV on Day 1 of a 28 day cycle (Cycles 1-6) Tazemetostat orally twice daily of a 28 day cycle (Cycles 1-6)

Drug: Bendamustine; Drug: Rituximab; Drug: Tazemetostat

Interventions

Bendamustine DRUG

90 mg/m\^2 IV Days 1-2, Cycles 1-3

Also known as: Bendeka, Treanda

Investigational Group

Rituximab DRUG

375 mg/m\^2 IV Day 1 Cycles 1-6

Also known as: Rituxan

Investigational Group

Tazemetostat DRUG

RP2D (400, 600, or 800 mg) orally twice daily Cycles 1-6

Also known as: Tazverik

Investigational Group

Eligibility Criteria

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

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0-2 within 10 days prior to registration.
• Low grade follicular lymphoma (grade 1-2 or 3A by WHO-HAEM4R and/or cFL by WHO-HAEM5). Specifically, grade 3B or FLBL will not be allowed. Must not have evidence of transformed lymphoma at the time of study enrollment.
• Stage II, III, or IV by Ann Arbor staging system.
• Meet the definition of high tumor burden follicular lymphoma as defined by Groupe d'Etude des Lymphomes Follicularies (GELF) Criteria or be defined as high risk by the follicular lymphoma international prognostic index (FLIPI) 1 or FLIPI 2.
• GELF Criteria (Must meet ≥ 1 of the following)
• Any nodal or extranodal mass ≥ 7 cm in diameter
• Involvement of ≥ 3 nodal sites ≥ 3 cm
• Systemic or B symptoms
• Presence of serous effusion
• Splenic enlargement
• Risk of compression syndrome (epidural, ureteral, etc)
• Leukemic phase of disease
• Cytopenia deemed due to disease involvement (hemoglobin \< 10, granulocyte count \< 1.5×10\^9/L, or platelet count \< 100×10\^9/L)

You may not qualify if:

• Active infection requiring systemic therapy with 4 weeks of study drug administration.
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
• Concurrent malignancy or malignancy within the last 3 years (except for ductal breast cancer in situ, non-melanoma skin cancer, prostate cancer not requiring treatment, and cervical carcinoma in situ) whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are not eligible for this trial. Any prior history of myeloid malignancies are excluded, regardless of when the subject was diagnosed, including myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), myeloproliferative neoplasm (MPN), prior history of T-cell lymphoblastic lymphoma (T-LBL), T-cell acute lymphoblastic leukemia (T-ALL), or B-cell acute lymphoblastic leukemia (B-ALL).
• Active central nervous system (CNS) metastases or leptomeningeal disease. NOTE: Subjects who are symptomatic and have not undergone prior brain imaging must undergo a head computed tomography (CT) scan or brain MRI within 28 days prior to registration to exclude brain metastases.
• Treatment with any investigational drug within 4 weeks prior to registration.
• Subjects who require chronic use of moderate or strong CYP3A4/5 inhibitors or inducers within 28 days prior to registration.
• Clinically significant acute infection requiring systemic antibacterial, antifungal, or antiviral therapy.
• Known Uncontrolled Human Immunodeficiency Virus infection. Testing not required. NOTE: If a subject is known to have HIV/AIDS, then they will be allowed on study with adequate antiviral therapy, no detectable viral load, and stable on antiviral treatment for ≥ 4 weeks prior to first dose of study drug(s).
• Known hepatitis C infection. Testing not required. NOTE: If hepatitis C antibody test is known positive, patients are excluded unless a hepatitis C virus ribonucleic acid (HCV RNA) is negative.
• Must be tested for hepatitis B within 28 days of registration: including hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B core antibody. A positive hepatitis B core antibody should be followed by hepatitis B DNA PCR testing to confirm or rule out active infection. Patients with hepatitis B surface antigen and/or detectable hepatitis B DNA PCR are not allowed on study. Patients with a positive hepatitis B core antibody but negative hepatitis B surface antigen and hepatitis B DNA PCR will be allowed on study, but hepatitis B prophylactic treatment should be strongly considered.
• Clinically significant cardiovascular disease or cardiac insufficiency (New York Heart Association classes III-IV), cardiomyopathy, preexisting clinically significant arrhythmia, acute myocardial infarction within 3 months of enrollment, angina pectoris within 3 months of enrollment.

Sponsors & Collaborators

• Vaishalee Kenkre: lead
• Epizyme, Inc.: collaborator
• University of Wisconsin, Madison: collaborator

Study Sites (5)

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Illinois Cancer Center

Chicago, Illinois, 60612, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53705, United States

Location

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

Bendamustine Hydrochloride; Rituximab; tazemetostat

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)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Vaishalee Kenkre, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: September 19, 2022
• First Posted: September 23, 2022
• Study Start: January 26, 2023
• Primary Completion: May 1, 2026
• Study Completion (Estimated): May 1, 2027
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)