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.

Running, not enrolling · Phase 3 · Has a placebo group

Conditions studied: Relapsed/Refractory Follicular Lymphoma, Follicular Lymphoma, Refractory Follicular Lymphoma

In brief

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.

Key facts

Study ID

NCT04224493

Run by

Epizyme, Inc.

People needed

599

Starts

2020-06-11

Expected to finish

2029-03-01

Last updated by the study team

2026-07-30

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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, or per country adult legal age regulations, 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. Based on Cancer Clinical Trial Eligibility Criteria: Patients with HIV, Hepatitis B Virus, or Hepatitis C Virus Infections - Guidance for Industry (https://www.fda.gov/media/121319/download), patients with HIV should be considered eligible if they have CD4+ T-cell counts ≥ 350 cells/uL and in general, if they have not had an opportunistic infection within the past 12 months. Other exclusion criteria should be considered regarding the drug-drug interaction if antiviral drugs are used. Therefore, in case of controlled HIV infection, since antiviral drugs are used, trial patients should be on established ART for at least 4 weeks and have an HIV viral load less than 400 copies/mL prior to enrolment.
• Have histologically confirmed FL, Grades 1 to 3A.
• Must have been previously treated with at least 1 prior systemic chemotherapy, immunotherapy, or chemoimmunotherapy:
• a. Systemic therapy includes treatments such as:
• i. Rituximab monotherapy
• ii. Chemotherapy given with or without rituximab
• iii. Radioimmunoconjugates such as 90Y-ibritumomab tiuxetan and 131I-tositumomab.
• b. Systemic therapy does not include, for example:
• i. Local involved field radiotherapy for limited-stage disease
• ii. Helicobacter pylori eradication
• c. Prior investigational therapies will be allowed provided the subject has received at least 1 prior systemic therapy as discussed in Inclusion Criterion #6a.
• d. Prior autologous/allogeneic hematopoietic stem cell transplant (HSCT) will be allowed.
• e. 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
• a. 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.

You may not qualify if…

• All Subjects
• 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.
• a. 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.
• a. 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.

Where it is running

• Arizona Oncology Associates - Tuscon-Rusadill Road — Tucson, Arizona, United States
• TOI - Clinical Research — Cerritos, California, United States
• UCSF Fresno — Clovis, California, United States
• UC San Diego Health Sciences — La Jolla, California, United States
• UCLA Clinical Research Unit Hematology/Oncology — Santa Monica, California, United States
• Rocky Mountain Cancer Centers (RMCC) - Boulder — Boulder, Colorado, United States
• St. Mary's Hospital and Regional Medical Center - St. Mary's — Grand Junction, Colorado, United States
• Cancer Specialists of North Florida — Fleming Island, Florida, United States
• Florida Cancer Specialists & Research Institute (FCS) - Fort Myers Cancer Center — Fort Myers, Florida, United States
• Mayo Clinic — Jacksonville, Florida, United States
• Florida Cancer Affiliates/Ocala Oncology - Clinic — Ocala, Florida, United States
• BRCR Medical Center, INC — Plantation, Florida, United States
• Florida Cancer Specialists — St. Petersburg, Florida, United States
• Florida Cancer Specialists - Panhandle — Tallahassee, Florida, United States
• H Lee Moffitt Cancer Center and Research Institute I — Tampa, Florida, United States
• Florida Cancer Specialists & Research Institute (FCS) - Atlantis — West Palm Beach, Florida, United States
• University of Chicago — Chicago, Illinois, United States
• Illinois Cancer Specialists — Niles, Illinois, United States
• University of Michigan Comprehensive Cancer Center — Ann Arbor, Michigan, United States
• St. Joseph Mercy Hospital — Ypsilanti, Michigan, United States
• Mayo Clinic - Rochester — Rochester, Minnesota, United States
• University Of Nebraska Medical Center — Omaha, Nebraska, United States
• Astera Cancer Care — East Brunswick, New Jersey, United States
• Astera Cancer Center — East Brunswick, New Jersey, United States
• Southern Cancer Center — Mobile, Alabama, United States

Full record on ClinicalTrials.gov

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