Clinical Trials /

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

NCT01871727

Description:

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.

Related Conditions:
  • Primary Cutaneous T Cell Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: E7777-G000-302
  • NCT ID: NCT01871727

Conditions

  • Persistent or Recurrent Cutaneous T-Cell Lymphoma

Interventions

DrugSynonymsArms
E7777 9 mcg/kgE7777

Purpose

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.

Detailed Description

      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
      Follow-up Period.
    

Trial Arms

NameTypeDescriptionInterventions
E7777Experimental
  • E7777 9 mcg/kg

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 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
             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/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
                  normal (ULN).

               -  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

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose-limiting toxicities (DLTs) in the Lead-In Part
Time Frame:Cycle 1 (21 days)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Duration of Response (DOR)
Time Frame:Day 1 until disease progression/recurrence, or up to 12 months (Lead-in Part) and Day 1 until disease progression/recurrence, or up to 30 months (Main Study)
Safety Issue:
Description:
Measure:Time to Response (TTR)
Time Frame:Up to 12 months (Lead-In Part) and up to 30 months (Main study)
Safety Issue:
Description:
Measure:Objective Response Rate (ORR)
Time Frame:Day 1 until disease progression/recurrence, up to 12 months (Lead-in Part) and Day 1 until disease progression/recurrence, up to 30 months (by using Prince (2010) criteria in Main Study)
Safety Issue:
Description:
Measure:Number of Participants with Any Adverse Event and Any Serious Adverse Event (SAE)
Time Frame:From first dose of the study drug until 30 days after the last dose, or up to 30 months
Safety Issue:
Description:
Measure:Maximum Drug Concentration (Cmax)
Time Frame:Day 1 of Cycles 1, 3, 5,and 8 (Lead-In Part) and Day 1 of Cycles 1, 3, 5, and 8 for the first 12 participants and Day 1 of Cycle 1 for all other participants (Main Study)
Safety Issue:
Description:Blood samples will be collected at pre-dose; 30 minutes (min) after the start of the infusion; at the end of the infusion; and 30, 60, 90, 120, 180, 240, and 300 min postinfusion stop. Sparse samples will be collected at pre-dose, at the end of the infusion, and between 60 and 180 min postinfusion.
Measure:Area Under the Curve from Time 0 to Time t (AUC[0-t])
Time Frame:Day 1 of Cycles 1, 3, 5,and 8 (Lead-In Part) and Day 1 of Cycles 1, 3, 5, and 8 for the first 12 participants and Day 1 of Cycle 1 for all other participants (Main Study)
Safety Issue:
Description:Blood samples will be collected at pre-dose; 30 minutes (min) after the start of the infusion; at the end of the infusion; and 30, 60, 90, 120, 180, 240, and 300 min postinfusion stop. Sparse samples will be collected at pre-dose, at the end of the infusion, and between 60 and 180 min postinfusion.
Measure:Area Under the Curve from Time 0 to Time Infinity (AUC[0-inf])
Time Frame:Day 1 of Cycles 1, 3, 5,and 8 (Lead-In Part) and Day 1 of Cycles 1, 3, 5, and 8 for the first 12 participants and Day 1 of Cycle 1 for all other participants (Main Study)
Safety Issue:
Description:Blood samples will be collected at pre-dose; 30 minutes (min) after the start of the infusion; at the end of the infusion; and 30, 60, 90, 120, 180, 240, and 300 min postinfusion stop. Sparse samples will be collected at pre-dose, at the end of the infusion, and between 60 and 180 min postinfusion.
Measure:Terminal Elimination Half-life (t1/2)
Time Frame:Day 1 of Cycles 1, 3, 5,and 8 (Lead-In Part) and Day 1 of Cycles 1, 3, 5, and 8 for the first 12 participants and Day 1 of Cycle 1 for all other participants (Main Study)
Safety Issue:
Description:Blood samples will be collected at pre-dose; 30 minutes (min) after the start of the infusion; at the end of the infusion; and 30, 60, 90, 120, 180, 240, and 300 min postinfusion stop. Sparse samples will be collected at pre-dose, at the end of the infusion, and between 60 and 180 min postinfusion.
Measure:Percentage of Participants Testing Positive for Anti-E7777 and Anti-IL-2 Antibodies
Time Frame:Baseline; 10. Day 1 of Cycles 1, 2, 3, 5, and 8 (for Anti-E7777 and Anti-IL-2); Anti-IL-2 is to be tested at 6 month and thereafter every year until antibody levels decrease to baseline levels
Safety Issue:
Description:
Measure:Number of Participants with Skin Response in the Main Study
Time Frame:Day 1 until disease progression/recurrence, or up to 30 months
Safety Issue:
Description:
Measure:Duration of Skin Response in the Main Study
Time Frame:Day 1 until disease progression/recurrence, or up to 30 months
Safety Issue:
Description:
Measure:Time to Skin Response in the Main Study
Time Frame:Up to 30 months
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Eisai Inc.

Trial Keywords

  • Persistent or Recurrent Cutaneous T-Cell Lymphoma
  • E7777

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