Tazemetostat for the Treatment of Relapsed/Refractory Follicular Lymphoma

Sponsor
Hutchison Medipharma Limited (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT05467943
Collaborator
(none)
39
1
2
19.1
2

Study Details

Study Description

Brief Summary

Treating Relapsed/Refractory Follicular Lymphoma with Tazemetostat

Condition or Disease Intervention/Treatment Phase
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

Study Type:
Interventional
Anticipated Enrollment :
39 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Intervention 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.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)
Primary Purpose:
Treatment
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
Anticipated Study Start Date :
Jul 1, 2022
Anticipated Primary Completion Date :
Jun 1, 2023
Anticipated Study Completion Date :
Feb 1, 2024

Arms and Interventions

Arm Intervention/Treatment
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

  1. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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;

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.
Responsible Party:
Hutchison Medipharma Limited
ClinicalTrials.gov Identifier:
NCT05467943
Other Study ID Numbers:
  • 2021-TAZ-00CH1
First Posted:
Jul 21, 2022
Last Update Posted:
Jul 22, 2022
Last Verified:
Jul 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
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
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 22, 2022