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A Safety Trial of Lisocabtagene Maraleucel (JCAR017) for Relapsed and Refractory (R/R) B-cell Non-Hodgkin Lymphoma (NHL) in the Outpatient Setting

NCT03744676

Description:

This is an open-label, multicenter, Phase 2 study to determine the safety, PK, and efficacy of lisocabtagene maraleucel (JCAR017) in subjects who have relapsed from, or are refractory to, two lines of immunochemotherapy for aggressive B-cell non-Hodgkin lymphoma (NHL) in the outpatient setting. Subjects will receive treatment with JCAR017 and will be followed for up to 2 years.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Safety Trial of Lisocabtagene Maraleucel (JCAR017) for Relapsed and Refractory (R/R) B-cell Non-Hodgkin Lymphoma (NHL) in the Outpatient Setting
  • Official Title: A Safety Trial of Lisocabtagene Maraleucel (JCAR017) for Relapsed and Refractory (R/R) B-cell Non-Hodgkin Lymphoma (NHL) in the Outpatient Setting

Clinical Trial IDs

  • ORG STUDY ID: 017007
  • NCT ID: NCT03744676

Conditions

  • Lymphoma, Non-Hodgkin
  • Lymphoma
  • Lymphoma, B-Cell
  • Lymphoma, Large B-Cell, Diffuse
  • Neoplasms
  • Neoplasms by Histologic Type
  • Lymphoproliferative Disorders
  • Lymphatic Diseases
  • Immunoproliferative Disorders
  • Immune System Disorder

Interventions

DrugSynonymsArms
lisocabtagene maraleucelJCAR017Lisocabtagene maraleucel

Purpose

This is an open-label, multicenter, Phase 2 study to determine the safety, PK, and efficacy of lisocabtagene maraleucel (JCAR017) in subjects who have relapsed from, or are refractory to, two lines of immunochemotherapy for aggressive B-cell non-Hodgkin lymphoma (NHL) in the outpatient setting. Subjects will receive treatment with JCAR017 and will be followed for up to 2 years.

Detailed Description

      This is an open-label, multicenter, Phase 2 study to assess the safety and antitumor activity
      in adult patients with relapsed or refractory B-cell non-Hodgkin Lymphoma when administered
      with lisocabtagene maraleucel (JCAR017) in the outpatient setting.

      Upon the successful product generation of lisocabtagene maraleucel, subjects will enter the
      treatment phase of the study. Treatment will include lymphodepleting chemotherapy followed by
      lisocabtagene maraleucel administration. Subjects will then enter the post-treatment
      follow-up phase of the study and will be followed for approximately 24 months for safety,
      disease status, health-related quality of life (HRQoL), and survival. Long-term follow-up
      will continue under a separate long-term follow-up protocol, per health regulatory authority
      guidelines, currently up to 15 years after the last lisocabtagene maraleucel administration.
    

Trial Arms

NameTypeDescriptionInterventions
Lisocabtagene maraleucelExperimentalSubjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of lisocabtagene maraleucel. During lisocabtagene maraleucel production, subjects may receive low-dose chemotherapy for disease control. Upon successful generation of lisocabtagene maraleucel product, subjects will receive treatment which will include lymphodepleting chemotherapy followed by one dose of lisocabtagene maraleucel administered by intravenous (IV) injection.
  • lisocabtagene maraleucel

Eligibility Criteria

        Inclusion Criteria:

          -  Age ≥ 18 years at the time of consent

          -  Relapsed or refractory B-cell NHL of the following histologies: diffuse large B cell
             lymphoma (DLBCL) not otherwise specified; includes biopsy-confirmed transformed DLBCL
             from follicular lymphoma, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6
             rearrangements with DLBCL histology. Subjects must have been treated with an
             anthracycline and rituximab (or other CD20-targeted agent) and have relapsed or
             refractory disease after at least 2 systemic lines of therapy for DLBCL or after
             auto-HSCT.

          -  Positron-emission tomography-positive disease by Lugano Classification

          -  Eastern Cooperative Oncology Group performance status of 0 to 1

          -  Adequate bone marrow, renal, hepatic, pulmonary, cardiac organ function

          -  Adequate vascular access for leukapheresis procedure

          -  Subjects who have received previous CD19-targeted therapy must have CD19-positive
             lymphoma confirmed on a biopsy since completing the prior CD19-targeted therapy

          -  Subjects must agree to use appropriate contraception.

