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A Study to Assess the Efficacy, Safety, Pharmacodynamics, and Pharmacokinetics of Tazemetostat in Combination With Lenalidomide Plus Rituximab Versus Placebo in Combination With Lenalidomide Plus Rituximab in Adult Patients at Least 18 Years of Age With Relapsed/Refractory Follicular Lymphoma.

PHASE3RECRUITING

The participants of this study would have relapsed/refractory follicular lymphoma. Follicular lymphoma is a type of blood cancer. It is referred to as 'relapsed' when the disease has come back after a period of improvement after that follows a treatment regimen and 'refractory' when treatment no longer works.

Stage 1 of this trial will study the safety and the level that adverse effects of each of the study drug combinations can be tolerated (known as tolerability). It is also designed to establish a recommended study drug dosage for stage 2 and 3. Stage 1 of the study is completed.

Stages 2 and 3 will evaluate and compare how long participants live without their disease getting worse when receiving the study drug in combination with other drug treatment versus the placebo (dummy drug) in combination with other drug treatment.

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Study details:

Stage 1 is a safety run-in phase, was designed to evaluate the safety of the combination of tazemetostat and R2, as well as to establish the RP3D for Stage 2, which is now completed. Stage 2 is an efficacy and safety phase for an assessment of the FL population with the enhancer of zeste homolog 2 (EZH2) gain-of-function (GOF) mutation (EZH2 mutant-type \[MT\]) and without the EZH2 GOF mutation (EZH2 wild-type \[WT\]). In Stage 2, EZH2 WT and EZH2 MT patients will be randomly assigned in a 1:1 ratio to tazemetostat + R2 or placebo + R2.

There will be 1 futility interim analysis (IA) and 1 efficacy IA for WT population and 1 efficacy IA for MT population. Stage 3 is a long-term follow-up of patients for assessment of response and overall survival. All patients will be followed for survival until 5 years post last patient enrolled in the study.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

Have voluntarily agreed to provide written informed consent and demonstrated willingness and ability to comply with all aspects of the protocol.

Males or females are ≥18 years of age at the time of providing voluntary written informed consent.

Life expectancy ≥3 months before enrollment.

Meet requirement for hepatitis and human immunodeficiency virus (HIV) infection as follows: Negative serologic or polymerase chain reaction (PCR) test results for acute or chronic hepatitis B virus (HBV) infection Note: Participants whose HBV infection status could not be determined by serologic test results have to be negative for HBV-DNA by PCR to be eligible for study participation. Participants seropositive for HBV with undetectable HBV DNA by PCR are permitted with appropriate antiviral prophylaxis. Negative test results for hepatitis C virus (HCV) Note: Participants who are positive for HCV antibody must be negative for HCV RNA by PCR to be eligible for study participation. If HIV positive, HIV infection is controlled.

Have histologically confirmed FL, Grades 1 to 3A.

Must have been previously treated with at least 1 prior systemic chemotherapy, immunotherapy, or chemoimmunotherapy: Systemic therapy includes treatments such as: Rituximab monotherapy, Chemotherapy given with or without rituximab, Radioimmunoconjugates such as 90Y-ibritumomab tiuxetan and 131I-tositumomab. Systemic therapy does not include, for example: Local involved field radiotherapy for limited-stage disease, Helicobacter pylori eradication. Prior investigational therapies will be allowed provided the subject has received at least 1 prior systemic therapy as discussed in Inclusion Criterion #6a. Prior autologous/allogeneic hematopoietic stem cell transplant (HSCT) will be allowed. Prior chimeric antigen receptor T-cell therapy (CAR T) will be allowed.

Must have documented relapsed, refractory, or PD after treatment with systemic therapy (refractory defined as less than PR or disease progression <6 months after last dose).

Have measurable disease as defined by the Lugano Classification (Cheson, 2014; Appendix 5).

Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.

