Follicular LymphomaPhase 2MandolinNCT06068881
A Study to Assess Efficacy and Safety of Oral Tazemetostat in Adult Participants With Relapsed/Refractory Follicular Lymphoma That Does Not Have an "EZH2 Gain-of-function" Genetic Mutation
A Phase 2 study testing Tazverik (Tazemetostat) in people with Follicular Lymphoma and Refractory Follicular Lymphoma, run by Epizyme, Inc..
Trial summary
The purpose of this research study is to learn about the effectiveness and safety of the study drug, tazemetostat, in adults with relapsed/refractory follicular lymphoma whose tumours do not have an "EZH2 gain-of-function" genetic mutation. Follicular lymphoma is a blood cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Follicular Lymphoma, Refractory Follicular Lymphoma
- What is being tested?
- Tazverik (Tazemetostat)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 2 Sep 2025to 6 Apr 2029
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- At least 18 years of age, inclusive, at the time of signing the informed consent form
- Histologically confirmed follicular lymphoma (FL) grades 1, 2, or 3A
- Previously treated with ≥1 prior systemic chemotherapy, immunotherapy, or chemo-immunotherapy consistent with those used in a US population, including but not limited to bendamustine, obinutuzumab, rituximab plus lenalidomide. Patients with only 1 prior line of therapy should not be eligible for available combination or monotherapies
- Documented relapsed, refractory, or progressive disease (PD) after treatment with systemic therapy (refractory defined as less than PR or as PD <6 months after last dose)
- Measurable disease as defined by Lugano Classification
- Have provided sufficient tumour tissue block or unstained slides for EZH2 mutation and copy number gain (CNG) testing
Show all 25Show fewer
- Wild-type EZH2 (ie, lacking GOF mutation). Note: If EZH2 GOF mutation status is known from site specific testing, WT patients can be enrolled with documentation of the testing, and additional archival tumour tissue or fresh lymph node biopsy taken before starting tazemetostat will be required for confirmatory testing of EZH2 GOF mutation status at study-specific laboratories. If EZH2 GOF mutation status is unknown, the results of central testing confirming wild-type (WT) EZH2 mutation status on an archival tumour sample, or a fresh lymph node biopsy is required before enrolment. (Archival tumour tissue collected within 15 months before the first dose is preferred, where feasible.)
- Eastern Cooperative Oncology Group (ECOG) performance status ≤2
- Adequate time between prior anticancer therapy and first dose of tazemetostat as follows:
- Cytotoxic chemotherapy: At least 21 days.
- Noncytotoxic chemotherapy (eg, small molecule inhibitor): At least 14 days.
- Monoclonal and/or bispecific antibodies or chimeric antigen receptor (CAR) T: At least 28 days.
- Radiotherapy: At least 6 weeks from prior radioisotope therapy; at least 12 weeks from 50% pelvic or total body irradiation.
- Adequate liver function, by all of the following criteria:
- Total bilirubin ≤1.5 × the upper limit of normal (ULN) except for unconjugated hyperbilirubinemia of Gilbert's syndrome.
- Alkaline phosphatase (ALP) (in the absence of bone disease), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤3 × ULN (≤5 × ULN if the patient has liver metastases).
- Adequate renal function: Calculated creatinine clearance ≥30 mL/minute per the Cockcroft and Gault formula
- Adequate bone marrow function, by all of the following criteria:
- Absolute neutrophil count (ANC) ≥1000/mm3 (≥1.0 × 109/L) if no lymphoma infiltration of bone marrow OR ANC ≥750/mm3 (≥0.75 × 109/L) with bone marrow infiltration: Without growth factor support (filgrastim or pegfilgrastim) for at least 14 days.
- Platelets ≥75,000/mm3 (≥75 × 109/L), evaluated at least 7 days after last platelet transfusion.
