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

A Clinical Study to Demonstrate Safety and Efficacy of E7777 in Persistent or Recurrent Cutaneous T-Cell Lymphoma

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.

Study Overview

• Status: Completed
• Conditions: Persistent or Recurrent Cutaneous T-Cell Lymphoma
• Intervention / Treatment: Drug: E7777 9 mcg/kg

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.

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
      • Peter Maccallum Cancer Institute
    • East Melbourne, Victoria, Australia, 3002
      • Epworth Healthcare Freemasons
• Puerto Rico
  • San Juan, Puerto Rico, 00918
    • Auxilio Mutuo Cancer Center
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham, Dermatology at Whitaker Clinic
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Duarte, California, United States, 91010
      • City of Hope Medical Center National Medical Center
    • Orange, California, United States, 92868
      • UC Irvine Health-Chao Family Comprehensive Cancer Center
    • Stanford, California, United States, 94305
      • Stanford University Cancer Center
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University Cancer Center
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center
    • Tampa, Florida, United States, 33612
      • University of South Florida College of Medicine
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute of Emory University
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60612
      • Northwestern Memorial Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15219
      • University of Pittsburgh Medical Center
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of PittsburghMedical Center Presbyterian Shadyside
  • Texas
    • Houston, Texas, United States, 77030
      • The University of TX MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: E7777	Drug: E7777 9 mcg/kg; administered by intravenous (i.v.) infusion over 60 minutes (+/-10 minutes) on 5 consecutive days during every cycle of 21 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Dose-limiting toxicities (DLTs) in the Lead-In Part	Cycle 1 (21 days)
Maximum Tolerated Dose (MTD) in the Lead-In Part	Up to12 months
ORR in the Main study	Day 1 until disease progression/recurrence, or up to 30 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of Response (DOR)	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)
Time to Response (TTR)	Up to 12 months (Lead-In Part) and up to 30 months (Main study)
ORR	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)
Number of Participants with Any Adverse Event and Any Serious Adverse Event (SAE)	From first dose of the study drug until 30 days after the last dose, or up to 30 months
Maximum Drug Concentration (Cmax)	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)
Area Under the Curve from Time 0 to Time t (AUC[0-t])	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)
Area Under the Curve from Time 0 to Time Infinity (AUC[0-inf])	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)
Terminal Elimination Half-life (t1/2)	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)
Time to Reach Maximum (peak) Concentration After Drug Administration (Tmax)	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)
Total Body Clearance (CL)	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)
Volume of Distribution at Steady State (Vdss)	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)
Percentage of Participants Testing Positive for Anti-E7777 and Anti-IL-2 Antibodies	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
Number of Participants with Skin Response in the Main Study	Day 1 until disease progression/recurrence, or up to 30 months
Duration of Skin Response in the Main Study	Day 1 until disease progression/recurrence, or up to 30 months
Time to Skin Response in the Main Study	Up to 30 months

Collaborators and Investigators

• Sponsor: Eisai Inc.
• Collaborators: Dr. Reddy's Laboratory; Citius Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2013
• Primary Completion (Actual): December 6, 2021
• Study Completion (Actual): December 14, 2021

Study Registration Dates

• First Submitted: March 28, 2013
• First Submitted That Met QC Criteria: June 4, 2013
• First Posted (Estimate): June 7, 2013

Study Record Updates

• Last Update Posted (Estimate): December 12, 2022
• Last Update Submitted That Met QC Criteria: December 5, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Persistent or Recurrent Cutaneous T-Cell Lymphoma; E7777
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Disease Attributes; Lymphoma; Recurrence; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous
• Other Study ID Numbers: E7777-G000-302