Persistent or Recurrent Cutaneous T-Cell LymphomaPhase 3NCT01871727
A Trial of E7777 in Persistent and Recurrent Cutaneous T-Cell Lymphoma
A Phase 3 study testing E7777 9 mcg/kg in people with Persistent or Recurrent Cutaneous T-Cell Lymphoma, run by Eisai Inc. at 22 sites in 3 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Persistent or Recurrent Cutaneous T-Cell Lymphoma
- What is being tested?
- E7777 9 mcg/kg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 112 participants
- Where
- 22 sitesin 3 countries
- Study dates
- 30 May 2013to 14 Dec 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 25Show fewer
- 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)
- 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
- 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)
- 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.
- Provide written informed consent prior to any study-specific screening procedures.
- Females may not be lactating or pregnant at Screening or Baseline
- All females will be considered to be of childbearing potential unless they are postmenopausal or have been sterilized surgically
- Male participants must have had a successful vasectomy (confirmed azoospermia) or they and their female partner must meet the criteria above
Who cannot join
- 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)
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- 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.
Trial locations and contacts
22 sites in 3 countries.
22 sites in 3 countries
United States18 sites
Winship Cancer Institute of Emory University
Atlanta, Georgia, 30322
University of Alabama at Birmingham, Dermatology at Whitaker Clinic
Birmingham, Alabama, 35233
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Northwestern Memorial Hospital
Chicago, Illinois, 60612
Rush University Medical Center
Chicago, Illinois, 60612
City of Hope Medical Center National Medical Center
Duarte, California, 91010
University of Florida
Gainesville, Florida, 32610
Hackensack University Medical Center
Hackensack, New Jersey, 07601
The University of TX MD Anderson Cancer Center
Houston, Texas, 77030
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Yale University Cancer Center
New Haven, Connecticut, 06520
Columbia University Medical Center
New York, New York, 10032
UC Irvine Health-Chao Family Comprehensive Cancer Center
Orange, California, 92868
University of PittsburghMedical Center Presbyterian Shadyside
Pittsburgh, Pennsylvania, 15213
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15219
Stanford University Cancer Center
Stanford, California, 94305
H. Lee Moffitt Cancer Center
Tampa, Florida, 33612
University of South Florida College of Medicine
Tampa, Florida, 33612
Australia3 sites
Epworth Healthcare Freemasons
East Melbourne, Victoria, 3002
Peter MacCallum Cancer Institute
East Melbourne, Victoria, 3002
Westmead Hospital
Westmead, New South Wales, 2145
About this study
Official title: 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.
Read the 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.
- Being tested
- E7777 9 mcg/kg
- Keywords
- Persistent or Recurrent Cutaneous T-Cell Lymphoma, E7777
- Medical subject headings
- Lymphoma, T-Cell, Cutaneous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
E7777 9 mcg/kgDrug
administered by intravenous (i.v.) infusion over 60 minutes (+/-10 minutes) on 5 consecutive days during every cycle of 21 days
| Study group | Role | What they receive |
|---|---|---|
| E7777 | Experimental | Not described Receives: Drug: E7777 9 mcg/kg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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
DOR per investigator assessment was defined as the time from date when criteria for response (CR or PR) was first met until the date of the first documentation of disease progression (PD) or date of death from any cause. The tumor assessment was based on 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. PD was defined as any new lesion or unequivocally increase of previously involved sites from nadir.
Measured: 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
DOR per independent review committee was defined as the time from the date when criteria for response (CR or PR) was first met until the date of the first documentation of PD or date of death from any cause. The tumor assessment was based on 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. PD was defined as any new lesion or unequivocally increase of previously involved sites from nadir.
Measured: 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
Time to response per investigator assessment was defined as the time from date of first dose to the date of the first documented CR or PR. The tumor assessment was based on 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.
Measured: 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
Time to response per independent review committee was defined as the time from date of first dose to the date of the first documented CR or PR. The tumor assessment was based on 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.
Measured: 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
ORR per investigator assessment was defined as the percentage of participants whose BOR was CR or PR. The tumor response was based on 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.