Within 7 days prior to randomization, all clinically significant toxicity related to a prior anticancer treatment (ie, chemotherapy, immunotherapy, and/or radiotherapy must have either resolved to Grade 1 per NCI CTCAE Version 5.0 OR are clinically stable and no longer clinically significant.

Have provided sufficient tumor tissue block or unstained slides for EZH2 mutation testing in all subjects to allow for stratification: If EZH2 mutation status is known from site-specific testing, subjects can be enrolled. Tumor tissue will be required for confirmatory testing of EZH2 status at study-specific laboratories. If the archival tumor sample was collected more than 24 months prior to the anticipated administration of the first dose (cycle 1 day 1), then a fresh biopsy must be provided. Fresh tumor biopsy is appropriate except for procedures deemed to result in unacceptable risk because of the anatomical location including brain, lung/mediastinum, pancreas, or endoscopic procedures extending beyond the esophagus, stomach, or bowel. Archival tumor biopsy sections mounted on slides are also acceptable.

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. Nitrosoureas - At least 6 weeks. Monoclonal and/or bispecific antibodies or 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 renal function defined as calculated creatinine clearance ≥30 mL/minute per the Cockcroft and Gault formula.

Adequate bone marrow function: Absolute neutrophil count (ANC) ≥1000/mm3 (≥1.0 × 10^9/L) if no lymphoma infiltration of bone marrow OR ANC ≥750/mm3 (≥75 × 10^9/L) with bone marrow infiltration Without growth factor support (filgrastim or pegfilgrastim) for at least 14 days. Platelets ≥75,000/mm3 (≥75 × 10^9/L) Evaluated at least 7 days after last platelet transfusion. Hemoglobin ≥9.0 g/dL May receive transfusion.

Adequate liver function: 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 subject has liver infiltration).

International normalized ratio (INR) ≤1.5 × ULN and activated partial thromboplastin time (aPTT) ≤1.5 × ULN (unless on warfarin, then INR ≤3.0). In subjects with thromboembolism risk, prophylactic anticoagulation, or antiplatelet therapy at investigator discretion is recommended.

Females of childbearing potential (FCBP) must have a negative urine or serum pregnancy tests (beta-human chorionic gonadotropin [β-hCG] tests with a minimum sensitivity of 25 mIU/mL or equivalent units of β-hCG) at screening within 10 to 14 days prior to first dose of study drug. The subject may not receive study drug until the study doctor has verified that the results of pregnancy tests are negative. All females will be considered to be of childbearing potential unless they are naturally postmenopausal (at least 24 months consecutively amenorrhoeic [amenorrhea following cancer therapy does not rule out childbearing potential] and without other known or suspected cause) or have been sterilized surgically (ie, total hysterectomy and/or bilateral oophorectomy, with surgery completed at least 1 month before dosing).

Females of childbearing potential (FCBP) enrolled must either practice complete abstinence or agree to use two reliable methods of contraception simultaneously. This includes ONE highly effective method of contraception and ONE additional effective contraceptive method. Contraception must begin at least 28 days prior to first dose of study drug, continue during study treatment (including during dose interruptions), and for 12 months after study drug discontinuation. Female subjects must also refrain from breastfeeding for 12 months following last dose of study drug. If the below contraception methods are not appropriate for the FCBP, she must be referred to a qualified contraception provider to determine the medically effective contraception method appropriate for the subject. The following are examples of highly effective and additional effective methods of contraception: Examples of highly effective methods: Intrauterine device (IUD), Hormonal (ovulation inhibitory combined [estrogen and progesterone] birth control pills or intravaginal/transdermal system, injections, implants, levonorgestrel-releasing intrauterine system [IUS], medroxyprogesterone acetate depot injections, ovulation inhibitory progesterone-only pills [e.g. desogestrel]) NOTE: There is a potential for tazemetostat interference with hormonal contraception methods due to enzymatic induction. Bilateral tubal ligation Partner's vasectomy (if medically confirmed [azoospermia] and sole sexual partner). Examples of additional effective methods: Male latex or synthetic condom, Diaphragm, Cervical Cap NOTE: Female subjects of childbearing potential exempt from these contraception requirements are subjects who practice complete abstinence from heterosexual sexual contact. True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (eg, calendar, ovulation, symptothermal, or post ovulation methods) and withdrawal are not acceptable methods of contraception.

