A Clinical Study to Demonstrate Safety and Efficacy of E7777 in Persistent or Recurrent Cutaneous T-Cell Lymphoma
Overview
- Phase
- Phase 3
- Intervention
- E7777 9 mcg/kg
- Conditions
- Persistent or Recurrent Cutaneous T-Cell Lymphoma
- Sponsor
- Eisai Inc.
- Enrollment
- 112
- Locations
- 22
- Primary Endpoint
- 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)
- Status
- Completed
- Last Updated
- last year
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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 E
Exclusion Criteria
- Not provided
Arms & Interventions
E7777
Intervention: E7777 9 mcg/kg
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- 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))
- Main Study Part: ORR Per IRC Based on Prince 2010 Criteria(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)(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(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(Cycles 1, 3 and 5 Day 1: Pre-dose up to 300 minutes 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(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 t (AUC[0-t]) of E7777(Cycles 1, 3, 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(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(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(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(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)(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)(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(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(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(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(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(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(Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1)
- Main Study Part: Number of Participants With Objective Skin Response(Up to 30 months)
- Main Study Part: Duration of Skin Response(Up to 30 months)
- Main Study Part: Time to Skin Response(Up to 30 months)