Measured: From the date of administration of the first dose of the study drug until disease progression (Up to 3 years 6 months)
Main Study Part: ORR Per IRC Based on Prince 2010 Criteria
ORR was defined as the percentage of participants whose BOR was CR, clinical complete response (CCR) or PR per IRC. The tumor response was based on Prince 2010 criteria. CR was defined as disappearance of all evidence of disease and PR was defined as regression of measurable disease and no new sites. CCR was defined as tumor residue not visible on esophagogram, computed tomography (CT), endoscopy, positron emission tomography (PET)-CT.
Measured: From the date of administration of the first dose of the study drug until disease progression (Up to 3 years 6 months)
Lead-In Part and Main Study Part: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
TEAE was defined as an adverse event that had an onset date, or a worsening in severity on or after the first dose of study drug up to the end of the study. SAE was any untoward medical occurrence that at any dose: resulted in death; life threatening required inpatient hospitalization; resulted in persistent, significant disability; was congenital anomaly/birth defect or medically important due to other reasons than mentioned criteria. Number of participants with TEAEs and SAEs were reported.
Measured: From the first dose of study drug up to 30 days after the last dose (Up to 3 years and 7 months)
Lead-In Part: Maximum Serum Concentration (Cmax) of E7777
Participants were not available for analysis in 15 mcg/kg (Cycles 3 and 5), 6 mcg/kg (Cycle 5), 9 mcg/kg (Cycles 3 and 5), 12 mcg/kg (Cycle 3), hence no Pharmacokinetic (PK) data was collected and analyzed for these doses and cycles.
Measured: Cycles 1, 3, 5 Day 1: Pre-dose up to 300 minutes post-dose (Cycle length was 21 days)
Main Study Part: Maximum Serum Concentration (Cmax) of E7777
Measured: Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 minutes post-dose (Cycle length was 21 days)
Lead-In Part: Area Under the Curve From Time 0 to Time t (AUC[0-t]) of E7777
Participants were not available for analysis in 15 mcg/kg (Cycles 3 and 5), 6 mcg/kg (Cycle 5), 9 mcg/kg (Cycles 3 and 5), 12 mcg/kg (Cycle 3), hence no PK data was collected and analyzed for these doses and cycles. Here, min*ng/mL means minute*nanogram per milliliter.
Measured: Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours Post-dose (Cycle length was 21 days)
Main Study Part: Area Under the Curve From Time 0 to Time t (AUC[0-t]) of E7777
Measured: Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
Lead-In Part: Area Under the Curve From Time 0 to Time Infinity (AUC[0-inf]) of E7777
Participants were not available for analysis in 15 mcg/kg (Cycles 3 and 5), 6 mcg/kg (Cycle 5), 9 mcg/kg (Cycles 3 and 5), 12 mcg/kg (Cycle 3), hence no PK data was collected and analyzed for these doses and cycles.
Measured: Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
Main Study Part: Area Under the Curve From Time 0 to Time Infinity (AUC[0-inf]) of E7777
Participants were not available for analysis at Cycle 3 Day 1, hence no PK data was collected and analyzed for this timepoint.
Measured: Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
Lead-In Part: Terminal Elimination Half-life (t1/2) of E7777
Participants were not available for analysis in 15 mcg/kg (Cycles 3 and 5), 6 mcg/kg (Cycle 5), 9 mcg/kg (Cycles 3 and 5), 12 mcg/kg (Cycle 3), hence no PK data was collected and analyzed for these doses and cycles.
Measured: Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
Main Study Part: Terminal Elimination Half-life (t1/2) of E7777
Measured: Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
Lead-In Part: Time to Reach Maximum (Peak) Concentration After Drug Administration (Tmax)
Participants were not available for analysis in 15 mcg/kg (Cycles 3 and 5), 6 mcg/kg (Cycle 5), 9 mcg/kg (Cycles 3 and 5), 12 mcg/kg (Cycle 3), hence no PK data was collected and analyzed for these doses and cycles.
Measured: Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
Main Study Part: Time to Reach Maximum (Peak) Concentration After Drug Administration (Tmax)
Measured: Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
Lead-In Part: Total Body Clearance (CL) of E7777
Participants were not available for analysis in 15 mcg/kg (Cycles 3 and 5), 6 mcg/kg (Cycle 5), 9 mcg/kg (Cycles 3 and 5), 12 mcg/kg (Cycle 3), hence no PK data was collected and analyzed for these doses and cycles. Here, mL/min/kg means milliliter per minute per kilogram.
Measured: Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
Main Study Part: Total Body Clearance (CL) of E7777
Participants were not available for analysis at Cycle 3 Day 1, hence no PK data was collected and analyzed for this timepoint.
