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Study of E7777 in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma and Cutaneous T-cell Lymphoma

Primary Purpose

Peripheral T-cell Lymphoma, Cutaneous T-cell Lymphoma

Status

Completed

Phase

Phase 2

Locations

Japan

Study Type

Interventional

Intervention

E7777

About this trial

This is an interventional treatment trial for Peripheral T-cell Lymphoma focused on measuring Peripheral T-cell lymphoma, Cutaneous T-cell lymphoma, E7777, Phase 2

Eligibility Criteria

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

Inclusion Criteria:

Participants who have histological diagnosis as peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL).
Participant who have measurable disease.
Participant who had previous systemic chemotherapy.
Participant who had disease progression (PD) or did not have response (complete response (CR) or partial response (PR)) in systemic chemotherapy, or relapsed or progressed after systemic chemotherapy.
Participant with Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.
Participant with adequate renal, liver and bone marrow function.
Male and female participants ≥20 years of age at the time of informed consent.
Participants who have provided written consent to participate in the study.

Exclusion Criteria:

Participant with serious complications or histories.
Participant with history of hypersensitivity to protein therapeutics.
Participant who is positive for Human immunodeficiency virus (HIV) antibody, Hepatitis C virus (HCV) antibody, or Hepatitis B Surface (HBs) antigen.
Participant with malignancy of activity other than PTCL or CTCL within 36 months before informed consent.
Women of childbearing potential or man of impregnate potential who don't agree to use a medically effective method for contraception.
Woman who is pregnant or lactating.
Participant with allogeneic stem cell transplantation.
Participant who were decided as inappropriate to participate in the study by the investigator or sub-investigator.

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

E7777

Arm Description

Participants with relapsed or refractory peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL) will receive 9 μg/kg/day of E7777, administered by intravenous drip infusion in 60 minutes (± 10 min) for Days 1 through 5 of each cycle in maximum of 8 cycles. Every cycle consists of 3 weeks.

Outcomes

Primary Outcome Measures

Objective Response Rate (ORR)

ORR was defined as the percentage of participants whose best overall response (BOR) was complete response (CR) or partial response (PR) based on independent review of Efficacy and Safety Evaluation Committee. ORR was assessed according to modified response criteria based on the revised response criteria for malignant lymphoma (Cheson, 2007), skin lesion and peripheral blood disease were assessed according to clinical end points and response criteria in mycosis fungoides and Sezary syndrome (Olsen, 2011). CR: Disappearance of all evidence of disease; PR: Regression of measurable disease and no new sites.

Secondary Outcome Measures

Progression Free Survival (PFS)

PFS: time between the date of administration of the first dose of the study drug and the date of the first documentation of progressive disease (PD) or death due to any cause (whichever occurred first) based on independent review of Efficacy and Safety Evaluation Committee, assessed by modified response criteria based on the revised response criteria for malignant lymphoma (Cheson, 2007), skin lesion and peripheral blood disease assessed according to clinical end points and response criteria in mycosis fungoides and Sezary syndrome (Olsen, 2011). PD: Any new lesion or unequivocally increase of previously involved sites from nadir. PFS was calculated using Kaplan-Meier method. Participants with no baseline assessments, treatment discontinuation without postbaseline tumor assessments, new anticancer treatment started prior to disease progression, death or PD after more than one missed tumor assessments and participants still on treatment without PD as of data cut-off were censored.

Duration of Response (DOR)

DOR: Time between date of first documentation of CR or PR and PD or death due to any cause based on independent review of Efficacy and Safety Evaluation Committee, assessed by modified response criteria based on revised response criteria for malignant lymphoma (Cheson,2007),skin lesion and peripheral blood disease by clinical end points and response criteria in mycosis fungoides and Sezary syndrome(Olsen,2011). DOR was assessed in responders who had CR or PR. CR: Disappearance of all evidence of disease; PR: Regression of measurable disease and no new sites. PD: Any new lesion or unequivocally increase of previously involved sites from nadir. DOR was calculated using Kaplan-Meier method. Participants with new anticancer treatment started prior to disease progression, death or PD after more than one missed tumor assessments and participants still on treatment without PD as of data cut-off were censored.

Time to Response (TTR)

TTR was defined as time between the date of administration of the first dose of the study drug and the date of first documentation PR or CR based on independent review of Efficacy and Safety Evaluation Committee. PR or CR were assessed according to modified response criteria based on the revised response criteria for malignant lymphoma (Cheson, 2007), skin lesion and peripheral blood disease were assessed according to clinical end points and response criteria in mycosis fungoides and Sezary syndrome (Olsen, 2011). TTR was only conducted among responders who had experienced CR or PR. CR: Disappearance of all evidence of disease; PR: Regression of measurable disease and no new sites.

CR Rate

CR rate was defined as the percentage of participants whose BOR was CR based on independent review of Efficacy and Safety Evaluation Committee. CR was assessed according to modified response criteria based on the revised response criteria for malignant lymphoma (Cheson, 2007), skin lesion and peripheral blood disease were assessed according to clinical end points and response criteria in mycosis fungoides and Sezary syndrome (Olsen, 2011). CR: Disappearance of all evidence of disease.

