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Study of Tazemetostat as Single Agent in Solid Tumors or B-cell Lymphomas and in Combination With Prednisolone in DLBCL | Clinical Trials | Clareo Health

COMPLETEDPHASE1/PHASE2

Study of Tazemetostat as Single Agent in Solid Tumors or B-cell Lymphomas and in Combination With Prednisolone in DLBCL

An Open-Label, Multicenter, Phase 1/2 Study of Tazemetostat as a Single Agent in Subjects With Advanced Solid Tumors or With B-cell Lymphomas and Tazemetostat in Combination With Prednisolone in Subjects With Diffuse Large B Cell Lymphoma

NCT01897571•Epizyme, Inc.

View on ClinicalTrials.gov

Summary

This is an open-label, multicenter, Phase 1/2 study of tazemetostat as a single agent in subjects with advanced solid tumors or with B-cell lymphomas and tazemetostat in combination with prednisolone in subjects with diffuse large B-cell lymphoma (DLBCL).

Detailed Description

This is a multicenter, open-label, Phase 1/2 study conducted in two parts: The Phase 1 part comprised dose escalation and expansion to establish the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) when tazemetostat was given twice daily (BID) orally on a continuous basis. Additionally, in separate cohorts in Phase 1, the effect of food on the bioavailability of tazemetostat as well as the drug-drug interaction (DDI) potential of tazemetostat were evaluated. The Phase 2 part was initiated once the RP2D was established. Phase 2 enrolled subjects with relapsed/ refectory (R/R) DLBCL (Cohorts 1-3 and 6) and subjects with R/R FL (Cohorts 4 and 5) for the determination of efficacy and safety of tazemetostat monotherapy (Cohorts 1-5) and of tazemetostat in combination with prednisolone (Cohort 6) with placement determined by centrally confirmed histology, cell of origin (COO), and enhancer of zeste homologue 2 (EZH2) mutation status.

Eligibility

Age

16 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. Phase 1: Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Phase 2: ECOG performance status of 0 to 2.
•2. Life expectancy of at least 3 months before starting tazemetostat.
•3. Voluntary agreement to provide written informed consent and willing to adhere to all protocol requirements
•4. Subjects with Hepatitis B or C are eligible on the condition that subjects have adequate liver function and are hepatitis B surface antigen negative and/or have undetectable hepatitis C virus (HCV) RNA.
•5. Adequate renal and liver function
•6. Phase 1: Males or females aged ≥ 16 years at time of informed consent. Phase 2: Males or females aged ≥ 18 years at the time of informed consent .
•7. Females must not be lactating or pregnant at screening or baseline as documented by a negative pregnancy test All females will be considered to be of childbearing potential unless they are postmenopausal (at least 12 months consecutive amenorrheic, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, total hysterectomy or bilateral oophorectomy, all with surgery at least 1 month before dose). Females of childbearing potential must not have had unprotected sexual intercourse within 30 days prior to study entry and must agree to use a highly effective method of contraception, from the last menstrual period prior to randomization, during Treatment Cycles, and for 6 months after the last final dose of study drug; any male partner must use a condom.
•8. Male subjects must have had a successful vasectomy (with confirmed azoospermia) or they and their female partner must meet the criteria above (ie, not of childbearing potential or practicing highly effective contraception and use a condom throughout the study period and for 3 months after study drug discontinuation). Nonvasectomized male subjects must also agree to refrain from donating sperm from first dose of tazemetostat until 3 months following the last dose of tazemetostat
•9. Phase 1 only: Histologically and/or cytologically confirmed advanced or metastatic solid tumor or B-cell lymphomas that have progressed after treatment with approved therapies or for which there are no standard therapies available.
•10. Phase 2, Groups 1-6 only: Subjects must satisfy all of the following criteria:
+9 more criteria

Exclusion Criteria

•1. Prior exposure to tazemetostat or other inhibitor(s) of EZH2.
•2. Subjects with leptomeningeal metastases or brain metastases or history of previously treated brain metastases.
•3. Has thrombocytopenia, neutropenia, or anemia of Grade ≥3 (per CTCAE 4.03 criteria) and any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS).
•4. Has a prior history of T-cell lymphoblastic lymphoma(T-LBL) or T-cell lymphoblastic leukemia (T-ALL).
•5. Subjects taking medications that are known strong CYP3A inhibitors and strong or moderate CYP3A inducers (including St. Johns Wort) 6. Subjects unwilling to remove Seville oranges, grapefruit juice and grapefruit from their diet.
•6. Any unstable or unresolved prior treatment-related (i.e. chemotherapy, immunotherapy, radiotherapy) toxicities at time of enrollment.
•7. Major surgery within 4 weeks before the first dose of study drug. .
•8. Inability to take oral medication, or malabsorption syndrome or any other uncontrolled gastrointestinal condition (e.g., nausea, diarrhea, or vomiting) that might impair the bioavailability of tazemetostat.
•9. 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.
•10. Venous thrombosis or pulmonary embolism within the last 3 months before starting tazemetostat.
+5 more criteria

Locations (52)

Birmingham, Alabama, United States

Duarte, California, United States

Santa Barbara, California, United States

Aurora, Colorado, United States

Washington D.C., District of Columbia, United States

Ocala, Florida, United States

Ann Arbor, Michigan, United States

New York, New York, United States

Houston, Texas, United States

San Antonio, Texas, United States

Key Dates

Start Date

June 13, 2013

Primary Completion Date

August 24, 2021

Completion Date

November 2, 2021

Last Updated

March 26, 2024

Enrollment

400

ACTUAL participants

Conditions

B-cell Lymphomas (Phase 1)Advanced Solid Tumors (Phase 1)Diffuse Large B-cell Lymphoma (Phase 2)Follicular Lymphoma (Phase 2)Transformed Follicular LymphomaPrimary Mediastinal Large B-Cell Lymphoma

Interventions

Tazemetostat

DRUG

Prednisolone

DRUG

Tazemetostat

DRUG