Measured: Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
Lead-In Part: Volume of Distribution at Steady State (Vdss) of E7777
Participants were not available for analysis in 15 mcg/kg (Cycles 3 and 5), 6 mcg/kg (Cycle 5), 9 mcg/kg (Cycles 3 and 5), 12 mcg/kg (Cycle 3), hence no PK data was collected and analyzed for these doses and cycles.
Measured: Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
Main Study Part: Volume of Distribution at Steady State (Vdss) of E7777
Participants were not available for analysis at Cycle 3 Day 1, hence no PK data was collected and analyzed for this timepoint.
Measured: Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies
Immunogenicity was assessed by determining the anti-E7777 and anti-IL-2 antibodies in serum using validated methods. Percentage of participants testing positive for Anti-E7777 and Anti-IL-2 antibodies were reported.
Measured: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 5 Day 1
Main Study Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-IL-2 Antibodies
Immunogenicity was assessed by determining the anti-E7777 and anti-IL-2 antibodies in serum using validated methods. Percentage of participants testing positive for Anti-E7777 and Anti-IL-2 antibodies were reported.
Measured: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1
Main Study Part: Number of Participants With Objective Skin Response
Modified severity weighted assessment tool (mSWAT) was used to measure skin disease severity based on the percentage of body surface area (BSA) with patches, plaques, or tumors. Total scores were calculated by multiplying the BSA percentage for each category of lesion (patch, plaque, or tumor) by a weighting factor and adding the three sub-scores which ranged from 0 (unaffected) to 400 (severely affected). Lower scores indicated a lower degree of skin disease severity. CR corresponded to 100% clearance of skin lesions present at baseline (mSWAT score of 0). PR corresponded to 50-99% clearance of skin disease present at baseline (at least 50% reduction in mSWAT score), without new tumors.
Measured: Up to 30 months
Main Study Part: Duration of Skin Response
The duration of skin response based on the mSWAT score was defined as time from the date when criteria for skin response (CR or PR) was first met until the date of documented PD or death due to any cause for those participants with a confirmed PR or CR. mSWAT was used to measure skin disease severity based on the percentage of BSA with patches, plaques, or tumors. Total scores were calculated by multiplying the BSA percentage for each category of lesion (patch, plaque, or tumor) by a weighting factor and adding the three sub-scores which ranged from 0 (unaffected) to 400 (severely affected). Lower scores indicated a lower degree of skin disease severity. CR corresponded to 100% clearance of skin lesions present at baseline (mSWAT score of 0). PR corresponded to 50-99% clearance of skin disease present at baseline (at least 50% reduction in mSWAT score), without new tumors.
Measured: Up to 30 months
Main Study Part: Time to Skin Response
The time to skin response based on the mSWAT score was defined as time from the date of first dose to the date when criteria for skin response (CR or PR) were first met. mSWAT was used to measure skin disease severity based on the percentage of BSA with patches, plaques, or tumors. Total scores were calculated by multiplying the BSA percentage for each category of lesion (patch, plaque, or tumor) by a weighting factor and adding the three sub-scores which ranged from 0 (unaffected) to 400 (severely affected). Lower scores indicated a lower degree of skin disease severity. CR corresponded to 100% clearance of skin lesions present at baseline (mSWAT score of 0). PR corresponded to 50-99% clearance of skin disease present at baseline (at least 50% reduction in mSWAT score), without new tumors.
Measured: Up to 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2013 (estimated)
- Study start30 May 2013
- Primary completion6 Dec 2021
- Study completion14 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Persistent or Recurrent Cutaneous T-Cell LymphomaStudies of the same condition, open and under way.
- More trials run by Eisai Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 112 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eisai Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Dr. Reddy's Laboratories Limited, Citius Pharmaceuticals, Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01871727
- Sponsor's protocol ID
- E7777-G000-302
- Status last verified
- Nov 2022
- First submitted
- 28 Mar 2013
- Last updated
- 13 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 39700456
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Study to Demonstrate Safety and Efficacy of E7777 in Persistent or Recurrent Cutaneous T-Cell Lymphoma
- ClinicalTrials.gov ID
- NCT01871727
- Acronym / sponsor ID
- E7777-G000-302
- Keywords
- Persistent or Recurrent Cutaneous T-Cell Lymphoma, E7777
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 112 participants (actual)
- Lead sponsor
- Eisai Inc.Industry (pharma, biotech, devices)
- Collaborators
- Dr. Reddy's Laboratories Limited, Citius Pharmaceuticals, Inc.