Overall Survival (OS)

OS was defined as the time between the date of administration of the first dose of the study drug and the date of death due to any cause. Participants who were alive at cut-off were censored.

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Cmax: Maximum Observed Serum Concentration for E7777

Tmax: Time to Reach the Cmax for E7777

AUC(0-t ): Area Under the Serum Concentration-time Curve From Time 0 to the Last Measurable Point for E7777

AUC(0-inf): Area Under the Serum Concentration-time Curve From Time 0 to Infinity for E7777

11 participants were included in the PK analysis, however AUC(0-inf), could not be estimated for 1 participant due to insufficient data for elimination rate constant.

Mean Residence Time (MRT) for E7777

11 participants were included in the PK analysis, however MRT, could not be estimated for 1 participant due to insufficient data for elimination rate constant.

t1/2: Terminal Elimination Phase Half-life for E7777

11 participants were included in the PK analysis, however t1/2, could not be estimated for 1 participant due to insufficient data for elimination rate constant.

CL: Total Clearance for E7777

11 participants were included in the PK analysis, however CL, could not be estimated for 1 participant due to insufficient data for elimination rate constant.

Vz: Volume of Distribution at Terminal Phase for E7777

11 participants were included in the PK analysis, however Vz, could not be estimated for 1 participant due to insufficient data for elimination rate constant.

Vss: Volume of Distribution at Steady State for E7777

11 participants were included in the PK analysis, however Vss, could not be estimated for 1 participant due to insufficient data for elimination rate constant.

Rac (Cmax): Accumulation Ratio of Cmax for E7777

Accumulation Ratio of Cmax was calculated as RAC (Cmax) on Cycle 3 Day 1 divided by RAC (Cmax) on Cycle 1 Day 1, and RAC (Cmax) on Cycle 5 Day 1 divided by RAC (Cmax) on Cycle 1 Day 1.

Rac (AUC): Accumulation Ratio of AUC for E7777

Accumulation ratio of AUC was calculated as RAC (AUC) on Cycle 3 Day 1 divided by RAC (AUC) on Cycle 1 Day 1, and RAC (AUC) on Cycle 5 Day 1 divided by RAC (AUC) on Cycle 1 Day 1.

Number of Participants With Positive Anti-E7777 and Anti-IL-2 Antibodies

Number of Participants With Positive Neutralizing Activity of Anti-E7777 Antibody

Full Information

NCT ID

NCT02676778

First Posted

February 4, 2016

Last Updated

June 24, 2021

Sponsor

Eisai Co., Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT02676778

Brief Title

Study of E7777 in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma and Cutaneous T-cell Lymphoma

Official Title

A Phase 2 Study of E7777 in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma and Cutaneous T-cell Lymphoma

Study Type

Interventional

2. Study Status

Record Verification Date

June 2021

Overall Recruitment Status

Completed

Study Start Date

March 28, 2016 (Actual)

Primary Completion Date

April 26, 2019 (Actual)

Study Completion Date

April 26, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eisai Co., Ltd.

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to evaluate the objective response rate (ORR) of E7777 in participants with relapsed or refractory peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL).

Detailed Description

This is a multicenter, single-arm, open label, Phase 2 to evaluate efficacy, safety, pharmacokinetics and immunogenicity of E7777 in participants with relapsed or refractory PTCL and CTCL.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Peripheral T-cell Lymphoma, Cutaneous T-cell Lymphoma

Keywords

Peripheral T-cell lymphoma, Cutaneous T-cell lymphoma, E7777, Phase 2

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

45 (Actual)

8. Arms, Groups, and Interventions

Arm Title

E7777

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

E7777

Primary Outcome Measure Information:

Title

Objective Response Rate (ORR)

Description

Time Frame

From the date of administration of the first dose of the study drug until completion of the study or treatment discontinuation, up to approximately 3 years 1 month

Secondary Outcome Measure Information:

Title

Progression Free Survival (PFS)

Description

Time Frame

From the date of administration of the first dose of the study drug until date of the first documentation of PD or death due to any cause (whichever occurred first) up to approximately 3 years 1 month

Title

Duration of Response (DOR)

Description

Time Frame

From the date of first documentation of CR or PR until date of the first documentation of PD or death due to any cause (whichever occurred first) up to approximately 3 years 1 month

Title

Time to Response (TTR)

Description

Time Frame

From the date of administration of the first dose of the study drug until date of the first documentation of PR or CR or death due to any cause (whichever occurred first) up to approximately 3 years 1 month

Title

CR Rate

Description

Time Frame

From the date of administration of the first dose of the study drug until completion of the study or treatment discontinuation, up to approximately 3 years 1 month

Title

Overall Survival (OS)

Description

OS was defined as the time between the date of administration of the first dose of the study drug and the date of death due to any cause. Participants who were alive at cut-off were censored.

Time Frame

From date of administration of the first dose of the study drug until the date of death due to any cause up to approximately 3 years 1 month

Title

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Time Frame

From the date of administration of the first dose of the study drug up to 30 days after the last dose of study drug (approximately up to 3 years 1 month)

Title

Cmax: Maximum Observed Serum Concentration for E7777

Time Frame