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

NCT ID: NCT01871727

Last Updated: 2024-11-13

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

112 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-05-30

Study Completion Date

2021-12-14

Brief Summary

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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

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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.

Conditions

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Persistent or Recurrent Cutaneous T-Cell Lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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E7777

Group Type EXPERIMENTAL

E7777 9 mcg/kg

Intervention Type DRUG

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

Interventions

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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

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Dr. Reddy's Laboratories Limited

INDUSTRY

Sponsor Role collaborator

Citius Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role collaborator

Eisai Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Alabama at Birmingham, Dermatology at Whitaker Clinic

Birmingham, Alabama, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

City of Hope Medical Center National Medical Center

Duarte, California, United States

Site Status

UC Irvine Health-Chao Family Comprehensive Cancer Center

Orange, California, United States

Site Status

Stanford University Cancer Center

Stanford, California, United States

Site Status

Yale University Cancer Center

New Haven, Connecticut, United States

Site Status

University of Florida

Gainesville, Florida, United States

Site Status

H. Lee Moffitt Cancer Center

Tampa, Florida, United States

Site Status

University of South Florida College of Medicine

Tampa, Florida, United States

Site Status

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Site Status

Northwestern Memorial Hospital

Chicago, Illinois, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

University of PittsburghMedical Center Presbyterian Shadyside

Pittsburgh, Pennsylvania, United States

Site Status

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

The University of TX MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Westmead Hospital

Westmead, New South Wales, Australia

Site Status

Epworth Healthcare Freemasons

East Melbourne, Victoria, Australia

Site Status

Peter MacCallum Cancer Institute

East Melbourne, Victoria, Australia

Site Status

Auxilio Mutuo Cancer Center

San Juan, , Puerto Rico

Site Status

Countries

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United States Australia Puerto Rico

References

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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.

Reference Type DERIVED
PMID: 39700456 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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E7777-G000-302

Identifier Type: -

Identifier Source: org_study_id

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