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Lymphoma, Non-HodgkinPhase 2NCT03744676

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)

A Phase 2 study testing lisocabtagene maraleucel in people with Lymphoma, Non-Hodgkin and Lymphoma, run by Juno Therapeutics, a Subsidiary of Celgene at 23 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphoma, Non-Hodgkin, Lymphoma, Lymphoma, B-Cell
What is being tested?
lisocabtagene maraleucel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
104 participants
Where
23 sitesUnited States
Study dates
29 Nov 2018to 22 Sep 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 16Show fewer
  • 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

Trial locations and contacts

23 sites in 1 country.

23 sites in 1 country

United States23 sites

  • Local Institution - 0041

    Albany, New York, 12208

  • Local Institution - 0039

    Cincinnati, Ohio, 45236

  • Local Institution - 0097

    Dallas, Texas, 75230

  • Local Institution - 0060

    Denver, Colorado, 80218

  • Local Institution - 0052

    East Brunswick, New Jersey, 08816

  • Local Institution - 0098

    Eugene, Oregon, 97401

  • Local Institution - 0037

    Greenville, South Carolina, 29615

  • Local Institution - 0065

    Indianapolis, Indiana, 46237

  • Lancaster General Hospital

    Lancaster, Pennsylvania, 17604

  • Local Institution - 0057

    Los Angeles, California, 90048

  • Local Institution - 0064

    Louisville, Kentucky, 40207

  • Local Institution - 0089

    Miami, Florida, 33176

  • Local Institution - 0066

    Morristown, New Jersey, 07962

  • Local Institution - 0063

    Nashville, Tennessee, 37203

  • Local Institution - 0036

    Norfolk, Virginia, 23502

  • Local Institution - 0081

    Orlando, Florida, 32804

  • Local Institution - 0051

    Portland, Oregon, 97213

  • Local Institution - 0074

    Salt Lake City, Utah, 84143

  • Local Institution - 0061

    San Antonio, Texas, 78229

  • Local Institution - 0101

    Southfield, Michigan, 48075

  • Baylor Scott and White Health

    Temple, Texas, 76508

  • Local Institution - 0096

    Tyler, Texas, 75702

  • Local Institution - 0069

    Wichita, Kansas, 67124

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
lisocabtagene maraleucel
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
Medical subject headings
Lymphoma, Non-Hodgkin, Lymphoma, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Neoplasms, Neoplasms by Histologic Type, Lymphoproliferative Disorders, Lymphatic Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • lisocabtagene maraleucelBiological

    Also called JCAR017, liso-cel

    lisocabtagene maraleucel will be administered as single dose intravenous (IV) injection

Study groups in NCT03744676
Study groupRoleWhat they receive
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.
Receives: Biological: lisocabtagene maraleucel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Cytokine Release Syndrome (CRS) Adverse Events Grade ≥ 3

    Cytokine release syndrome is characterized by high fever, fatigue, nausea, headache, dyspnea, tachycardia, rigors, hypotension, hypoxia, myalgia/arthralgia, and anorexia.

    Incidence of Grade ≥ 3 CRS, based on the TEAE with MedDRA PT "Cytokine release syndrome," graded according to the grading scale adapted from Lee (Lee 2014).

    Measured: From first dose to 90 days following first dose (up to approximately 90 days)

  2. Percentage of Participants With Neurotoxicity (NT) Adverse Events Grade ≥ 3

    NT events have also been reported and may include neurologic symptoms such as altered mental status, aphasia, altered level of consciousness, and seizures or seizure-like activity.

    Incidence of Grade ≥ 3 NT, defined as an Investigator-identified TEAE considered neurotoxicity related to JCAR017.

    Measured: From first dose to 90 days following first dose (up to approximately 90 days)

  3. Percentage of Participants With Infection Adverse Events Grade ≥ 3

    Incidence of treatment-emergent Grade ≥ 3 infections, defined using MedDRA SOC.