- Haemoglobin ≥9.0 g/dL, though may receive transfusion
- Adequate coagulation, by both of the following criteria (NOTE: In patients with thromboembolism risk, prophylactic anticoagulation, or antiplatelet therapy at investigator discretion, is recommended):
- International normalized ratio (INR) ≤1.5 × ULN
- Activated partial thromboplastin time (aPTT) ≤1.5 × ULN (unless on warfarin, then INR ≤3.0).
- Women of childbearing potential (WOCBP) must have 2 negative pregnancy tests (beta-human chorionic gonadotropin [β-hCG] on-site urine or serum tests with a minimum sensitivity of 25 mIU/mL or equivalent units of β-hCG) during screening. The second of these screening pregnancy tests
Who cannot join
- Grade 3b FL, mixed histology FL, or FL that has histologically transformed to DLBCL.
- Malignancies other than FL.
- Any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) or myeloproliferative neoplasm (MPN)
- Any prior history of T-cell lymphoblastic lymphoma (LBL)/T-cell acute lymphoblastic leukaemia (ALL)
- Major surgery within 4 weeks before the first dose of study intervention.
- Significant cardiovascular impairment.
Show all 15Show fewer
- Prolongation of corrected QT interval using Fridericia's formula (QTcF) to ≥480 msec at screening or history of long QT syndrome
- Venous thrombosis or pulmonary embolism within 3 months before starting tazemetostat. Note: Patients with deep vein thrombosis/pulmonary embolism greater than 3 months before treatment are eligible but recommended to receive prophylaxis
- Uncontrolled active infection requiring systemic therapy
- Active viral infection with human immunodeficiency virus (HIV)
- History of hepatitis B or C, unless they have adequate liver function as defined by inclusion criteria and are hepatitis B surface antigen negative with undetectable hepatitis B virus (HBV) DNA and/or have undetectable hepatitis C virus (HCV) ribonucleic acid (RNA) if HCV antibody positive
- History of solid organ transplant
- Prior exposure to tazemetostat or other inhibitor(s) of EZH2
- Taking medications that are known strong CYP3A inhibitors and strong or moderate CYP3A inducers (including St. John's wort)
- Pregnant or lactating/breastfeeding
About this study
Official title: A Phase 2, Open-label, Single-Arm Clinical Trial to Investigate the Efficacy and Safety of Oral Tazemetostat for the Treatment of Adult Participants Age 18 and Over With Relapsed/Refractory Follicular Lymphoma Lacking the EZH2 Gain-of-Function (GOF) Mutation
The purpose of this research study is to learn about the effectiveness and safety of the study drug, tazemetostat, in adults with relapsed/refractory follicular lymphoma whose tumours do not have an "EZH2 gain-of-function" genetic mutation. Follicular lymphoma is a blood cancer. It affects white blood cells called lymphocytes. White blood cells normally help to fight infections, but when you have follicular lymphoma, the blood cells can form tumours in your body. 'Relapsed/refractory' follicular lymphoma means the disease has either not improved or is getting worse (progressing) during or after previous treatment.
Tazemetostat already has approval in the United States for the treatment of adult patients with relapsed/refractory follicular lymphoma with or without the "EZH2" mutation who have no satisfactory alternative treatment options.
Read more
This study is being conducted to better understand the effectiveness in patients whose tumours do not have an "EZH2 gain-of-function" genetic mutation and who previously received therapies commonly used in the U.S. in your body.
'Relapsed/refractory' follicular lymphoma means the disease has either not improved or is getting worse (progressing) during or after previous treatment.
Tazemetostat already has approval in the United States for the treatment of adult patients with relapsed/refractory follicular lymphoma with or without the "EZH2 gain-of-function" mutation who have no satisfactory alternative treatment options. This study is being conducted to better understand the effectiveness in patients whose tumours do not have an "EZH2" genetic mutation and who previously received therapies commonly used in the U.S.
In this study, all participants will receive the study drug. It will be taken by mouth (orally), as a tablet, twice daily. The sizes and number of tumours according to scan results will be collected as well as results of safety tests (such as physical examinations and laboratory tests).
