Follicular LymphomaPhase 1/2NCT05551936
A Study of Tazemetostat With Rituximab and Abbreviated Bendamustine in the Frontline Treatment of High Tumor Burden Follicular Lymphoma
A Phase 1/2 study testing Bendamustine, Rituximab and Tazemetostat in people with Follicular Lymphoma, run by Vaishalee Kenkre at 5 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Follicular Lymphoma
- What is being tested?
- Bendamustine, Rituximab and Tazemetostat
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 5 sitesUnited States
- Study dates
- 26 Jan 2023to May 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- --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)
- In addition to meeting GELF criteria, must have at least one FDG-avid site on PET that measures 1.5 cm in at least one dimension of a nodal site or 1cm in at least one dimension for extranodal sites.
- Received no prior therapy except local radiation therapy (field did not exceed 2 adjacent nodal regions), single agent rituximab (limited to 4 doses), or steroids for symptom control in the 28 days preceding trial enrollment.
- Must have prior EZH2 testing already performed or have tissue available to perform retrospective EZH2 testing. If prior EZH2 results are not available, tissue must be submitted. Tissue block is preferred but unstained slides are also acceptable. Patients who have insufficient or suboptimal tissue must be willing to have a biopsy performed prior to starting study drugs. See Correlative Lab Manual for details.
- Demonstrate adequate organ function as defined below; all screening labs to be obtained within 28 days prior to registration.
- Hematological
- Platelets ≥ 50 K/dL
- Absolute Neutrophil Count (ANC) ≥ 1000 K/mm3
- Hemoglobin (Hgb) ≥ 8 g/dL
- Renal
- Calculated creatinine clearance ≥ 40 mL/min using the Cockcroft-Gault formula
- or Serum creatinine < 2 mg/dL
- Hepatic
- Bilirubin ≤ 1.5 × upper limit of normal (ULN)
- Aspartate aminotransferase (AST) ≤ 3 × ULN
- Alanine aminotransferase (ALT) ≤ 3 × ULN
- Coagulation ---International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) ≤ 2 × ULN
- Females of childbearing potential with a male partner able to father a child must have a negative serum or urine pregnancy test within 7 days prior to registration. See the protocol for definition of childbearing potential.
- Females of childbearing potential must be willing to abstain from vaginal intercourse or use two effective methods of contraception from the time of informed consent, during the study and for 6 months after the last dose of study drug(s). Males able to father a child must be willing to abstain from vaginal intercourse or to use an effective method(s) of contraception from initiation of treatment, during the study and for 3 months after the last dose of study drug(s). See the protocol.
- As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Northwestern University
Chicago, Illinois, 60611
University of Illinois Cancer Center
Chicago, Illinois, 60612
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, 53705
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903
About this study
Official title: A Single Arm Phase I/II Study of Tazemetostat With Rituximab and Abbreviated Bendamustine in the Frontline Treatment of High Tumor Burden Follicular Lymphoma Big Ten Cancer Research Consortium BTCRC-LYM20-463
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
- Being tested
- Bendamustine, Rituximab, Tazemetostat
- Keywords
- follicular lymphoma, frontline, high tumor burden, EZH2
- Medical subject headings
- Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BendamustineDrug
Also called Bendeka, Treanda
90 mg/m^2 IV Days 1-2, Cycles 1-3
RituximabDrug
Also called Rituxan
375 mg/m^2 IV Day 1 Cycles 1-6
TazemetostatDrug
Also called Tazverik
RP2D (400, 600, or 800 mg) orally twice daily Cycles 1-6
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: Drug: Bendamustine; Drug: Rituximab; Drug: Tazemetostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 2 years
Secondary outcomes (3)
Overall Response Rate (ORR) after 3 cycles of BR + tazemetostat
Estimate the ORR after 3 cycles of BR plus tazemetostat. ORR (defined as CMR + PMR) as determined by the Lugano classification.
Measured: 2 years
Complete Metabolic Response (CMR) after 3 cycles BR + tazemetostat
Estimate the CMR rate after 3 cycles of BR plus tazemetostat. CMR rate will include complete metabolic response as defined by the Lugano classification.
Measured: 2 years
Duration of Response (DOR)
Evaluate DOR. DOR defined as the interval from response initiation (when either CMR or PMR is first determined) to progression or death, whichever occurs first. Metabolic response is defined by the Lugano classification.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2022
- Study start26 Jan 2023
- Primary completionMay 2026 (estimated)
- Study completionMay 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Follicular LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vaishalee Kenkre
- Sponsor type
- University, hospital or other
- Collaborators
- Epizyme, Inc., University of Wisconsin, Madison
- Responsible party
- Sponsor-investigator, Vaishalee Kenkre, Big Ten Cancer Research Consortium
- Investigators
- Vaishalee Kenkre, MD, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05551936
- Sponsor's protocol ID
- BTCRC LYM20-463
- Status last verified
- Feb 2026
- First submitted
- 19 Sep 2022
- Last updated
- 17 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Arm Phase I/II Study of Tazemetostat With Rituximab and Abbreviated Bendamustine in the Frontline Treatment of High Tumor Burden Follicular Lymphoma Big Ten Cancer Research Consortium BTCRC-LYM20-463
- ClinicalTrials.gov ID
- NCT05551936
- Acronym / sponsor ID
- BTCRC LYM20-463
- Conditions
- Follicular Lymphoma
- Keywords
- follicular lymphoma, frontline, high tumor burden, EZH2
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- Vaishalee KenkreUniversity, hospital or other
- Collaborators
- Epizyme, Inc., University of Wisconsin, Madison
- Study start
- 26 Jan 2023 (actual)
- Primary completion
- May 2026 (estimated)
- Study completion
- May 2027 (estimated)
- First posted
- 23 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Investigational Group | Experimental | Drug: Bendamustine, Drug: Rituximab, Drug: TazemetostatPhase 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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (34 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BendamustineAlso: Bendeka, Treanda90 mg/m^2 IV Days 1-2, Cycles 1-3 | Drug | Investigational Group |
| RituximabAlso: Rituxan375 mg/m^2 IV Day 1 Cycles 1-6 | Drug | Investigational Group |
| TazemetostatAlso: TazverikRP2D (400, 600, or 800 mg) orally twice daily Cycles 1-6 | Drug | Investigational Group |
Primary outcome
Phase I: Evaluate safety and tolerability of tazemetostat with bendamustine and rituximab (BR)
Time frame: 6 months
Toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 5.0).
Phase II: Complete metabolic response (CMR) with 3 cycles of BR + tazemetostat followed by 3 cycles of rituximab + tazemetostat
Time frame: 2 years
CMR will include complete metabolic response as defined by the Lugano classification.
3 secondary outcomes
Overall Response Rate (ORR) after 3 cycles of BR + tazemetostat
Time frame: 2 years
Complete Metabolic Response (CMR) after 3 cycles BR + tazemetostat
Time frame: 2 years
Duration of Response (DOR)
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vaishalee Kenkre, MD principal investigator
University of Wisconsin, Madison
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Bendamustine, Rituximab and Tazemetostat in people with Follicular Lymphoma, run by Vaishalee Kenkre at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 34 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 17 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase I: Evaluate safety and tolerability of tazemetostat with bendamustine and rituximab (BR) (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2026.