Clinical Trials /

Lisocabtagene Maraleucel (JCAR017) as Second-Line Therapy (TRANSCEND-PILOT-017006)

NCT03483103

Description:

This is a Phase 2, open-label, multicenter study to determine the efficacy and safety of lisocabtagene maraleucel (JCAR017) in adult subjects who have relapsed from, or are refractory to, a single line of immunochemotherapy for aggressive B-cell non-Hodgkin lymphoma (NHL) and are ineligible for hematopoietic stem cell transplant (based on age, performance status, and/or comorbidities). Subjects will receive treatment with lisocabtagene maraleucel and will be followed for 2 years for safety, pharmacokinetics and biomarkers, disease status, quality of life, and survival.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • Double-Hit Lymphoma
  • Follicular Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Lisocabtagene Maraleucel (JCAR017) as Second-Line Therapy (TRANSCEND-PILOT-017006)
  • Official Title: A Phase 2 Study of Lisocabtagene Maraleucel (JCAR017) as Second-Line Therapy in Adult Patients With Aggressive B-cell NHL (017006)

Clinical Trial IDs

  • ORG STUDY ID: 017006
  • NCT ID: NCT03483103

Conditions

  • Lymphoma, Non-Hodgkin
  • Lymphoma, Nonhodgkin
  • Lymphoma, B-Cell
  • Lymphoma, Large B-Cell, Diffuse

Interventions

DrugSynonymsArms
lisocabtagene maraleucelJCAR017, liso-celTreatment

Purpose

This is a Phase 2, open-label, multicenter study to determine the efficacy and safety of lisocabtagene maraleucel (JCAR017) in adult subjects who have relapsed from, or are refractory to, a single line of immunochemotherapy for aggressive B-cell non-Hodgkin lymphoma (NHL) and are ineligible for hematopoietic stem cell transplant (based on age, performance status, and/or comorbidities). Subjects will receive treatment with lisocabtagene maraleucel and will be followed for 2 years for safety, pharmacokinetics and biomarkers, disease status, quality of life, and survival.

Trial Arms

NameTypeDescriptionInterventions
TreatmentExperimentalLisocabtagene maraleucel at a dose of 100×10^6 CAR+ T cells (50×10^6 CD8+ CAR+ T cells and 50×10^6 CD4+ CAR+ T cells), will be given IV in a single-dose schedule on Day 1 (between 2 and 7 days following the completion of lymphodepleting chemotherapy).
  • lisocabtagene maraleucel

Eligibility Criteria

        Inclusion Criteria:

          -  Confirmation of relapsed or refractory aggressive B-cell non-Hodgkin lymphoma of the
             following histology at relapse: diffuse large B-cell lymphoma (DLBCL), not otherwise
             specified (NOS; de novo or transformed follicular lymphoma [tFL]), high-grade B-cell
             lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology
             (double/triple hit lymphoma [DHL/THL]), and follicular lymphoma Grade 3B per WHO 2016
             classification

          -  Previous treatment must include treatment with a single line of chemoimmunotherapy
             containing an anthracycline and a CD20-targeted agent

          -  Subjects must be deemed ineligible for both high-dose chemotherapy and hematopoietic
             stem cell transplant (based on age, performance status and/or comorbidities) while
             also having adequate organ function for CAR T cell treatment.

          -  Positron emission tomography (PET)-positive disease

          -  Histological confirmation of diagnosis at last relapse. Enough tumor material must be
             available for central confirmation of diagnosis, otherwise a new tumor biopsy is
             mandated.

          -  ECOG performance status of 0, or 1, or 2

          -  Adequate vascular access for leukapheresis procedure (either peripheral line or
             surgically-placed line)

        Exclusion Criteria:

          -  Subjects with central nervous system (CNS)-only involvement by malignancy (note:
             subjects with secondary CNS involvement are allowed on study)

          -  History of another primary malignancy that has not been in remission for at least 2
             years.

