Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Mantle-Cell

Lymphoma, Follicular

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Mantle Cell Lymphoma

Follicular Lymphoma

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Each cycle of JCAR017 (lisocabtagene maraleucel) will be administered as 1 intravenous (IV) injection

Each cycle of JCAR017 (lisocabtagene maraleucel) will be administered as 2 intravenous (IV) injections

Participants will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of JCAR017. During JCAR017 production, participants may receive low-dose chemotherapy for disease control. Upon successful generation of JCAR017 product, participants will receive treatment with JCAR017 therapy. Treatment will include lymphodepleting chemotherapy followed by one dose of JCAR017 administered by intravenous (IV) injection.

JCAR017 (lisocabtagene maraleucel) single-dose schedule

Participants will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of JCAR017. During JCAR017 production, participants may receive low-dose chemotherapy for disease control. Upon product availability, participants will receive study treatment consisting of lymphodepleting chemotherapy followed by two IV doses of JCAR017.

JCAR017 (lisocabtagene maraleucel) 2-dose schedule

Bristol-Myers Squibb

This open-label Phase 1 study will evaluate the safety, PK, and antitumor activity of modified T cells (JCAR017) administered to adult patients with relapsed or refractory B-cell NHL. The dose and schedule of JCAR017 will be evaluated and modified, as needed, for safety and antitumor activity. We will also determine how long the modified T cells stay in the patient's body and how well JCAR017 works in treating patients with non-Hodgkin's lymphoma whose disease has come back or has not responded to treatment.

This is an open-label, multicenter Phase 1 study to determine the safety, pharmacokinetics (PK), and antitumor activity of JCAR017 in adult patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), follicular lymphoma Grade 3B, and mantle cell lymphoma (MCL). This study will evaluate and refine the dose and schedule of JCAR017 to optimize safety and antitumor activity. A dose-confirmation group or groups will further evaluate the safety and efficacy of JCAR017 at the recommended regimen(s).

Upon successful generation of JCAR017 product, participants will receive treatment with one or more cycles of JCAR017 therapy. Each cycle will include lymphodepleting chemotherapy followed by one or two doses of JCAR017 administered by intravenous (IV) injection.

The follow-up period for each participant is approximately 24 months after the final JCAR017 infusion. Long-term follow-up for survival, toxicity, and viral vector safety will continue under a separate long-term follow-up protocol per health regulatory authority guidelines, currently up to 15 years after the last JCAR017 infusion.

Study Evaluating the Safety and Pharmacokinetics of JCAR017 in B-cell Non-Hodgkin Lymphoma (TRANSCEND-NHL-001)

A Phase 1, Multicenter, Open-Label Study of JCAR017, CD19-targeted Chimeric Antigen Receptor (CAR) T Cells, for Relapsed and Refractory (R/R) B-cell Non-Hodgkin Lymphoma (NHL)

Juno Therapeutics, a Subsidiary of Celgene

All Drugs and Chemicals

Immunomodulating Agents

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.

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

lisocabtagene maraleucel

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.

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.

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

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/

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).

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.

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

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.

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.

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

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.

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

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.

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.

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, and anxiety/depression). Each dimension has 5 levels (no problems, slight problems, moderate problems, severe problems, and extreme problems).

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

The total number at risk for all-cause mortality represents all participants who underwent leukapheresis. The total number at risk by any serious adverse event and other (not including serious) adverse events represents all participants that received at least 1 dose of study medication (JCAR017).

Participants underwent leukapheresis and may receive salvage low- dose chemotherapy or one cycle of non-curative standard of care antitumor therapy if required. Eligible participants then received lymphodepleting chemotherapy with fludarabine and cyclophosphamide (flu/cy) followed by a single dose of JCAR017 (100×10\^6 CAR+ T cells/infusion) administered intravenously (IV) 2 to 7 days after completion of lymphodepleting chemotherapy.

Lisocabtagene Maraleucel (JCAR017)

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

White

Other

Unknown

Race/Ethnicity, Customized

Bristol-Myers Squibb Study Director

All participants who received at least one JCAR017 infusion

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

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

Percentage of Participants With Infection Adverse Events Grade ≥ 3

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

Number of Participants With Adverse Events

Number of Participants With Clinically Significant Laboratory Abnormalities- Hematology

Number of Participants With Clinically Significant Laboratory Abnormalities- Chemistry

Number of Participants With Adverse Events Grade ≥ 3

Time to Onset

Time to Resolution

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

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

Tocilizumab Only

Corticosteroid Only

Both Tocilizumab and Corticosteroid

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

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

Objective Response Rate (ORR)

Complete Response Rate (CRR)

DoCR

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

Progression Free Survival (PFS)

Overall Survival (OS)

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

Maximum Observed Blood Concentration (Cmax)

Time of Maximum Observed Blood Concentration (Tmax)

European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30

EuroQol Instrument EQ-5D-5L.

Initial ICU Stay

Initial Non-ICU Stay

Liso-cel-treated Analysis Set - Inpatient Monitored

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study Evaluating the Safety and Pharmacokinetics of JCAR017 in B-cell Non-Hodgkin Lymphoma (TRANSCEND-NHL-001)	NCT02631044	Non-Hodgkin Lym... Diffuse Large B... Follicular Lymp... Mantle-cell Lym... Primary Mediast...	JCAR017 (lisoca... JCAR017 (lisoca...	18 Years -	Juno Therapeutics, a Subsidiary of Celgene
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)	NCT03744676	Lymphoma, Non-H... Lymphoma Lymphoma, B-Cel... Lymphoma, Large... Neoplasms Neoplasms by Hi... Lymphoprolifera... Lymphatic Disea... Immunoprolifera... Immune System D...	lisocabtagene m...	18 Years -	Juno Therapeutics, a Subsidiary of Celgene
Study Evaluating the Safety and Pharmacokinetics of JCAR017 in B-cell Non-Hodgkin Lymphoma (TRANSCEND-NHL-001)	NCT02631044	Non-Hodgkin Lym... Diffuse Large B... Follicular Lymp... Mantle-cell Lym... Primary Mediast...	JCAR017 (lisoca... JCAR017 (lisoca...	18 Years -	Juno Therapeutics, a Subsidiary of Celgene

Spots Global Cancer Trial Database for autologous t cell therapy