    Measured: From first dose to 90 days following first dose (up to approximately 90 days)

  4. Percentage of Participants With Grade ≥ 3 Prolonged Cytopenia at Day 29.

    Prolonged cytopenia is defined as the occurrence of Grade ≥ 3 cytopenia not resolved by the Day 29 visit, based on laboratory results of low hemoglobin, absolute neutrophil count decreased, and platelet count decreased. The frequency of subjects experiencing each individual laboratory abnormality and the total number with at least 1 abnormality will be summarized, as will recovery from prolonged cytopenia after Day 29.

    Measured: At Day 29 after first treatment

Secondary outcomes (22)

  1. Number of Participants With Adverse Events

    Measured: From first dose to 90 days following first dose (up to approximately 90 days)

  2. Number of Participants With Clinically Significant Laboratory Abnormalities- Hematology

    Measured: From first dose to up to 41 months

  3. Number of Participants With Clinically Significant Laboratory Abnormalities- Chemistry

    Measured: From first dose to up to 41 months

  4. Number of Participants With Adverse Events Grade ≥ 3

    Measured: From first dose to 90 days following first dose (up to approximately 90 days)

  5. Time to Onset and Time to Resolution of Grade ≥ 3 Cytokine Release Syndrome (CRS)

    Measured: From first dose to up to approximately 41 months

  6. Time to Onset and Time to Resolution of Grade ≥ 3 Neurotoxicity (NT)

    Measured: From first dose to up to approximately 41 months

  7. Number of Participants Administered Tocilizumab and Corticosteroid for Management of Cytokine Release Syndrome (CRS)

    Measured: From first dose to up to approximately 41 months

  8. Number of Participants Administered Tocilizumab and Corticosteroid for Management of Neurotoxicity (NT)

    Measured: From first dose to up to study completion (Approximately 57 Months and 24 days)

  9. Objective Response Rate (ORR)

    The Percentage of participants with a best overall response (BOR) of either CR or PR based on the Lugano 2014 criteria.

    Disease response will be determined according to the "Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification"

    Complete response is defined as:

    1. Score 1, 2, or 3a with or without residual mass
    2. No evidence of FDG-avid disease in marrow

    Partial Response is defined as:

    1. Score 4 or 5a with reduced uptake compared with baseline and residual masses of any size
    2. Bone marrow with residual uptake higher than in normal marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed). If there are persistent focal changes in marrow in the context of a nodal response, should consider further evaluation with MRI, biopsy, or interval scan.

    Measured: From first dose to up to approximately 41 months

  10. Complete Response Rate (CRR)

    The Percentage of participants with a best overall response (BOR) with CR based on the Lugano 2014 criteria.

    Disease response will be determined according to the "Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification"

    Complete response is defined as:

    1. Score 1, 2, or 3a with or without residual mass
    2. No evidence of FDG-avid disease in marrow

    Measured: From first dose to up to approximately 41 months

  11. Duration of Response (DoR) and Duration of Complete Response (DoCR)

    Duration of response (DOR) is defined as the time from the first documentation of response (CR or PR) after JCAR017 infusion to disease progression or death from any cause, whichever occurs first.

    Duration of response (DOR) if BOR is CR is defined for subjects with a BOR of CR as the time from the first documentation of response (CR or PR) after JCAR017 infusion to earlier of disease progression or death from any cause.

    Measured: From first dose to up to approximately 41 months

  12. Progression Free Survival (PFS)

    Progression-free survival is defined as the time from infusion of JCAR017 to progressive disease or death, whichever is earlier. If a subject does not have an event for the PFS analysis, the subject will be censored.

    Progressive Disease is defined as:

    1. Score 4 or 5a with an increase in intensity of uptake from nadir
    2. New FDG-avid foci consistent with lymphoma (may need biopsy or repeat scan if uncertain about etiology of foci).
    3. Investigator assessed clinical progression

    Measured: From first dose to up to study completion (Approximately 57 Months and 24 days)

  13. Overall Survival (OS)

    Overall survival is defined as the time from infusion of JCAR017 to the date of death. For assessment of OS, data from surviving participants will be censored at the last time that the participant is known to be alive. The OS analysis will include all available survival information from the long-term follow-up study if applicable.