- Study start
- 30 May 2013 (actual)
- Primary completion
- 6 Dec 2021 (actual)
- Study completion
- 14 Dec 2021 (actual)
- First posted
- 7 Jun 2013 (estimated)
- Results
- Posted 13 Nov 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| E7777 | Experimental | Drug: E7777 9 mcg/kg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- 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).
- History of prior therapies for CTCL: must have had prior therapy, any number of prior therapies allowed.
Key exclusion criteria (13 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| E7777 9 mcg/kgadministered by intravenous (i.v.) infusion over 60 minutes (+/-10 minutes) on 5 consecutive days during every cycle of 21 days | Drug | E7777 |
Primary outcome
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)
Time frame: Cycle 1 (cycle length was 21 days)
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.
Lead-In Part: Maximum Tolerated Dose (MTD) of E7777
Time frame: Cycle 1 (cycle length was 21 days)
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.
Main Study Part: Objective Response Rate (ORR) by Independent Review Committee (IRC) Based on Olsen 2011 Criteria
Time frame: From the date of administration of the first dose of the study drug until disease progression (Up to 3 years 6 months)
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.
26 secondary outcomes
Lead-In Part: Duration of Response (DOR) Per Investigator Assessment
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: From the date of administration of the first dose of the study drug until disease progression (Up to 3 years 6 months)
Main Study Part: ORR Per IRC Based on Prince 2010 Criteria
Time frame: From the date of administration of the first dose of the study drug until disease progression (Up to 3 years 6 months)
Lead-In Part and Main Study Part: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: From the first dose of study drug up to 30 days after the last dose (Up to 3 years and 7 months)
Lead-In Part: Maximum Serum Concentration (Cmax) of E7777
Time frame: Cycles 1, 3, 5 Day 1: Pre-dose up to 300 minutes post-dose (Cycle length was 21 days)
Main Study Part: Maximum Serum Concentration (Cmax) of E7777
Time frame: Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 minutes post-dose (Cycle length was 21 days)
Lead-In Part: Area Under the Curve From Time 0 to Time t (AUC[0-t]) of E7777
Time frame: Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours Post-dose (Cycle length was 21 days)
Main Study Part: Area Under the Curve From Time 0 to Time t (AUC[0-t]) of E7777
Time frame: Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
Lead-In Part: Area Under the Curve From Time 0 to Time Infinity (AUC[0-inf]) of E7777
Time frame: Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
Main Study Part: Area Under the Curve From Time 0 to Time Infinity (AUC[0-inf]) of E7777
Time frame: Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
Lead-In Part: Terminal Elimination Half-life (t1/2) of E7777
Time frame: Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
Main Study Part: Terminal Elimination Half-life (t1/2) of E7777
Time frame: Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
Lead-In Part: Time to Reach Maximum (Peak) Concentration After Drug Administration (Tmax)
Time frame: Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
Main Study Part: Time to Reach Maximum (Peak) Concentration After Drug Administration (Tmax)
Time frame: Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
Lead-In Part: Total Body Clearance (CL) of E7777
Time frame: Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
Main Study Part: Total Body Clearance (CL) of E7777
Time frame: Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
Lead-In Part: Volume of Distribution at Steady State (Vdss) of E7777
Time frame: Cycles 1, 3, 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
Main Study Part: Volume of Distribution at Steady State (Vdss) of E7777
Time frame: Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 hours post-dose (Cycle length was 21 days)
Lead-In Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-interleukin (IL)-2 Antibodies
Time frame: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 5 Day 1
Main Study Part: Percentage of Participants Testing Positive for Anti-E7777 and Anti-IL-2 Antibodies
Time frame: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1
Main Study Part: Number of Participants With Objective Skin Response
Time frame: Up to 30 months
Main Study Part: Duration of Skin Response
Time frame: Up to 30 months
Main Study Part: Time to Skin Response
Time frame: Up to 30 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39700456Foss 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
22 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing E7777 9 mcg/kg in people with Persistent or Recurrent Cutaneous T-Cell Lymphoma, run by Eisai Inc. at 22 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in United States, Australia, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Nov 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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) (time frame: Cycle 1 (cycle length was 21 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01871727, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2024.