All study participants enrolled must be registered into the applicable pregnancy prevention program (e.g. REVLIMID REMS in the US, Pregnancy Prevention Programme [PPP] in Europe, RevAid in Canada) for lenalidomide to be administered and be willing and able to comply with the requirements of the applicable program as appropriate for the country in which the drug is being used: Female subjects of childbearing potential (FCBP) must adhere to the scheduled pregnancy testing as required in the applicable pregnancy prevention program. During study treatment, FCBP must agree to have pregnancy testing weekly for the first 28 days of study participation and then every 28 days for FCBP with regular or no menstrual cycles OR every 14 days for FCBP with irregular menstrual cycles. FCBP must also have a pregnancy test at end of lenalidomide treatment, at days 14 and 28 following the last dose of lenalidomide and at overall treatment discontinuation (at the End-of-Treatment/30-day safety Follow-up visit). Female subjects exempt from this requirement are subjects who have been naturally postmenopausal for at least 24 consecutive months OR have had a total hysterectomy and/or bilateral oophorectomy.

Male subjects must either practice complete abstinence or agree to use a latex or synthetic condom, even with a successful vasectomy (medically confirmed azoospermia), during sexual contact with a pregnant female or FCBP from first dose of study drug, during study treatment (including during dose interruptions), and for 3 months after study drug discontinuation. NOTE: Male subjects must not donate semen or sperm from first dose of study drug, during study treatment (including during dose interruptions), and for 3 months after study drug discontinuation.

Exclusion criteria

Prior exposure to tazemetostat or other inhibitor(s) of EZH2.

Prior exposure to lenalidomide or drugs of the same class.

Grade 3b, mixed histology, or FL that has histologically transformed to diffuse large B-cell lymphoma (DLBCL) (subjects transformed from DLBCL to FL may be enrolled).

Has thrombocytopenia, neutropenia, or anemia of Grade ≥3 (per CTCAE Version 5.0 criteria) or any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or myeloproliferative neoplasm (MPN).

Has a prior history of T-cell lymphoblastic lymphoma (T-LBL)/T-cell acute lymphoblastic leukemia (T-ALL) or B-cell acute lymphoblastic leukemia (B-ALL).

Subjects with uncontrolled leptomeningeal metastases or brain metastases or history of previously treated brain metastases.

Subjects taking medications that are known strong CYP3A inhibitors and strong or moderate CYP3A inducers (including St. John's wort).

Are unwilling to exclude grapefruit juice, Seville oranges, and grapefruits from the diet and/or consumed within 1 week of the first dose of study drug and for the duration of the study.

Major surgery within 4 weeks before the first dose of study drug. Note: Minor surgery (eg, minor biopsy of extracranial site, central venous catheter placement, shunt revision) is permitted within 3 weeks prior to enrollment.

Are unable to take oral medication OR have malabsorption syndrome or any other uncontrolled gastrointestinal condition (eg, nausea, diarrhea, vomiting) that might impair the bioavailability of tazemetostat.

Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months of the first dose of study drug; or cardiac ventricular arrhythmia.

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 the last 3 months before starting tazemetostat. Note: Participants who have experienced deep vein thrombosis/pulmonary embolism more than 3 months before enrollment are eligible but are recommended to receive prophylaxis.

Have an active infection requiring systemic therapy.

Known hypersensitivity to any component of tazemetostat or lenalidomide; known severe hypersensitivity to any component of rituximab requiring hospitalization or resuscitation.

Active viral infection with or seropositive for HBV: HBV surface antigen (HBsAg) positive OR HBsAg negative, anti-HBs positive and/or anti-HBc positive with detectable HBV DNA. NOTE: Subjects who are HBsAg negative, anti-HBs positive and/or anti-HBc positive, but with undetectable viral DNA and normal ALT are eligible. Subjects who are seropositive due to HBV vaccination (HBsAg negative, HBV surface antibody [anti-HBs] positive, and HBV core antibody [anti-HBc] negative) are eligible.