    Measured: From first dose to up to study completion (Approximately 57 Months and 24 days)

  14. Area Under the Blood Concentration-time Curve From Time to Zero to 28 Days After Dosing AUC (0-28)

    Measured: 28days after first dose

  15. Maximum Observed Blood Concentration (Cmax)

    Measured: 28days after first dose

  16. Time of Maximum Observed Blood Concentration (Tmax)

    Measured: 28days after first dose

  17. Mean Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30

    The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100. A higher scale score represents a higher level of well-being and better ability of daily functioning. Thus, a high score for a functional scale represents a high/healthy level of functioning; a high score for the global health status/HRQoL represents a high HRQoL, but a high score for a symptom scale/item represents a high level of symptomatic problem.

    Measured: From Enrollment to end of follow up, approximately 26 months

  18. Mean Change From Baseline in EuroQol Instrument EQ-5D-5L.

    The European Quality of Life 5D-5L Scale (EQ-5D-5L) assesses general health-related quality of life. Health is defined in 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Responses are coded so that a '1' indicates no problem, and '5' indicates the most serious problem. The responses for the 5 dimensions are combined in a 5-digit number. The EQ-5D-5L health utility index (HUI) is assessed using the Crosswalk algorithm for France based on the individual responses to the 5 EQ-5D-5L domains ranging from -0.530 to 1.000. The smallest change considered clinically meaningful, is defined as a score difference of 0.08 points.

    Measured: Post Dose Month 24

  19. Number of Intensive Care Unit (ICU) Inpatient Days and Non-ICU Inpatient Days and Reasons for Hospitalization

    Length of initial ICU and non-ICU stay from liso-cel administration

    Measured: From first hospitalization to the last. Approximately 31 days

  20. Number of Participants Who Received Transfusions

    Number of participants who received transfusions

    Measured: From first dose to end of treatment period approximately 24 months

  21. Number of Participants Requiring Growth Factor Support.

    Growth factor support was defined as concomitant administration of FILGRASTIM, TBO FILGRASTIM, PEGFILGRASTIM, FILGRASTIM SNDZ, or FILGRASTIM AAFI.

    Measured: From first dose to end of treatment period approximately 24 months

  22. Number of Participants Requiring Intravenous Immunoglobulin (IVIG) Support

    Number of participants requiring intravenous immunoglobulin (IVIG) support

    Measured: From first dose to end of treatment period approximately 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Nov 2018
  2. Study start29 Nov 2018
  3. Primary completion22 Sep 2023
  4. Study completion22 Sep 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
104 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03744676
Sponsor's protocol ID
017007
Status last verified
Feb 2025
First submitted
7 Nov 2018
Last updated
27 Feb 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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/

Publications

  • Linhares Y, Freytes CO, Cherry M, Bachier C, Maris M, Hoda D, Varela JC, Bellomo C, Cross S, Essell J, Fanning S, Terebelo H, Yimer H, Courtright J, Sharman JP, Kostic A, Vedal M, Ogasawara K, Avilion A, Espinola R, Yuan B, Mattar B. OUTREACH: phase 2 study of lisocabtagene maraleucel as outpatient or inpatient treatment at community sites for R/R LBCL. Blood Adv. 2024 Dec 10;8(23):6114-6126. doi: 10.1182/bloodadvances.2024013254.

    PubMed 39347584

  • Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.

    PubMed 34515338

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing lisocabtagene maraleucel in people with Lymphoma, Non-Hodgkin and Lymphoma, run by Juno Therapeutics, a Subsidiary of Celgene at 23 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Cytokine Release Syndrome (CRS) Adverse Events Grade ≥ 3 (time frame: From first dose to 90 days following first dose (up to approximately 90 days)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03744676, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2025.

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