The study consists of 4 periods:
- Screening period may take up to 4 weeks and require at least 1 visit.
- Treatment period will require 2 visits for each of the first 2 months, followed by 1 visit every month for the remainder of the first 12 months, followed by 1 visit every 3 months (except for women of childbearing potential [WOCBP], who will continue to have a pregnancy testing every month) until unacceptable toxicity, disease progression, or the start of new systemic anticancer therapy, whichever is first.
- Safety follow-up period will last for 1 month after the last dose of tazemetostat, and it will end with 1 visit or telephone call.
- Long-term follow-up period is only for participants who stop taking tazemetostat while their disease continues to respond; this period will last until disease progression, start of new cancer treatment, or death from any cause, whichever is first, and will require a visit every 3 months.
Tazemetostat will be provided to participants who tolerate it for as long as their disease does not progress.
Participants may be transferred to another study or program after about 2 years for continued treatment with tazemetostat or for long-term follow-up. Patients may withdraw consent to participate at any time.
- Being tested
- Tazverik (Tazemetostat)
- Keywords
- EZH2 Gain-of-function, EZH2 GoF, Tazemetostat, Follicular Lymphoma
- Medical subject headings
- Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tazverik (Tazemetostat)Drug
Also called IPN60200
Oral Tablet
| Study group | Role | What they receive |
|---|---|---|
| Tazverik (Tazemetostat) | Experimental | 800mg tablet orally twice daily in continuous 28-day cycles Receives: Drug: Tazverik (Tazemetostat) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate (ORR) assessed by an independent review committee (IRC)
Defined as complete response + partial response [CR + PR]) in response-evaluable participants as assessed by a blinded independent review committee (BIRC).
Measured: From baseline to 4 months post last treatment (up to a maximum of 5 years)
Secondary outcomes (7)
ORR assessed by the Investigator
Measured: From baseline to 4 months post last treatment (up to a maximum of 5 years)
The Best Overall Response (BOR)
BOR as assessed by Investigator and by a BIRC.
Measured: From baseline to 4 months post last treatment (up to a maximum of 5 years)
Duration Of Response (DOR)
DOR in participants with an objective response (CR or PR), as assessed by Investigator and by an IRC.
Measured: From baseline to 4 months post last treatment (up to a maximum of 5 years)
Progression-free survival (PFS)
PFS from the date of the first dose of tazemetostat to the date of objective disease progression as assessed by Investigator and an IRC or to the death due to any cause, whichever occurs first.
Measured: From baseline to 4 months post last treatment (up to a maximum of 5 years)
Disease Control Rate (DCR)
DCR (CR + PR + Stable Disease (SD)) in response evaluable participants as assessed by Investigator and an IRC.
Measured: From baseline to 4 months post last treatment (up to a maximum of 5 years)
Percentage of participants who experience adverse events (AEs)
An Adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The clinical significance will be graded by the investigator.
Measured: From baseline to 4 months post last treatment (up to a maximum of 5 years)
Percentage of Participants with clinically significant changes in laboratory parameters.
Percentage of participants with clinically significant changes laboratory parameters (blood chemistry, hematology) will be reported. The clinical significance will be graded by the investigator.
Measured: From baseline to 4 months post last treatment (up to a maximum of 5 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2023
- Study start2 Sep 2025 (estimated)
- Primary completion6 Apr 2029 (estimated)
- Study completion6 Apr 2029 (estimated)
Why it stopped: Never started
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Epizyme, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Ipsen
- Responsible party
- Sponsor
- Investigators
- Ipsen Medical Director, Study director, Ipsen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06068881
- Sponsor's protocol ID
- CLIN-60200-452
- Other IDs
- 2023-508131-32-00, 2023
- Acronym
- Mandolin
- Status last verified
- Jan 2026
- First submitted
- 29 Sep 2023
- Last updated
- 30 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Open-label, Single-Arm Clinical Trial to Investigate the Efficacy and Safety of Oral Tazemetostat for the Treatment of Adult Participants Age 18 and Over With Relapsed/Refractory Follicular Lymphoma Lacking the EZH2 Gain-of-Function (GOF) Mutation
- ClinicalTrials.gov ID
- NCT06068881
- Acronym / sponsor ID
- Mandolin / CLIN-60200-452
- Keywords
- EZH2 Gain-of-function, EZH2 GoF, Tazemetostat, Follicular Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Never started
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Epizyme, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Ipsen
- Study start
- 2 Sep 2025 (estimated)
- Primary completion
- 6 Apr 2029 (estimated)
- Study completion
- 6 Apr 2029 (estimated)
- First posted
- 5 Oct 2023 (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.