Active viral infection with hepatitis C virus (as measured by positive HCV antibody and detectable viral RNA, HIV), or known active infection with human T-cell lymphotropic virus. NOTE: Subjects with a history of hepatitis C infection (HCV antibody reactive) who have normal ALT and undetectable HCV RNA are eligible.

Any other medical or social condition that, in the Investigator's judgment, will interfere with a participant's ability to provide informed consent, to receive study drugs, or meet study demands, or that substantially increases the risk associated with the subject's participation in the study, or that may interfere with interpretation of results.

Female subjects who are pregnant or lactating/breastfeeding.

Subjects who have undergone a solid organ transplant.

Subjects with malignancies other than FL. Exception: Subjects with another malignancy who have been disease-free for 3 years, or subjects with a history of a completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.

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Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2020-06-11

Primary completion: 2026-03-01

Study completion finish: 2029-03-01

Study type

TREATMENT

Phase

PHASE3

Trial ID

NCT04224493

Intervention or treatment

DRUG: Tazemetostat

DRUG: Placebo oral tablet

COMBINATION_PRODUCT: Lenalidomide

COMBINATION_PRODUCT: Rituximab

Conditions

• Follicular Lymphoma
• Relapsed/Refractory Follicular Lymphoma
• Refractory Follicular Lymphoma

Condition: Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma and more
DRUG: Tazemetostat and other drugs
Adelaide, South Australia, Australia and more
Sponsor: Epizyme, Inc.

You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

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Find a site

Closest Location:

Royal Adelaide Hospital

Research sites nearby

Select from list below to view details:

Royal Adelaide Hospital
Adelaide, South Australia, Australia
Flinders Medical Centre
Bedford Park, South Australia, Australia
Monash Health
Clayton, Victoria, Australia
Barwon Health, University Hospital Geelong
Geelong, Victoria, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Tazemetostat + R2 arm Stage 1 (Phase 1b): This phase is now completed. * Tazemetostat was escalated from a starting dose of 400 mg PO twice daily to 600 mg PO twice daily to 800 mg PO twice daily in 28-day cycles. * Rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1; then on day 1 of cycles 2 to 5. * Lenalidomide 20 mg or 10 mg (if creatinine clearance ≥60 mL/minute or \<60 mL/minute), administred PO QD on days 1 to 21 for 12 cycles. Stage 2: * Tazemetostat 800 mg administered PO twice daily in continuous 28-day cycles. * Rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1; then on day 1 of cycles 2 to 5. * Lenalidomide 20 mg or 10 mg (if creatinine clearance ≥60 mL/minute or \<60 mL/minute), PO QD on days 1 to 21 for 12 cycles. Maintenance Therapy (Stages 1 and 2): Tazemetostat will be administered as monotherapy at an 800 mg twice daily dose for up to 2 years after the initial 12 months of combination therapy.	DRUG: Tazemetostat Stage 1 (Phase 1b): Tazemetostat was escalated from a starting dose of 400 mg orally twice daily to 600 mg orally twice daily to 800 mg PO twice daily in 28-day cycles as tolerated in a standard 3 + 3 design. Tazemetostat will be administered as monotherapy at an 800 mg twice daily dose for up to 2 years after the initial 12 months of combination therapy.
PLACEBO_COMPARATOR: Placebo + R2 Arm Stage 2: * Placebo administered PO twice daily in continuous 28-day cycles. * Rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1; then on day 1 of cycles 2 to 5. * Lenalidomide 20 mg or 10 mg (if creatinine clearance ≥60 mL/minute or \<60 mL/minute), administered PO QD on days 1 to 21 for 12 cycles. Maintenance Therapy (Stage 2): Placebo will be administered as monotherapy twice daily dose for up to 2 years after the initial 12 months of combination therapy. During maintenance, placebo will be continued until disease progression or unacceptable toxicity, or participant withdraws consent.	DRUG: Placebo oral tablet Stage 2: Placebo administered orally twice daily in continuous 28-day cycles. Placebo will be administered as monotherapy twice daily dose for up to 2 years after the initial 12 months of combination therapy.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Tazemetostat + R2 arm

