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A Trial of E7777 in Persistent and Recurrent Cutaneous T-Cell Lymphoma

Primary Purpose

Persistent or Recurrent Cutaneous T-Cell Lymphoma

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
E7777 9 mcg/kg
Sponsored by
Eisai Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Persistent or Recurrent Cutaneous T-Cell Lymphoma focused on measuring Persistent or Recurrent Cutaneous T-Cell Lymphoma, E7777

Eligibility Criteria

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

Inclusion Criteria:

Participants must meet all of the following criteria to be included in the study:

  1. Age greater than or equal to 18 years.
  2. Histopathologic diagnosis of CTCL (mycosis fungoides [MF] or Sezary Syndrome [SS]), confirmed by skin biopsy, or lymph node, or blood assessment, of current disease.
  3. CD25 assay-positive tumor, defined as detectable CD25 on greater than or equal to 20% of total lymphoid infiltrate in biopsied lesions by immunohistochemistry.
  4. CTCL disease stage at study entry as follows, according to ISCL/EORTC (Olsen 2011).

    • Lead-In Part: Stage IA - IV, except participants with CNS involvement.
    • Main Study: Stage I - III
  5. History of prior therapies for CTCL: must have had prior therapy, any number of prior therapies allowed.

    Topical treatments (except topical chemotherapy) and steroids are not considered as prior therapies.

  6. A minimum washout period of 4 weeks after previous CTCL therapy is recommended before the first dose of E7777.

    Participants must have recovered from any adverse effects from any previous CTCL therapy to Common Terminology Criteria for Adverse Events (CTCAE) Grade <2 before starting study drug. A shorter washout may be allowed if participant is experiencing progressive disease despite ongoing treatment.

  7. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 in the Lead-In Part and performance status of 0 or 1 in the Main Study.
  8. Life expectancy greater than or equal to 3 months in the Lead-In Part and greater than or equal to 12 months in the Main Study.
  9. Adequate bone marrow reserves as evidenced by:

    • platelets greater than or equal to 100,000/mm^3 (100 x 10^9/L)
    • clinically stable hemoglobin greater than or equal to 9 gram per deciliter (g/dL) (90 g/L) and hematocrit greater than or equal to 27% without transfusion support
  10. Normal hepatic function as evidenced by:

    • bilirubin <= 1.5* upper limit if normal (ULN) and alkaline phosphatase <=3.0*ULN
    • aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 3.0*ULN
    • albumin >= 3.0 g/dL (30 g/L)
  11. Adequate renal function as evidenced by serum creatinine less than or equal to 1.8 mg/dL (158 umol/L) or calculated creatinine clearance greater than or equal to 50 mL/min (per the Cockcroft-Gault formula) with less than 2+ protein or 24- hour urine creatinine clearance greater than or equal to 50 mL/minute with 24- hour urine protein less than 1gram.
  12. Provide written informed consent prior to any study-specific screening procedures.
  13. Females may not be lactating or pregnant at Screening or Baseline
  14. All females will be considered to be of childbearing potential unless they are postmenopausal or have been sterilized surgically
  15. Male participants must have had a successful vasectomy (confirmed azoospermia) or they and their female partner must meet the criteria above

Exclusion Criteria

Participants who meet any of the following criteria will be excluded from the study:

  1. Prior denileukin diftitox therapy
  2. Use of topical steroids within 14 days of Day 1 of initial therapy is not allowed.Topical steroids or systemic low dose steroids of less than or equal to 10 milligram per day (mg/day) prednisone are allowed in participants with erythroderma who have been on corticosteroids for a prolonged period of time and where discontinuation may lead to rebound flare in disease. The concomitant steroid medication is allowed as long as the type of steroid, route of administration, and steroid dose remain the same as what the participant had been receiving for a prolonged period of time.
  3. Active malignancy (except for CTCL, definitively treated basal or squamous cell carcinoma of the skin, and carcinoma in-situ of the cervix) within the past 24 months.
  4. Serious intercurrent illness
  5. Significant cardiac disease requiring ongoing treatment, including congestive heart failure (CHF), severe coronary artery disease (CAD), cardiomyopathy, uncontrolled cardiac arrhythmia, unstable angina pectoris, or myocardial infarction (MI)
  6. Significant pulmonary symptoms or disease
  7. History of uncontrolled seizure disorder or active central nervous system disease
  8. Major surgery within 2 weeks of study enrollment
  9. Significant or uncontrolled infections requiring systemic anti-infective therapy
  10. Known human immunodeficiency virus (HIV) infection; known active hepatitis B or hepatitis C infection
  11. Females who are pregnant (positive urine test) or breastfeeding
  12. Any history of a medical condition or a concomitant medical condition that, in the opinion of the investigator, would compromise the participant's ability to safely complete the study.