The purpose of this research study is to learn about the effectiveness and safety of the study drug, tazemetostat, in adults with relapsed/refractory follicular lymphoma whose tumours do not have an "EZH2 gain-of-function" genetic mutation. Follicular lymphoma is a blood cancer. It affects white blood cells called lymphocytes. White blood cells normally help to fight infections, but when you have follicular lymphoma, the blood cells can form tumours in your body. 'Relapsed/refractory' follicular lymphoma means the disease has either not improved or is getting worse (progressing) during or after previous treatment.
Tazemetostat already has approval in the United States for the treatment of adult patients with relapsed/refractory follicular lymphoma with or without the "EZH2" mutation who have no satisfactory alternative treatment options.
This study is being conducted to better understand the effectiveness in patients whose tumours do not have an "EZH2 gain-of-function" genetic mutation and who previously received therapies commonly used in the U.S. in your body.
'Relapsed/refractory' follicular lymphoma means the disease has either not improved or is getting worse (progressing) during or after previous treatment.
Tazemetostat already has approval in the United States for the treatment of adult patients with relapsed/refractory follicular lymphoma with or without the "EZH2 gain-of-function" mutation who have no satisfactory alternative treatment options. This study is being conducted to better understand the effectiveness in patients whose tumours do not have an "EZH2" genetic mutation and who previously received therapies commonly used in the U.S.
In this study, all participants will receive the study drug. It will be taken by mouth (orally), as a tablet, twice daily. The sizes and number of tumours according to scan results will be collected as well as results of safety tests (such as physical examinations and laboratory tests).
The study consists of 4 periods:
- Screening period may take up to 4 weeks and require at least 1 visit.
- Treatment period will require 2 visits for each of the first 2 months, followed by 1 visit every month for the remainder of the first 12 months, followed by 1 visit every 3 months (except for women of childbearing potential [WOCBP], who will continue to have a pregnancy testing every month) until unacceptable toxicity, disease progression, or the start of new systemic anticancer therapy, whichever is first.
- Safety follow-up period will last for 1 month after the last dose of tazemetostat, and it will end with 1 visit or telephone call.
- Long-term follow-up period is only for participants who stop taking tazemetostat while their disease continues to respond; this period will last until disease progression, start of new cancer treatment, or death from any cause, whichever is first, and will require a visit every 3 months.
Tazemetostat will be provided to participants who tolerate it for as long as their disease does not progress.
Participants may be transferred to another study or program after about 2 years for continued treatment with tazemetostat or for long-term follow-up. Patients may withdraw consent to participate at any time.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tazverik (Tazemetostat) | Experimental | Drug: Tazverik (Tazemetostat)800mg tablet orally twice daily in continuous 28-day cycles |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- At least 18 years of age, inclusive, at the time of signing the informed consent form
- Histologically confirmed follicular lymphoma (FL) grades 1, 2, or 3A
- Previously treated with ≥1 prior systemic chemotherapy, immunotherapy, or chemo-immunotherapy consistent with those used in a US population, including but not limited to bendamustine, obinutuzumab, rituximab plus lenalidomide. Patients with only 1 prior line of therapy should not be eligible for available combination or monotherapies
- Documented relapsed, refractory, or progressive disease (PD) after treatment with systemic therapy (refractory defined as less than PR or as PD <6 months after last dose)
- Wild-type EZH2 (ie, lacking GOF mutation). Note: If EZH2 GOF mutation status is known from site specific testing, WT patients can be enrolled with documentation of the testing, and additional archival tumour tissue or fresh lymph node biopsy taken before starting tazemetostat will be required for confirmatory testing of EZH2 GOF mutation status at study-specific laboratories. If EZH2 GOF mutation status is unknown, the results of central testing confirming wild-type (WT) EZH2 mutation status on an archival tumour sample, or a fresh lymph node biopsy is required before enrolment. (Archival tumour tissue collected within 15 months before the first dose is preferred, where feasible.)