Stage 1 (Phase 1b): This phase is now completed.
* Tazemetostat was escalated from a starting dose of 400 mg PO twice daily to 600 mg PO twice daily to 800 mg PO twice daily in 28-day cycles.
* Rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1; then on day 1 of cycles 2 to 5.
* Lenalidomide 20 mg or 10 mg (if creatinine clearance ≥60 mL/minute or \<60 mL/minute), administred PO QD on days 1 to 21 for 12 cycles.
Stage 2:
* Tazemetostat 800 mg administered PO twice daily in continuous 28-day cycles.
* Rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1; then on day 1 of cycles 2 to 5.
* Lenalidomide 20 mg or 10 mg (if creatinine clearance ≥60 mL/minute or \<60 mL/minute), PO QD on days 1 to 21 for 12 cycles.
Maintenance Therapy (Stages 1 and 2):
Tazemetostat will be administered as monotherapy at an 800 mg twice daily dose for up to 2 years after the initial 12 months of combination therapy.

DRUG: Tazemetostat

Stage 1 (Phase 1b):
Tazemetostat was escalated from a starting dose of 400 mg orally twice daily to 600 mg orally twice daily to 800 mg PO twice daily in 28-day cycles as tolerated in a standard 3 + 3 design. Tazemetostat will be administered as monotherapy at an 800 mg twice daily dose for up to 2 years after the initial 12 months of combination therapy.

PLACEBO_COMPARATOR: Placebo + R2 Arm

Stage 2:
* Placebo administered PO twice daily in continuous 28-day cycles.
* Rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1; then on day 1 of cycles 2 to 5.
* Lenalidomide 20 mg or 10 mg (if creatinine clearance ≥60 mL/minute or \<60 mL/minute), administered PO QD on days 1 to 21 for 12 cycles.
Maintenance Therapy (Stage 2):
Placebo will be administered as monotherapy twice daily dose for up to 2 years after the initial 12 months of combination therapy. During maintenance, placebo will be continued until disease progression or unacceptable toxicity, or participant withdraws consent.

DRUG: Placebo oral tablet

Stage 2:
Placebo administered orally twice daily in continuous 28-day cycles. Placebo will be administered as monotherapy twice daily dose for up to 2 years after the initial 12 months of combination therapy.

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
Recommended Phase 3 Dose (RP3D) of tazemetostat in combination with rituximab and lenalidomide (R2)	The safety and tolerability of tazemetostat in combination with R2 in subjects with R/R FL will be evaluated. RP3D of tazemetostat for further evaluation in phase 3 will be selected as assessed by the occurrence of treatment-emergent dose-limiting toxicities (DLTs) and adverse events (AEs).	Subjects are evaluated for DLTs during the first 28-day cycle. The RP3D for Phase 3 was selected at the end of Stage 1
Progression-Free Survival (PFS) in the Intent-to-treat wild-type (ITT-WT) population	PFS is defined as the time from the date of randomization to the time of confirmed disease progression per the 2014 Lugano Classification or death, whichever occurs first, as assessed by Investigators.	Stage 2: Up to 72 months
PFS in the Intent-to-treat mutant-type (ITT-MT) population	PFS is defined as the time from the date of randomization to the time of confirmed disease progression per the 2014 Lugano Classification or death, whichever occurs first, as assessed by Investigators.	Stage 2: Up to 72 months

