Tazemetostat for the Treatment of Relapsed/Refractory Follicular Lymphoma
Study Details
Study Description
Brief Summary
Treating Relapsed/Refractory Follicular Lymphoma with Tazemetostat
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2 |
Detailed Description
This is an open-label, monotherapy, Phase II Study clinical study. The objective is to evaluate the efficacy, safety, and pharmacokinetics of Tazemetostat in the treatment of patients with relapsed/refractory follicular lymphoma. It is planned to enroll 39 Chinese patients in 2 cohorts.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Cohort 1 based on the EZH2 mutations MT patients with R/R FL; planned enrollment number: 19; |
Drug: Tazemetostat
All patients will receive 800 mg of Tazemetostat, BID, administered in continuous 28-day therapeutic cycle
|
Experimental: Cohort 2 based on the EZH2 mutations, WT patients with R/R FL; planned enrollment number: 20; |
Drug: Tazemetostat
All patients will receive 800 mg of Tazemetostat, BID, administered in continuous 28-day therapeutic cycle
|
Outcome Measures
Primary Outcome Measures
- efficacy of Tazemetostat in EZH2 (MT) (Cohort 1) [22 months]
Objective response rate (ORR) of Cohort 1 evaluated by the Independent Review Committee (IRC) [based on the International Working Group-Non-Hodgkin's Lymphoma [IWG-NHL] (Cheson) 2007]
Secondary Outcome Measures
- efficacy of Tazemetostat in EZH2 (WT) (Cohort 2) [22 months]
Overall survival (OS) of Cohort 1 and 2. OS: defined as the time from the first dose of study drug to death for any cause.
- safety of Tazemetostat in EZH2 (WT) (Cohort 2) [22 months]
The incidence and severity of treatment emergent adverse events (TEAEs). Occurrence of AEs (including SAEs) will be monitored based on the changes in vital signs, physical examination, 12-lead ECG and laboratory examinations. The severity of AEs will be graded based on NCI CTCAE V5.0.
- Geomean maximum concentration (Cmax) of tazemetostat and its metabolite EPZ-6930 in blood [Cycle1Day1: predose of first administration; 0.5, 1, 2, 4, 6, 8, and 12 hours postdose. Cycle1Day15: predose of first administration ; 0.5, 1, 2, 4, 6, 8, and 12 hours postdose. Cycle2Day1 and Cycle3Day1: predose of first administration.]
Cmax is defined as the maximum observed concentration that a drug achieves in a test area of the body after the drug has been administered. Plasma concentration-time profiles of tazemetostat and EPZ-6930 will be plotted using non-compartmental analysis and will be analyzed to determine Cmax. Cmax will be summarized as the geomean and geomean CV% for all participants.
- Median time to reach maximum concentration (Tmax) of tazemetostat and its metabolite EPZ-6930 in blood [Cycle1Day 1: predose of first administration; 0.5, 1, 2, 4, 6, 8, and 12 hours postdose. Cycle1Day15: predose of first administration; 0.5, 1, 2, 4, 6, 8, and 12 hours postdose. Cycle2Day1 and Cycle3Day1: predose of first administration.]
Tmax is defined as the time from dosing to reach the maximum observed concentration a drug achieves in a specified compartment or test area of the body after the drug has been administered. Plasma concentration-time profiles of tazemetostat and EPZ-6930 will be plotted using non-compartmental analysis and will be analyzed to determine Tmax. Tmax will be summarized as the median (min, max) for all participants.
- Geomean area under the drug concentration-time curve (AUC) of tazemetostat and its metabolite EPZ-6930 after administration of tazemetostat [Cycle1Day1: predose of first administration; 0.5, 1, 2, 4, 6, 8, and 12 hours postdose. Cycle1Day15: predose of first administration; 0.5, 1, 2, 4, 6, 8, and 12 hours postdose]
AUC represents the total drug exposure over a defined period of time. AUC will be calculated using the linear trapezoidal rule. Plasma concentrations of tazemetostat and EPZ-6930 will be analyzed using a non-compartmental analysis approach to determine individual participant estimates of AUC. AUC will be summarized as the geomean and geomean CV% for all participants.
- Geomean minimum observed concentration at steady-state (Cmin) of tazemetostat and its metabolite EPZ-6930 in blood [Cycle1Day15, Cycle2Day1 and Cycle3Day1: predose of first administration]
Cmin is defined as the minimum observed concentration at steady-state during one dosing interval. Cmin will be summarized as the geomean and geomean CV% for all participants.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Fully aware this study and signed the informed consent form in voluntary manner, and willing and able to comply with the study procedure;
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Age ≥18 years;
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Patients with histologically confirmed R/R FL (Grades 1, 2, 3a)
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Patients must have one measurable lesion
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Life expectancy ≥ 12 weeks;
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Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2
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Adequate bone marrow function, renal function and hepatic function:
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Currently human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) or cytomegalovirus (CMV) is inactive:
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Female patients of childbearing potential must agree to adopt dual contraceptive method
Exclusion Criteria:
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Previous use of Tazemetostat or other EZH2 inhibitors;
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Patients with invasion of lymphoma to the central nervous system (CNS) or the pia mater;
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Previous bone marrow malignancies,
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Abnormalities associated with MDS and myeloproliferative neoplasms observed by cytogenetic testing and DNA sequencing;
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Shanghai Cancer Center | Shanghai | Shanghai | China | 200032 |
Sponsors and Collaborators
- Hutchison Medipharma Limited
Investigators
- Principal Investigator: Junning Cao, MD, Shanghai Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2021-TAZ-00CH1