        Exclusion Criteria:

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

          -  History of prior allogeneic hematopoietic stem cell transplant

          -  Treatment with alemtuzumab within 6 months of leukapheresis, or treatment with
             fludarabine or cladribine within 3 months of leukapheresis

          -  History of another primary malignancy that has not been in remission for at least 2
             years.The following are examples of exceptions from the 2-year limit: nonmelanoma skin
             cancer, definitively-treated stage 1 solid tumor with a low risk of recurrence,
             curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsy
             or a squamous intraepithelial lesion on a Papanicolau smear.

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

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

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

          -  Presence of acute or chronic graft-versus-host disease

          -  History of clinically significant cardiac conditions within the past 6 months

          -  History or presence of clinically relevant CNS pathology such as epilepsy/seizure,
             paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease,
             cerebellar disease, organic brain syndrome, or psychosis

          -  Pregnant or nursing women.

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

          -  Prior CAR T-cell or other genetically modified T-cell therapy
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse events
Time Frame:Through Month 24
Safety Issue:
Description:Proportion of subjects experiencing cytokine release syndrome, neurotoxicity, prolonged cytopenias, infections AE of Grade 3 or higher

Secondary Outcome Measures

Measure:Adverse events
Time Frame:Through Month 24
Safety Issue:
Description:Proportion of subjects experiencing all AEs and laboratory abnormalities
Measure:Adverse events
Time Frame:Through Month 24
Safety Issue:
Description:Median time to onset and to resolution of cytokine release syndrome and neurotoxicity of Grade 3 or higher
Measure:Adverse Events
Time Frame:Through Month 24
Safety Issue:
Description:Management of cytokine release syndrome and neurotoxicity
Measure:Objective response rate (ORR)
Time Frame:Through Month 24
Safety Issue:
Description:Objective response rate (ORR [complete response + partial response]) according to the Lugano Classification
Measure:Complete response (CR) rate
Time Frame:Through Month 24
Safety Issue:
Description:Complete response rate according to the Lugano Classification
Measure:Duration of response (DOR) and duration of complete response (DoCR)
Time Frame:Through Month 24
Safety Issue:
Description:Each defined as time from first response to progressive disease (PD) or death
Measure:Progression-free Survival (PFS)
Time Frame:Through Month 24
Safety Issue:
Description:Time from infusion of lisocabtagene maraleucel to PD or death, whichever is earlier
Measure:Overall Survival (OS)
Time Frame:Through Month 24
Safety Issue:
Description:Defined as the time from infusion of lisocabtagene maraleucel to the date of death
Measure:Pharmacokinetics- Maximum concentration (Cmax)
Time Frame:Through Month 24
Safety Issue:
Description:Maximum concentration of lisocabtagene maraleucel
Measure:Pharmacokinetics- Time of the maximum concentration (Tmax)
Time Frame:Through Month 24
Safety Issue:
Description:Time to peak concentration of lisocabtagene maraleucel in the blood
Measure:Pharmacokinetics- area under the curve
Time Frame:Through Month 24
Safety Issue:
Description:Area under the curve of lisocabtagene maraleucel in blood
Measure:Health-related quality of life questionnaires
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.
Measure:Health-related quality of life questionnaires
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 economics and outcomes research
Time Frame:Through Month 24
Safety Issue:
Description:The number of days the patient was hospitalized post-treatment, including the number of days that the patient was in the Intensive Care Unit (ICU) and non-ICU
Measure:Health economics and outcomes research
Time Frame:Through Month 24
Safety Issue:
Description:The percentage of lisocabtagene maraleucel-treated subjects hospitalized post-treatment for each reason will be reported.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Juno Therapeutics, Inc.

Trial Keywords

  • Lisocabtagene maraleucel
  • liso-cel
  • JCAR017
  • relapse
  • refractory
  • B-Cell Non-Hodgkin Lymphoma
  • NHL
  • chimeric antigen receptor
  • CAR
  • CAR T cell
  • autologous T cell therapy
  • immunotherapy
  • cell therapy
  • B-cell malignancies

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