Clinical trial NCT01871727: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Persistent or Recurrent Cutaneous T-Cell Lymphoma
Keywords: Persistent or Recurrent Cutaneous T-Cell Lymphoma
E7777
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
Collaborators: name: Dr. Reddy's Laboratories Limited
name: Citius Pharmaceuticals, Inc.
First posted: 2013-06-07
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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)
timeFrame: Cycle 1 (cycle length was 21 days)
measure: Lead-In Part: Maximum Tolerated Dose (MTD) of E7777
timeFrame: Cycle 1 (cycle length was 21 days)
measure: Main Study Part: Objective Response Rate (ORR) by Independent Review Committee (IRC) Based on Olsen 2011 Criteria
timeFrame: From the date of administration of the first dose of the study drug until disease progression (Up to 3 years 6 months)
Secondary outcomes:
measure: Lead-In Part: Duration of Response (DOR) Per Investigator Assessment
timeFrame: 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)
measure: Main Study Part: Duration of Response (DOR) Per Independent Review Committee
timeFrame: 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)
measure: Lead-In Part: Time to Response (TTR) Per Investigator Assessment
timeFrame: 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)
measure: Main Study Part: Time to Response (TTR) Per Independent Review Committee
timeFrame: 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)
measure: Lead-In Part and Main Study Part: ORR Per Investigator Assessment
timeFrame: From the date of administration of the first dose of the study drug until disease progression (Up to 3 years 6 months)
measure: Main Study Part: ORR Per IRC Based on Prince 2010 Criteria
timeFrame: From the date of administration of the first dose of the study drug until disease progression (Up to 3 years 6 months)
measure: Lead-In Part and Main Study Part: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: From the first dose of study drug up to 30 days after the last dose (Up to 3 years and 7 months)
measure: Lead-In Part: Maximum Serum Concentration (Cmax) of E7777
timeFrame: Cycles 1, 3, 5 Day 1: Pre-dose up to 300 minutes post-dose (Cycle length was 21 days)
measure: Main Study Part: Maximum Serum Concentration (Cmax) of E7777
timeFrame: Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 minutes post-dose (Cycle length was 21 days)
measure: Lead-In Part: Area Under the Curve From Time 0 to Time t (AUC[0-t]) of E7777
timeFrame: Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours Post-dose (Cycle length was 21 days)
measure: Main Study Part: Area Under the Curve From Time 0 to Time t (AUC[0-t]) of E7777
timeFrame: Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
measure: Lead-In Part: Area Under the Curve From Time 0 to Time Infinity (AUC[0-inf]) of E7777
timeFrame: Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
measure: Main Study Part: Area Under the Curve From Time 0 to Time Infinity (AUC[0-inf]) of E7777
timeFrame: Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
measure: Lead-In Part: Terminal Elimination Half-life (t1/2) of E7777
timeFrame: Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
measure: Main Study Part: Terminal Elimination Half-life (t1/2) of E7777
timeFrame: Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
measure: Lead-In Part: Time to Reach Maximum (Peak) Concentration After Drug Administration (Tmax)
timeFrame: Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
measure: Main Study Part: Time to Reach Maximum (Peak) Concentration After Drug Administration (Tmax)
timeFrame: Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
measure: Lead-In Part: Total Body Clearance (CL) of E7777
timeFrame: Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
measure: Main Study Part: Total Body Clearance (CL) of E7777
timeFrame: Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
measure: Lead-In Part: Volume of Distribution at Steady State (Vdss) of E7777
timeFrame: Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
measure: Main Study Part: Volume of Distribution at Steady State (Vdss) of E7777
timeFrame: Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
measure: Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies
timeFrame: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 5 Day 1
measure: Main Study Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-IL-2 Antibodies
timeFrame: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1
measure: Main Study Part: Number of Participants With Objective Skin Response
timeFrame: Up to 30 months
measure: Main Study Part: Duration of Skin Response
timeFrame: Up to 30 months
measure: Main Study Part: Time to Skin Response
timeFrame: Up to 30 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham, Dermatology at Whitaker Clinic
state: Alabama
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Duarte
country: United States
facility: City of Hope Medical Center National Medical Center
state: California
city: Orange
country: United States
facility: UC Irvine Health-Chao Family Comprehensive Cancer Center
state: California
city: Stanford
country: United States
facility: Stanford University Cancer Center
state: California
city: New Haven
country: United States
facility: Yale University Cancer Center
state: Connecticut
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Tampa
country: United States
facility: University of South Florida College of Medicine
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Pittsburgh
country: United States
facility: University of PittsburghMedical Center Presbyterian Shadyside
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Houston
country: United States
facility: The University of TX MD Anderson Cancer Center
state: Texas
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: East Melbourne
country: Australia
facility: Epworth Healthcare Freemasons
state: Victoria
city: East Melbourne
country: Australia
facility: Peter MacCallum Cancer Institute
state: Victoria
city: San Juan
country: Puerto Rico
facility: Auxilio Mutuo Cancer Center
Study officials:
References: