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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 (TRANSCEND-OUTREACH-007)

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ClinicalTrials.gov Identifier: NCT03744676
Recruitment Status : Recruiting
First Posted : November 16, 2018
Last Update Posted : February 18, 2021
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Juno Therapeutics, a Subsidiary of Celgene

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
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 Biological: lisocabtagene maraleucel Phase 2

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 29, 2018
Estimated Primary Completion Date : October 30, 2023
Estimated Study Completion Date : October 30, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arms and Interventions
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Arm Intervention/treatment
Experimental: Lisocabtagene maraleucel
Subjects 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.
 Biological: lisocabtagene maraleucel
lisocabtagene maraleucel will be administered as single dose intravenous (IV) injection
Other Names:
  • JCAR017
  • liso-cel


Outcome Measures
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Primary Outcome Measures :
  1. Adverse events [ Time Frame: Through Month 24 ]
    Proportion of subjects experiencing cytokine release syndrome, neurotoxicity, prolonged cytopenias, infections AE of Grade 3 or higher


Secondary Outcome Measures :
  1. Adverse events [ Time Frame: Through Month 24 ]
    Proportion of subjects experiencing all AEs and laboratory abnormalities

  2. Adverse events [ Time Frame: Through Month 24 ]
    Median time to onset and to resolution of cytokine release syndrome and neurotoxicity of Grade 3 or higher

  3. Adverse Events [ Time Frame: Through Month 24 ]
    Management of cytokine release syndrome and neurotoxicity

  4. Adverse Events [ Time Frame: Through Month 24 ]
    Of subjects monitored in the outpatient setting, the proportion of subjects experiencing all AEs and laboratory abnormalities

  5. Objective response rate (ORR) [ Time Frame: Through Month 24 ]
    Objective response rate (ORR [complete response + partial response]) according to the Lugano Classification

  6. Complete response (CR) rate [ Time Frame: Through Month 24 ]
    Complete response rate according to the Lugano Classification

  7. Duration of response (DOR) and duration of complete response (DoCR) [ Time Frame: Through Month 24 ]
    Each defined as time from first response to progressive disease (PD) or death

  8. Progression-free Survival (PFS) [ Time Frame: Through Month 24 ]
    Time from infusion of lisocabtagene maraleucel to PD or death, whichever is earlier

  9. Overall Survival (OS) [ Time Frame: Through Month 24 ]
    Defined as the time from infusion of lisocabtagene maraleucel to the date of death

  10. Pharmacokinetics- Maximum concentration (Cmax) [ Time Frame: Through Month 24 ]
    Maximum concentration of lisocabtagene maraleucel

  11. Pharmacokinetics- Time of the maximum concentration (Tmax) [ Time Frame: Through Month 24 ]
    Time to peak concentration of lisocabtagene maraleucel in the blood

  12. Pharmacokinetics- area under the curve [ Time Frame: Through Month 24 ]
    Area under the curve of lisocabtagene maraleucel in blood

  13. Health-related quality of life questionnaires [ Time Frame: Through Month 24 ]
    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.

  14. Health-related quality of life questionnaires [ Time Frame: Through Month 24 ]
    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.

  15. Health economics and outcomes research [ Time Frame: Through Month 24 ]
    For subjects hospitalized post-treatement, the number of days the subjects were hospitalized, including the number of days that the subjects were in the Intensive Care Unit (ICU) and non-ICU ward

  16. Health economics and outcomes research [ Time Frame: Through Month 24 ]
    The percentage of lisocabtagene maraleucel-treated subjects hospitalized post-treatment for each reason will be reported.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 indolent histologies, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology, primary mediastinal B-cell lymphoma(PMBCL), and follicular lymphoma Grade 3B. 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, cerebral edema, 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
  • Progressive vascular tumor invasion, thrombosis, or embolism
  • Venous thrombosis or embolism not managed on stable regimen of anticoagulation
  • Uncontrolled medical, psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol; or unwillingness or inability to follow the procedures required in the protocol
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03744676


Contacts
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Contact: Associate Director Clinical Trial Disclosure 1-888-260-1599 clinicaltrialdisclosure@celgene.com

Locations
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Sponsors and Collaborators
Juno Therapeutics, a Subsidiary of Celgene
Bristol-Myers Squibb
Investigators
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Study Director: Nick Trede, MD, PhD Juno Therapeutics, Inc.
More Information
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Responsible Party: Juno Therapeutics, a Subsidiary of Celgene
ClinicalTrials.gov Identifier: NCT03744676    
Other Study ID Numbers: 017007
First Posted: November 16, 2018    Key Record Dates
Last Update Posted: February 18, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Information relating to our policy on data sharing and the process for requesting data can be found at the following link:

https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: See Plan Description
Access Criteria: See Plan Description
URL: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Juno Therapeutics, a Subsidiary of Celgene:
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
Additional relevant MeSH terms:
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Lymphoma
Neoplasms
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
 Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Disease
Pathologic Processes