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

NCT01871727 | Completed Phase 3 Results

• 1 other identifier: E7777-G000-302
• Study Type: interventional
• Target: 112
• Locations: 3 countries
• Sites: 22

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.

Conditions

Persistent or Recurrent Cutaneous T-Cell Lymphoma

Keywords

Persistent or Recurrent Cutaneous T-Cell Lymphoma; E7777

Outcome Measures

Primary Outcomes (3)

• Lead-In Part: Number of Participants With Dose-limiting Toxicities (DLTs) as Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03)

  DLTs as per NCI CTCAE v4.03 were defined as 1) serious infusion reaction (CTCAE) Grade 4 adverse event of "Infusion related reaction," or recurrent CTCAE Grade 3 despite administration of systemic steroid premedication after initial occurrence. Infusion reactions were defined as symptoms (example, fatigue, nausea, vomiting, arthralgia, myalgia, pyrexia, chills, rigors) occurring within 24 hours of E7777 infusion. 2) Capillary leak syndrome (CLS) CTCAE Grade 4 or Grade 3 (with exceptions). A CLS event was defined as the noted occurrence of at least 2 of the following: hypotension, edema, or serum albumin less than (\<) 3.0 gram per decilitre (g/dL). 3) Clinical visual impairment. 4) Any CTCAE Grade greater than or equal to (\>=) 4 adverse event (AE) that may represent an infusion reaction. 5) Any other Grade 3 or greater toxicity assessed as related to E7777 treatment and which in the opinion of a safety consultancy investigator panel, was a dose-limiting toxicity.

  Cycle 1 (cycle length was 21 days)

• Lead-In Part: Maximum Tolerated Dose (MTD) of E7777

  The MTD was defined as the safe dose level established in Lead-In Part. MTD was determined by summarizing the number and percentage of participants with DLTs for the first cycle, by study dosing schedule, initial dosing level and overall for the Lead-In Part.

  Cycle 1 (cycle length was 21 days)

• Main Study Part: Objective Response Rate (ORR) by Independent Review Committee (IRC) Based on Olsen 2011 Criteria

  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 committee on 2 assessments at least 3 weeks apart. The tumor response was based on global response score (GRS) Olsen 2011 criteria. CR was defined as disappearance of all evidence of disease and PR was defined as regression of measurable disease and no new sites.

  From the date of administration of the first dose of the study drug until disease progression (Up to 3 years 6 months)

Secondary Outcomes (26)

• Lead-In Part: Duration of Response (DOR) Per Investigator Assessment

  From the date of first documentation of CR or PR until date of the first documentation of PD or death due to any cause (Up to 1 year 2 months)

• Main Study Part: Duration of Response (DOR) Per Independent Review Committee

  From the date of first documentation of CR or PR until date of the first documentation of PD or death due to any cause (Up to 3 years 6 months)

• Lead-In Part: Time to Response (TTR) Per Investigator Assessment

  From the date of administration of the first dose of the study drug until date of the first documentation of PR or CR (Up to 1 year 2 months)

• Main Study Part: Time to Response (TTR) Per Independent Review Committee

  From the date of administration of the first dose of the study drug until date of the first documentation of PR or CR (Up to 3 years 6 months)

• Lead-In Part and Main Study Part: ORR Per Investigator Assessment

  From the date of administration of the first dose of the study drug until disease progression (Up to 3 years 6 months)

Study Arms (1)

E7777

EXPERIMENTAL

Drug: E7777 9 mcg/kg

Interventions

E7777 9 mcg/kg DRUG

administered by intravenous (i.v.) infusion over 60 minutes (+/-10 minutes) on 5 consecutive days during every cycle of 21 days

E7777

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eisai Inc.: lead
• Dr. Reddy's Laboratories Limited: collaborator
• Citius Pharmaceuticals, Inc.: collaborator

Study Sites (22)

University of Alabama at Birmingham, Dermatology at Whitaker Clinic

Birmingham, Alabama, 35233, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

City of Hope Medical Center National Medical Center

Duarte, California, 91010, United States

Location

UC Irvine Health-Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

Stanford University Cancer Center

Stanford, California, 94305, United States

Location

Yale University Cancer Center

New Haven, Connecticut, 06520, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

H. Lee Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of South Florida College of Medicine

Tampa, Florida, 33612, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60612, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University of PittsburghMedical Center Presbyterian Shadyside

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15219, United States

Location

The University of TX MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Epworth Healthcare Freemasons

East Melbourne, Victoria, 3002, Australia

Location

Peter MacCallum Cancer Institute

East Melbourne, Victoria, 3002, Australia

Location

Auxilio Mutuo Cancer Center

San Juan, 00918, Puerto Rico

Location

Related Publications (1)

• Foss FM, Kim YH, Prince HM, Akilov OE, Querfeld C, Seminario-Vidal L, Fisher DC, Kuzel TM, Yannakou CK, Geskin LJ, Feldman T, Sokol L, Allen PB, Dang NH, Cabanillas F, Wong HK, Ooi CE, Xing D, Sauter N, Singh P, Czuczman M, Duvic M. Efficacy and Safety of Denileukin Diftitox-Cxdl, an Improved Purity Formulation of Denileukin Diftitox, in Patients With Relapsed or Refractory Cutaneous T-Cell Lymphoma. J Clin Oncol. 2025 Apr;43(10):1198-1209. doi: 10.1200/JCO-24-01549. Epub 2024 Dec 19.

  PMID: 39700456 DERIVED

MeSH Terms

Conditions

Lymphoma, T-Cell, Cutaneous

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Eisai Medical Information
• Organization: Eisai Inc.

esi_oncmedinfo@eisai.com

1-888-274-2378

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2013
• First Posted: June 7, 2013
• Study Start: May 30, 2013
• Primary Completion: December 6, 2021
• Study Completion: December 14, 2021
• Last Updated: November 13, 2024
• Results First Posted: November 13, 2024

Record last verified: 2022-11

Locations

US (18); PR (1); AU (3)