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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Peripheral T-cell Lymphoma, Cutaneous T-cell Lymphoma

Intervention / Treatment
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* Drug: E7777


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: E7777<br>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. | Drug: E7777<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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 Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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 | 
| 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. | 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 | 
| 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. | 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 | 
| 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. | 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 | 
| 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. | 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 | 
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |  | 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) | 
| Cmax: Maximum Observed Serum Concentration for E7777 |  | Cycle 1 Day 1: 0-240 minutes post-infusion; Cycle 3 and 5 Day 1: 0-120 minutes post-infusion (each Cycle length = 3 weeks) | 
| Tmax: Time to Reach the Cmax for E7777 |  | Cycle 1 Day 1: 0-240 minutes post-infusion; Cycle 3 and 5 Day 1: 0-120 minutes post-infusion (each Cycle length = 3 weeks) | 
| AUC(0-t ): Area Under the Serum Concentration-time Curve From Time 0 to the Last Measurable Point for E7777 |  | Cycle 1 Day 1: 0-240 minutes post-infusion; Cycle 3 and 5 Day 1: 0-120 minutes post-infusion (each Cycle length = 3 weeks) | 
| 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. | Cycle 1 Day 1: 0-240 minutes post-infusion; Cycle 3 and 5 Day 1: 0-120 minutes post-infusion (each Cycle length = 3 weeks) | 
| 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. | Cycle 1 Day 1: 0-240 minutes post-infusion; Cycle 3 and 5 Day 1: 0-120 minutes post-infusion (each Cycle length = 3 weeks) | 
| 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. | Cycle 1 Day 1: 0-240 minutes post-infusion; Cycle 3 and 5 Day 1: 0-120 minutes post-infusion (each Cycle length = 3 weeks) | 
| 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. | Cycle 1 Day 1: 0-240 minutes post-infusion; Cycle 3 and 5 Day 1: 0-120 minutes post-infusion (each Cycle length = 3 weeks) | 
| 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. | Cycle 1 Day 1: 0-240 minutes post-infusion; Cycle 3 and 5 Day 1: 0-120 minutes post-infusion (each Cycle length = 3 weeks) | 
| 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. | Cycle 1 Day 1: 0-240 minutes post-infusion; Cycle 3 and 5 Day 1: 0-120 minutes post-infusion (each Cycle length = 3 weeks) | 
| 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. | Cycle 1 Day 1: 0-240 minutes post-infusion; Cycle 3 and 5 Day 1: 0-120 minutes post-infusion (each Cycle length = 3 weeks) | 
| 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. | Cycle 1 Day 1: 0-240 minutes post-infusion; Cycle 3 and 5 Day 1: 0-120 minutes post-infusion (each Cycle length = 3 weeks) | 
| Number of Participants With Positive Anti-E7777 and Anti-IL-2 Antibodies |  | Cycles 1, 2, 3, 5, 8: Day 1 pre-dose; at treatment discontinuation or completion (Cycle 8 Day 21) (each Cycle length = 3 weeks) | 
| Number of Participants With Positive Neutralizing Activity of Anti-E7777 Antibody |  | Cycles 1, 2, 3, 5, 8: Day 1 pre-dose; at treatment discontinuation or completion (Cycle 8 Day 21) (each Cycle length = 3 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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E7777, Phase 2, Peripheral T-cell lymphoma, Cutaneous T-cell lymphoma