The purpose of this trial is to assess the efficacy and safety of E7777 (improved purity
ONTAK) in patients with persistent and recurrent cutaneous T-cell lymphoma. 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.
This is a multicenter, open-label, single-arm study of E7777 in participants with recurrent
or persistent Cutaneous T-Cell Lymphoma (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). Lead in part is complete and main study is ongoing. Participants will move through
three phases while on study: Pretreatment Phase, Treatment Phase, and Extension Phase and a
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 IA - IVA2 including lymph node disease N2 and N3
5. History of prior therapies for CTCL as follows: must have had prior therapy, any
number of prior therapies allowed.
Topical treatments (except topical chemotherapy) and steroids are not considered as
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/mm3 (100 x 10^9/L)
- clinically stable hemoglobin greater than or equal to 9 g/dL (90 g/L) and
hematocrit greater than or equal to 27% without transfusion support
10. Normal hepatic function as evidenced by:
- bilirubin and alkaline phosphatase less than or equal to 1 x the upper limit of
- aspartate aminotransferase (AST) less than or equal to 75 U/L and alanine
aminotransferase (ALT) less than or equal to 100 U/L.
- albumin greater than or equal to 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 1g.
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
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.