Secondary outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
Pharmacokinetics (PK) of tazemetostat: Maximum (peak) Observed Plasma Drug Concentration (Cmax).	Cmax will be recorded from the PK blood samples collected.	Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle)
PK of tazemetostat, EPZ 6930 (desethyl metabolite), and lenalidomide as data permit: Time to Maximum Observed Drug Concentration (Tmax)	Not Specified	Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle)
PK of tazemetostat: area under the plasma concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration [AUC(0-t)],	Not Specified	Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle)
PK of tazemetostat: area under the plasma concentration-time curve (AUC) from time 0 to infinity [AUC(0-∞)]	Not Specified	Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle)
The apparent terminal elimination half-life (t1/2) of tazemetostat, EPZ 6930 (desethyl metabolite), and lenalidomide as data permit	Not Specified	Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle)
Complete Response Rate (CRR) in ITT-WT population	CRR is defined as the proportion of participants achieving CR according to the 2014 Lugano Classification, as assessed by the Investigator and a blinded Independent Review Committee (IRC).	Stage 2: Up to 96 months
CRR in ITT-MT population	CRR is defined as the proportion of participants achieving CR according to the 2014 Lugano Classification, as assessed by the Investigator and a blinded IRC.	Stage 2: Up to 96 months
CRR in the Relapsed/Refractory (R/R) Follicular Lymphoma (FL) population regardless of mutation status	CRR is defined as the proportion of participants achieving CR according to the 2014 Lugano Classification, as assessed by the Investigator and a blinded IRC.	Stage 2: Up to 96 months
Objective Response Rate (ORR) in the ITT-WT population	ORR is defined as the proportion of participants achieving a best overall response (BOR) of partial response (PR) or complete response (CR) according to the 2014 Lugano Classification, as assessed by the Investigator and a blinded IRC.	Stage 2: Up to 96 months
ORR in the ITT-MT population	ORR is defined as the proportion of participants achieving a best overall response (BOR) of partial response (PR) or complete response (CR) according to the 2014 Lugano Classification, as assessed by the Investigator and a blinded IRC.	Stage 2: Up to 96 months
ORR in the R/R FL population regardless of mutation status	ORR is defined as the proportion of participants achieving a best overall response (BOR) of partial response (PR) or complete response (CR) according to the 2014 Lugano Classification, as assessed by the Investigator and a blinded IRC.	Stage 2: Up to 96 months
Overall Survival (OS) in the ITT-WT population	OS is defined as the time from the date of randomization until death due to any cause.	Stage 2: Up to 96 months
OS in the ITT-MT population	Not Specified	Stage 2: Up to 96 months
OS in the R/R FL population regardless of mutation status	Not Specified	Stage 2: Up to 96 months
PFS in the ITT-WT population, assessed by a blinded IRC	Not Specified	Stage 2: Up to 96 months
PFS in the ITT-MT population, assessed by a blinded IRC	Not Specified	Stage 2: Up to 96 months
PFS in the R/R FL population regardless of mutation status, assessed by a blinded IRC	Not Specified	Stage 2: Up to 96 months
PFS in the R/R FL population regardless of mutation status, assessed by the Investigator	Not Specified	Stage 2: Up to 96 months
Duration Of Response (DOR) in the ITT-WT population	DOR is defined as the time from initial CR or PR to documented progression or death due to any cause, whichever occurs first, for those participants with a CR or PR, as assessed by the Investigator and by a blinded IRC.	Stage 2: Up to 96 months
DOR in the ITT-MT population	DOR is defined as the time from initial CR or PR to documented progression or death due to any cause, whichever occurs first, for those participants with a CR or PR, as assessed by the Investigator and by a blinded IRC.	Stage 2: Up to 96 months
DOR in the R/R FL population regardless of mutation status	DOR is defined as the time from initial CR or PR to documented progression or death due to any cause, whichever occurs first, for those participants with a CR or PR, as assessed by the Investigator and by a blinded IRC.	Stage 2: Up to 96 months
Duration Of Complete Response (DOCR) in the ITT-WT population	DOCR is defined as the time from initial CR to documented progression or death due to any cause, whichever occurs first, for those participants with CR, assessed by the Investigator and by a blinded IRC.	Stage 2: Up to 96 months
DOCR in the ITT-MT population	DOCR is defined as the time from initial CR to documented progression or death due to any cause, whichever occurs first, for those participants with CR, assessed by the Investigator and by a blinded IRC.	Stage 2: Up to 96 months
DOCR in the R/R FL population regardless of mutation status	DOCR is defined as the time from initial CR to documented progression or death due to any cause, whichever occurs first, for those participants with CR, assessed by the Investigator and by a blinded IRC.	Stage 2: Up to 96 months
Disease Control Rate (DCR) in the ITT-WT population	DCR, defined as the proportion of participants with best overall response of CR, PR, or stable disease (SD) lasting 12 or more months, as assessed by the Investigator and by a blinded IRC.	Stage 2: Up to 96 months
DCR in the ITT-MT population	DCR, defined as the proportion of participants with best overall response of CR, PR, or stable disease (SD) lasting 12 or more months, as assessed by the Investigator and by a blinded IRC.	Stage 2: Up to 96 months
DCR in the R/R FL population regardless of mutation status	DCR, defined as the proportion of participants with best overall response of CR, PR, or stable disease (SD) lasting 12 or more months, as assessed by the Investigator and by a blinded IRC.	Stage 2: Up to 96 months
Population PK parameters of oral clearance (CL/F) of tazemetostat	CL/F will be used to generate estimates of tazemetostat AUC	Stage 2: In cycles 2, 4, 6, and 12 at Day 1 (28 days cycle)
Population PK parameters of oral volume of distribution (Vd/F) of tazemetostat.	Not Specified	Stage 2: In cycles 2, 4, 6, and 12 at Day 1 (28 days cycle)
Population PK parameters of first-order absorption rate constant (Ka) for tazemetostat.	Not Specified	Stage 2: In cycles 2, 4, 6, and 12 at Day 1 (28 days cycle)
Percentage of Participants Experiencing 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.	Up to 36 months
Percentage of Participants with Clinically Significant Changes in Physical Examination	Percentage of participants with clinically significant changes in physical examination findings will be reported. The clinical significance will be graded by the investigator according to the National Cancer Institute Common Terminology Criteria for AEs (CTCAE) Version 5.0.	Up to 36 months
Percentage of Participants with Clinically Significant Changes in Vital Signs	Percentage of participants with clinically significant changes in vital signs findings will be reported. The clinical significance will be graded by the investigator according to the National Cancer Institute Common Terminology Criteria for AEs (CTCAE) Version 5.0.	Up to 36 months
Percentage of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Readings	Percentage of participants with clinically significant changes in ECG Readings will be reported. The clinical significance will be graded by the investigator according to the National Cancer Institute Common Terminology Criteria for AEs (CTCAE) Version 5.0.	Up to 72 months
Performance status evaluated by Eastern Cooperation Oncology Group (ECOG)	ECOG is a 6-point performance status scale used to assess performance using PA as a key indicator (e.g., 0 = fully active, 2 = up and about more than 50% of walking hours, 5 = dead) Performance status will be assessed per usual clinical practice and will be recorded in the medical record.	Up to 72 months
Duration of Study Drug Exposure	Duration of exposure to study drug will be reported.	Up to 36 months
Percentage of study drug taken by participants	Not Specified	Up to 36 months
Quality of life questionnaires evaluation	Evaluate and compare health-related quality of life as measured by the EuroQOL 5-Dimension 5-Level (EQ-5D-5L) instrument and the Functional Assessment of Cancer Therapy -Lymphoma (FACT-Lym)	Up to 36 months

Frequently Asked Questions

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References

Clinical Trials Gov: A Study to Assess the Efficacy, Safety, Pharmacodynamics, and Pharmacokinetics of Tazemetostat in Combination With Lenalidomide Plus Rituximab Versus Placebo in Combination With Lenalidomide Plus Rituximab in Adult Patients at Least 18 Years of Age With Relapsed/Refractory Follicular Lymphoma.