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Tazemetostat for the Treatment of Relapsed/Refractory Follicular Lymphoma

Primary Purpose

Relapsed/Refractory Follicular Lymphoma With EZH2

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Tazemetostat
Sponsored by
Hutchison Medipharma Limited
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsed/Refractory Follicular Lymphoma With EZH2

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Fully aware this study and signed the informed consent form in voluntary manner, and willing and able to comply with the study procedure;
  2. Age ≥18 years;
  3. Patients with histologically confirmed R/R FL (Grades 1, 2, 3a)
  4. Patients must have one measurable lesion
  5. Life expectancy ≥ 12 weeks;
  6. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2
  7. Adequate bone marrow function, renal function and hepatic function:
  8. Currently human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) or cytomegalovirus (CMV) is inactive:
  9. Female patients of childbearing potential must agree to adopt dual contraceptive method

Exclusion Criteria:

  1. Previous use of Tazemetostat or other EZH2 inhibitors;
  2. Patients with invasion of lymphoma to the central nervous system (CNS) or the pia mater;
  3. Previous bone marrow malignancies,
  4. Abnormalities associated with MDS and myeloproliferative neoplasms observed by cytogenetic testing and DNA sequencing;

Sites / Locations

  • Shanghai Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Cohort 1 based on the EZH2 mutations

Cohort 2 based on the EZH2 mutations,

Arm Description

MT patients with R/R FL; planned enrollment number: 19;

WT patients with R/R FL; planned enrollment number: 20;

Outcomes

Primary Outcome Measures

efficacy of Tazemetostat in EZH2 (MT) (Cohort 1)
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)
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)
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
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
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
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
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.

Full Information

First Posted
June 28, 2022
Last Updated
September 29, 2022
Sponsor
Hutchison Medipharma Limited
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1. Study Identification

Unique Protocol Identification Number
NCT05467943
Brief Title
Tazemetostat for the Treatment of Relapsed/Refractory Follicular Lymphoma
Official Title
A Multicenter, Open-label, Phase II Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Tazemetostat for the Treatment of Patients With Relapsed/Refractory Follicular Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 29, 2022 (Actual)
Primary Completion Date
June 2023 (Anticipated)
Study Completion Date
February 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hutchison Medipharma Limited

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No

5. Study Description

Brief Summary
Treating Relapsed/Refractory Follicular Lymphoma with Tazemetostat
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed/Refractory Follicular Lymphoma With EZH2

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
All patients will be enrolled to Cohort 1 and 2 based on the EZH2 mutations, respectively: Cohort 1: MT patients with R/R FL; planned enrollment number: 19; Cohort 2: WT patients with R/R FL; planned enrollment number: 20; Both cohorts have same dose administered: 800 mg, twice per day (BID), continuously, at a suggested interval of 12 hours between two doses.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
39 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1 based on the EZH2 mutations
Arm Type
Experimental
Arm Description
MT patients with R/R FL; planned enrollment number: 19;
Arm Title
Cohort 2 based on the EZH2 mutations,
Arm Type
Experimental
Arm Description
WT patients with R/R FL; planned enrollment number: 20;
Intervention Type
Drug
Intervention Name(s)
Tazemetostat
Intervention Description
All patients will receive 800 mg of Tazemetostat, BID, administered in continuous 28-day therapeutic cycle
Primary Outcome Measure Information:
Title
efficacy of Tazemetostat in EZH2 (MT) (Cohort 1)
Description
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]
Time Frame
22 months
Secondary Outcome Measure Information:
Title
efficacy of Tazemetostat in EZH2 (WT) (Cohort 2)
Description
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.
Time Frame
22 months
Title
safety of Tazemetostat in EZH2 (WT) (Cohort 2)
Description
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.
Time Frame
22 months
Title
Geomean maximum concentration (Cmax) of tazemetostat and its metabolite EPZ-6930 in blood
Description
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.
Time Frame
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.
Title
Median time to reach maximum concentration (Tmax) of tazemetostat and its metabolite EPZ-6930 in blood
Description
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.
Time Frame
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.
Title
Geomean area under the drug concentration-time curve (AUC) of tazemetostat and its metabolite EPZ-6930 after administration of tazemetostat
Description
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.
Time Frame
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
Title
Geomean minimum observed concentration at steady-state (Cmin) of tazemetostat and its metabolite EPZ-6930 in blood
Description
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.
Time Frame
Cycle1Day15, Cycle2Day1 and Cycle3Day1: predose of first administration

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Fully aware this study and signed the informed consent form in voluntary manner, and willing and able to comply with the study procedure; Age ≥18 years; Patients with histologically confirmed R/R FL (Grades 1, 2, 3a) Patients must have one measurable lesion Life expectancy ≥ 12 weeks; Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2 Adequate bone marrow function, renal function and hepatic function: Currently human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) or cytomegalovirus (CMV) is inactive: Female patients of childbearing potential must agree to adopt dual contraceptive method Exclusion Criteria: Previous use of Tazemetostat or other EZH2 inhibitors; Patients with invasion of lymphoma to the central nervous system (CNS) or the pia mater; Previous bone marrow malignancies, Abnormalities associated with MDS and myeloproliferative neoplasms observed by cytogenetic testing and DNA sequencing;
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Tinghua Song
Phone
19512230542
Email
tinghuas@hutch-med.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Junning Cao, MD
Organizational Affiliation
Shanghai Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shanghai Cancer Center
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Junning Cao, MD
Phone
13651680209
Email
cao_junning@126.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Tazemetostat for the Treatment of Relapsed/Refractory Follicular Lymphoma

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