Key exclusion criteria (15 listed)
- Grade 3b FL, mixed histology FL, or FL that has histologically transformed to DLBCL.
- Malignancies other than FL.
- Any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) or myeloproliferative neoplasm (MPN)
- Any prior history of T-cell lymphoblastic lymphoma (LBL)/T-cell acute lymphoblastic leukaemia (ALL)
- Major surgery within 4 weeks before the first dose of study intervention.
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 |
|---|---|---|
| Tazverik (Tazemetostat)Also: IPN60200Oral Tablet | Drug | Tazverik (Tazemetostat) |
Primary outcome
Objective response rate (ORR) assessed by an independent review committee (IRC)
Time frame: From baseline to 4 months post last treatment (up to a maximum of 5 years)
Defined as complete response + partial response [CR + PR]) in response-evaluable participants as assessed by a blinded independent review committee (BIRC).
7 secondary outcomes
ORR assessed by the Investigator
Time frame: From baseline to 4 months post last treatment (up to a maximum of 5 years)
The Best Overall Response (BOR)
Time frame: From baseline to 4 months post last treatment (up to a maximum of 5 years)
Duration Of Response (DOR)
Time frame: From baseline to 4 months post last treatment (up to a maximum of 5 years)
Progression-free survival (PFS)
Time frame: From baseline to 4 months post last treatment (up to a maximum of 5 years)
Disease Control Rate (DCR)
Time frame: From baseline to 4 months post last treatment (up to a maximum of 5 years)
Percentage of participants who experience adverse events (AEs)
Time frame: From baseline to 4 months post last treatment (up to a maximum of 5 years)
Percentage of Participants with clinically significant changes in laboratory parameters.
Time frame: From baseline to 4 months post last treatment (up to a maximum of 5 years)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2026.
Related trials for Follicular Lymphoma
RecruitingPhase 1/2
A Platform Trial Evaluating New Drugs or Combination in R/R Peripheral T-cell Lymphomas
Peripheral T Cells Lymphoma (PTCL), Follicular Helper T-Cell Lymphoma
Active, not recruiting
EXHIT ENTRE Implementation Trial of High Intensity Versus Low Intensity Strategy
Substance Use Disorders, Opioid Use Disorder, Severe
RecruitingPhase 1/2
Dose Escalation and Dose Expansion Study of MDX2003 in Patients With Different Types of Lymphoma
Lymphoma, Waldenström Macroglobulinemia (WM)
Active, not recruitingPhase 1
A Rollover Study of CC-122
Non-Hodgkin Lymphoma
Recruiting
STEpwise Research Program to Promote INGeniouS ONline Supportive Solutions in the Relief of Cancer-related Fatigue
Cancer Diagnosis, Moderate or Severe Score of Cancer-related Fatigue (CRF)
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.
Ipsen Medical Director study director
Ipsen
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tazverik (Tazemetostat) in people with Follicular Lymphoma and Refractory Follicular Lymphoma, run by Epizyme, Inc..
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 25 inclusion and 15 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: withdrawn, as of the sponsor's last update on 30 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
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 phase mean?
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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Objective response rate (ORR) assessed by an independent review committee (IRC) (time frame: From baseline to 4 months post last treatment (up to a maximum of 5 years)). 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 30 Jan 2026.