Sites / Locations

  • University of Alabama at Birmingham, Dermatology at Whitaker Clinic
  • University of Arkansas for Medical Sciences
  • City of Hope Medical Center National Medical Center
  • UC Irvine Health-Chao Family Comprehensive Cancer Center
  • Stanford University Cancer Center
  • Yale University Cancer Center
  • University of Florida
  • H. Lee Moffitt Cancer Center
  • University of South Florida College of Medicine
  • Winship Cancer Institute of Emory University
  • Northwestern Memorial Hospital
  • Rush University Medical Center
  • Dana Farber Cancer Institute
  • Hackensack University Medical Center
  • Columbia University Medical Center
  • University of PittsburghMedical Center Presbyterian Shadyside
  • University of Pittsburgh Medical Center
  • The University of TX MD Anderson Cancer Center
  • Westmead Hospital
  • Epworth Healthcare Freemasons
  • Peter MacCallum Cancer Institute
  • Auxilio Mutuo Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

E7777

Arm Description

Outcomes

Primary Outcome Measures

Dose-limiting toxicities (DLTs) in the Lead-In Part
Maximum Tolerated Dose (MTD) in the Lead-In Part
ORR in the Main study

Secondary Outcome Measures

Duration of Response (DOR)
Time to Response (TTR)
ORR
Number of Participants with Any Adverse Event and Any Serious Adverse Event (SAE)
Maximum Drug Concentration (Cmax)
Area Under the Curve from Time 0 to Time t (AUC[0-t])
Area Under the Curve from Time 0 to Time Infinity (AUC[0-inf])
Terminal Elimination Half-life (t1/2)
Time to Reach Maximum (peak) Concentration After Drug Administration (Tmax)
Total Body Clearance (CL)
Volume of Distribution at Steady State (Vdss)
Percentage of Participants Testing Positive for Anti-E7777 and Anti-IL-2 Antibodies
Number of Participants with Skin Response in the Main Study
Duration of Skin Response in the Main Study
Time to Skin Response in the Main Study

Full Information

First Posted
March 28, 2013
Last Updated
December 5, 2022
Sponsor
Eisai Inc.
Collaborators
Dr. Reddy's Laboratory, Citius Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01871727
Brief Title
A Trial of E7777 in Persistent and Recurrent Cutaneous T-Cell Lymphoma
Official Title
A Clinical Study to Demonstrate Safety and Efficacy of E7777 in Persistent or Recurrent Cutaneous T-Cell Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
May 30, 2013 (Actual)
Primary Completion Date
December 6, 2021 (Actual)
Study Completion Date
December 14, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eisai Inc.
Collaborators
Dr. Reddy's Laboratory, Citius Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this trial is to assess the efficacy of E7777 in participants with recurrent or persistent Cutaneous T-Cell Lymphoma (CTCL) in Stage I - III participants as assessed by objective response rate (ORR). A lead-in dose-finding part was used to determine dose level 9 microgram per kilogram (mcg/kg) E7777 that is being used to test efficacy and safety.
Detailed Description
This is a multicenter, open-label study of E7777 in participants with recurrent or persistent CTCL. The study consists of an initial Lead-in part (to select recommended dose of E7777 for Main part), followed by the Main part (to test efficacy). Participants will move through three phases while on study: Pretreatment Phase, Treatment Phase, and Extension Phase and a Follow-up Period.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Persistent or Recurrent Cutaneous T-Cell Lymphoma
Keywords
Persistent or Recurrent Cutaneous T-Cell Lymphoma, E7777

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
112 (Actual)