          -  Previous treatment with CD19-targeted therapy, with the exception of prior
             lisocabtagene maraleucel treatment in this protocol for subjects receiving retreatment

          -  Active hepatitis B or hepatitis C infection at the time of screening

          -  History of or active human immunodeficiency virus (HIV) infection at the time of
             screening

          -  Uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate
             antibiotics or other treatment at the time of leukapheresis or lisocabtagene
             maraleucel administration

          -  History of any one of the following cardiovascular conditions within the past 6
             months: Class III or IV heart failure as defined by the New York Heart Association,
             cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other
             clinically significant cardiac disease

          -  History or presence of clinically relevant CNS pathology

          -  Nursing women

          -  Subject does not meet protocol-specified washout periods for prior treatments

          -  Prior hematopoietic stem cell transplant

          -  Tumor invasion of venous or arterial vessels

          -  Deep venous thrombosis (DVT) or pulmonary embolism (PE) within 3 months of
             leukapheresis and/or DVT or PE that requires ongoing therapeutic levels of
             anticoagulation
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Antitumor activity
Time Frame:Through Month 24
Safety Issue:
Description:Overall response rate (complete response + partial response) based on "Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification"

Secondary Outcome Measures

Measure:Adverse events
Time Frame:90 days
Safety Issue:
Description:Proportion of subjects experiencing adverse events
Measure:Laboratory abnormalities
Time Frame:90 days
Safety Issue:
Description:Proportion of subjects experiencing laboratory abnormalities
Measure:Antitumor activity
Time Frame:Through Month 24
Safety Issue:
Description:Complete response rate based on "Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification"
Measure:Antitumor activity
Time Frame:Through Month 24
Safety Issue:
Description:Duration of response
Measure:Maximum concentration (Cmax) of lisocabtagene maraleucel in blood
Time Frame:Through Month 24
Safety Issue:
Description:Maximum concentration of lisocabtagene maraleucel in blood
Measure:Time of the maximum concentration (Tmax) of lisocabtagene maraleucel in blood
Time Frame:Through Month 24
Safety Issue:
Description:Time of the maximum concentration of lisocabtagene maraleucel in blood
Measure:Area under the curve of (AUC) lisocabtagene maraleucel concentration in blood
Time Frame:Through Month 24
Safety Issue:
Description:Area under the curve of lisocabtagene maraleucel in blood
Measure:Progression-free survival
Time Frame:Through Month 24
Safety Issue:
Description:Progression-free survival
Measure:Event-free survival
Time Frame:Through Month 24
Safety Issue:
Description:Event-free survival
Measure:Overall survival
Time Frame:Through Month 24
Safety Issue:
Description:Overall survival
Measure:Health-related quality of life and health economics and outcomes research
Time Frame:Through Month 24
Safety Issue:
Description:The European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 is a validated quality of life measure applicable to subjects with any cancer diagnosis. It is composed of 30 items that address general physical symptoms, physical functioning, fatigue and malaise, and social and emotional functioning. Subscale scores are transformed to a 0 to 100 scale, with higher scores on functional scales indicating better function and higher scores on symptom scales indicating worse symptoms. A 10 point change in the scoring is considered to be a meaningful change in HRQoL.
Measure:Health-related quality of life and health economics and outcomes research
Time Frame:Through Month 24
Safety Issue:
Description:The EuroQol-5D (EQ-5D) is a standardized measure of health status developed by the EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal. The EQ-5D-5L consists of the EQ-5D-5L descriptive system and the EQ Visual Analogue scale (EQ VAS). The descriptive system comprises dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). Each dimension has 5 levels (no problems, slight problems, moderate problems, severe problems, extreme problems). The VAS rating scale is a vertical 20 cm visual analogue scale with the end points labeled best imaginable health state at the top and worst imaginable health state at the bottom having numeric values of 100 and 0 respectively. The participant is asked to indicate his/her health state by ticking (or placing a cross) in the box against the most appropriate statement in each of the 5 dimensions.
Measure:Health-related quality of life and health economics and outcomes research
Time Frame:Through month 24
Safety Issue:
Description:The Functional Assessment of Cancer Treatment-Lymphoma (FACT-Lym) consists of the FACT-General scale and a 15-item lymphoma-specific additional concerns subscale (LYM). This scale addresses symptoms and functional limitations that are important to lymphoma patients. Only the LYM subscale will be administered in this study. The LYM items are scored on a 0 ("Not at all") to 4 ("Very much") response scale. Items are aggregated to a single score on a 0-60 scale.
Measure:Health-related quality of life and health economics and outcomes research
Time Frame:Through Month 24
Safety Issue:
Description:Numbers of intensive care unit inpatient days and non-ICU inpatient days and reasons for hospitalization

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Juno Therapeutics, Inc.

Trial Keywords

  • JCAR017
  • lisocabtagene maraleucel
  • NHL
  • chimeric antigen receptor
  • CAR
  • CAR T cell
  • autologous T cell therapy
  • immunotherapy
  • cell therapy
  • liso-cel

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