8. Arms, Groups, and Interventions

Arm Title
E7777
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
E7777 9 mcg/kg
Intervention Description
administered by intravenous (i.v.) infusion over 60 minutes (+/-10 minutes) on 5 consecutive days during every cycle of 21 days
Primary Outcome Measure Information:
Title
Dose-limiting toxicities (DLTs) in the Lead-In Part
Time Frame
Cycle 1 (21 days)
Title
Maximum Tolerated Dose (MTD) in the Lead-In Part
Time Frame
Up to12 months
Title
ORR in the Main study
Time Frame
Day 1 until disease progression/recurrence, or up to 30 months
Secondary Outcome Measure Information:
Title
Duration of Response (DOR)
Time Frame
Day 1 until disease progression/recurrence, or up to 12 months (Lead-in Part) and Day 1 until disease progression/recurrence, or up to 30 months (Main Study)
Title
Time to Response (TTR)
Time Frame
Up to 12 months (Lead-In Part) and up to 30 months (Main study)
Title
ORR
Time Frame
Day 1 until disease progression/recurrence, up to 12 months (Lead-in Part) and Day 1 until disease progression/recurrence, up to 30 months (by using Prince (2010) criteria in Main Study)
Title
Number of Participants with Any Adverse Event and Any Serious Adverse Event (SAE)
Time Frame
From first dose of the study drug until 30 days after the last dose, or up to 30 months
Title
Maximum Drug Concentration (Cmax)
Time Frame
Cycles 1, 3, 5 Day 1: pre-dose-300 minutes post infusion stop (Lead-in part and for first 12 participants in the Main study) (Cycle length is equal to [=] 21 days)
Title
Area Under the Curve from Time 0 to Time t (AUC[0-t])
Time Frame
Cycles 1, 3, 5 Day 1: pre-dose-300 minutes post infusion stop (Lead-in part and for first 12 participants in the Main study) (Cycle length=21 days)
Title
Area Under the Curve from Time 0 to Time Infinity (AUC[0-inf])
Time Frame
Cycles 1, 3, 5 Day 1: pre-dose-300 minutes post infusion stop (Lead-in part and for first 12 participants in the Main study) (Cycle length=21 days)
Title
Terminal Elimination Half-life (t1/2)
Time Frame
Cycles 1, 3, 5 Day 1: pre-dose-300 minutes post infusion stop (Lead-in part and for first 12 participants in the Main study) (Cycle length=21 days)
Title
Time to Reach Maximum (peak) Concentration After Drug Administration (Tmax)
Time Frame
Cycles 1, 3, 5 Day 1: pre-dose-300 minutes post infusion stop (Lead-in part and for first 12 participants in the Main study) (Cycle length=21 days)
Title
Total Body Clearance (CL)
Time Frame
Cycles 1, 3, 5 Day 1: pre-dose-300 minutes post infusion stop (Lead-in part and for first 12 participants in the Main study) (Cycle length=21 days)
Title
Volume of Distribution at Steady State (Vdss)
Time Frame
Cycles 1, 3, 5 Day 1: pre-dose-300 minutes post infusion stop (Lead-in part and for first 12 participants in the Main study) (Cycle length=21 days)
Title
Percentage of Participants Testing Positive for Anti-E7777 and Anti-IL-2 Antibodies
Time Frame
Da y 1 of Cycles 1, 2, 3, 5, and 8 (for Anti-E7777 and Anti-IL-2); Anti-IL-2 is to be tested at 6 month, 1 year, and thereafter every year until antibody levels decrease to baseline levels
Title
Number of Participants with Skin Response in the Main Study
Time Frame
Day 1 until disease progression/recurrence, or up to 30 months
Title
Duration of Skin Response in the Main Study
Time Frame
Day 1 until disease progression/recurrence, or up to 30 months
Title
Time to Skin Response in the Main Study
Time Frame
Up to 30 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participants must meet all of the following criteria to be included in the study: Age greater than or equal to 18 years. Histopathologic diagnosis of CTCL (mycosis fungoides [MF] or Sezary Syndrome [SS]), confirmed by skin biopsy, or lymph node, or blood assessment, of current disease. CD25 assay-positive tumor, defined as detectable CD25 on greater than or equal to 20% of total lymphoid infiltrate in biopsied lesions by immunohistochemistry. CTCL disease stage at study entry as follows, according to ISCL/EORTC (Olsen 2011). Lead-In Part: Stage IA - IV, except participants with CNS involvement. Main Study: Stage I - III History of prior therapies for CTCL: must have had prior therapy, any number of prior therapies allowed. Topical treatments (except topical chemotherapy) and steroids are not considered as prior therapies. A minimum washout period of 4 weeks after previous CTCL therapy is recommended before the first dose of E7777. Participants must have recovered from any adverse effects from any previous CTCL therapy to Common Terminology Criteria for Adverse Events (CTCAE) Grade <2 before starting study drug. A shorter washout may be allowed if participant is experiencing progressive disease despite ongoing treatment. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 in the Lead-In Part and performance status of 0 or 1 in the Main Study. Life expectancy greater than or equal to 3 months in the Lead-In Part and greater than or equal to 12 months in the Main Study. Adequate bone marrow reserves as evidenced by: platelets greater than or equal to 100,000/mm^3 (100 x 10^9/L) clinically stable hemoglobin greater than or equal to 9 gram per deciliter (g/dL) (90 g/L) and hematocrit greater than or equal to 27% without transfusion support Normal hepatic function as evidenced by: bilirubin <= 1.5* upper limit if normal (ULN) and alkaline phosphatase <=3.0*ULN aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 3.0*ULN albumin >= 3.0 g/dL (30 g/L) Adequate renal function as evidenced by serum creatinine less than or equal to 1.8 mg/dL (158 umol/L) or calculated creatinine clearance greater than or equal to 50 mL/min (per the Cockcroft-Gault formula) with less than 2+ protein or 24- hour urine creatinine clearance greater than or equal to 50 mL/minute with 24- hour urine protein less than 1gram. Provide written informed consent prior to any study-specific screening procedures. Females may not be lactating or pregnant at Screening or Baseline All females will be considered to be of childbearing potential unless they are postmenopausal or have been sterilized surgically Male participants must have had a successful vasectomy (confirmed azoospermia) or they and their female partner must meet the criteria above Exclusion Criteria Participants who meet any of the following criteria will be excluded from the study: Prior denileukin diftitox therapy Use of topical steroids within 14 days of Day 1 of initial therapy is not allowed.Topical steroids or systemic low dose steroids of less than or equal to 10 milligram per day (mg/day) prednisone are allowed in participants with erythroderma who have been on corticosteroids for a prolonged period of time and where discontinuation may lead to rebound flare in disease. The concomitant steroid medication is allowed as long as the type of steroid, route of administration, and steroid dose remain the same as what the participant had been receiving for a prolonged period of time. Active malignancy (except for CTCL, definitively treated basal or squamous cell carcinoma of the skin, and carcinoma in-situ of the cervix) within the past 24 months. Serious intercurrent illness Significant cardiac disease requiring ongoing treatment, including congestive heart failure (CHF), severe coronary artery disease (CAD), cardiomyopathy, uncontrolled cardiac arrhythmia, unstable angina pectoris, or myocardial infarction (MI) Significant pulmonary symptoms or disease History of uncontrolled seizure disorder or active central nervous system disease Major surgery within 2 weeks of study enrollment Significant or uncontrolled infections requiring systemic anti-infective therapy Known human immunodeficiency virus (HIV) infection; known active hepatitis B or hepatitis C infection Females who are pregnant (positive urine test) or breastfeeding Any history of a medical condition or a concomitant medical condition that, in the opinion of the investigator, would compromise the participant's ability to safely complete the study.
Facility Information:
Facility Name
University of Alabama at Birmingham, Dermatology at Whitaker Clinic
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
University of Arkansas for Medical Sciences
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
City of Hope Medical Center National Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
UC Irvine Health-Chao Family Comprehensive Cancer Center
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Stanford University Cancer Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Yale University Cancer Center
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
H. Lee Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
University of South Florida College of Medicine
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Winship Cancer Institute of Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Northwestern Memorial Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
University of PittsburghMedical Center Presbyterian Shadyside
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15219
Country
United States
Facility Name
The University of TX MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Westmead Hospital
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Epworth Healthcare Freemasons
City
East Melbourne
State/Province
Victoria
ZIP/Postal Code
3002
Country
Australia
Facility Name
Peter MacCallum Cancer Institute
City
East Melbourne
State/Province
Victoria
ZIP/Postal Code
3002
Country
Australia
Facility Name
Auxilio Mutuo Cancer Center
City
San Juan
ZIP/Postal Code
00918
Country
Puerto Rico

12. IPD Sharing Statement

Learn more about this trial

A Trial of E7777 in Persistent and Recurrent Cutaneous T-Cell Lymphoma

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