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
Conditions
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
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.
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.
Interventions
BIOLOGICALlisocabtagene maraleucel
lisocabtagene maraleucel will be administered as single dose intravenous (IV) injection
Sponsors
Bristol-Myers Squibb
Juno Therapeutics, a Subsidiary of Celgene
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Cytokine Release Syndrome (CRS) Adverse Events Grade ≥ 3 | From first dose to 90 days following first dose (up to approximately 90 days) | 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). |
| Percentage of Participants With Neurotoxicity (NT) Adverse Events Grade ≥ 3 | From first dose to 90 days following first dose (up to approximately 90 days) | 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. |
| Percentage of Participants With Infection Adverse Events Grade ≥ 3 | From first dose to 90 days following first dose (up to approximately 90 days) | Incidence of treatment-emergent Grade ≥ 3 infections, defined using MedDRA SOC. |
| Percentage of Participants With Grade ≥ 3 Prolonged Cytopenia at Day 29. | At Day 29 after first treatment | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events Grade ≥ 3 | From first dose to 90 days following first dose (up to approximately 90 days) | — |
| Time to Onset and Time to Resolution of Grade ≥ 3 Cytokine Release Syndrome (CRS) | From first dose to up to approximately 41 months | — |
| Time to Onset and Time to Resolution of Grade ≥ 3 Neurotoxicity (NT) | From first dose to up to approximately 41 months | — |
| Number of Participants Administered Tocilizumab and Corticosteroid for Management of Cytokine Release Syndrome (CRS) | From first dose to up to approximately 41 months | — |
| Number of Participants Administered Tocilizumab and Corticosteroid for Management of Neurotoxicity (NT) | From first dose to up to study completion (Approximately 57 Months and 24 days) | — |
| Objective Response Rate (ORR) | From first dose to up to approximately 41 months | 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. |
| Complete Response Rate (CRR) | From first dose to up to approximately 41 months | 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) and Duration of Complete Response (DoCR) | From first dose to up to approximately 41 months | 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 (PFS) | From first dose to up to study completion (Approximately 57 Months and 24 days) | 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 |
| Time of Maximum Observed Blood Concentration (Tmax) | 28days after first dose | — |
| Area Under the Blood Concentration-time Curve From Time to Zero to 28 Days After Dosing AUC (0-28) | 28days after first dose | — |
| Maximum Observed Blood Concentration (Cmax) | 28days after first dose | — |
| Mean Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 | From Enrollment to end of follow up, approximately 26 months | 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. |
| Mean Change From Baseline in EuroQol Instrument EQ-5D-5L. | Post Dose Month 24 | 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. |
| Number of Intensive Care Unit (ICU) Inpatient Days and Non-ICU Inpatient Days and Reasons for Hospitalization | From first hospitalization to the last. Approximately 31 days | Length of initial ICU and non-ICU stay from liso-cel administration |
| Number of Participants Who Received Transfusions | From first dose to end of treatment period approximately 24 months | Number of participants who received transfusions |
| Number of Participants Requiring Growth Factor Support. | From first dose to end of treatment period approximately 24 months | Growth factor support was defined as concomitant administration of FILGRASTIM, TBO FILGRASTIM, PEGFILGRASTIM, FILGRASTIM SNDZ, or FILGRASTIM AAFI. |
| Number of Participants Requiring Intravenous Immunoglobulin (IVIG) Support | From first dose to end of treatment period approximately 24 months | Number of participants requiring intravenous immunoglobulin (IVIG) support |
| Overall Survival (OS) | From first dose to up to study completion (Approximately 57 Months and 24 days) | 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. |
| Number of Participants With Adverse Events | From first dose to 90 days following first dose (up to approximately 90 days) | — |
| Number of Participants With Clinically Significant Laboratory Abnormalities- Hematology | From first dose to up to 41 months | — |
| Number of Participants With Clinically Significant Laboratory Abnormalities- Chemistry | From first dose to up to 41 months | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lisocabtagene Maraleucel (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. | 104 |
| Total | 104 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Pre-Treatment Phase | Death | 7 |
| Pre-Treatment Phase | Disease related complications | 2 |
| Pre-Treatment Phase | No longer meets study criteria | 4 |
| Pre-Treatment Phase | Other Reasons | 7 |
| Treatment Phase | Death | 33 |
| Treatment Phase | other reasons | 6 |
| Treatment Phase | Participant withdrew consent | 8 |
Baseline characteristics
| Characteristic | Lisocabtagene Maraleucel (JCAR017) |
|---|---|
| Age, Continuous | 64.9 Years STANDARD_DEVIATION 11.61 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 77 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 8 Participants |
| Race/Ethnicity, Customized Other | 7 Participants |
| Race/Ethnicity, Customized Unknown | 9 Participants |
| Race/Ethnicity, Customized White | 88 Participants |
| Sex: Female, Male Female | 38 Participants |
| Sex: Female, Male Male | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 48 / 82 |
| other Total, other adverse events | 82 / 82 |
| serious Total, serious adverse events | 48 / 82 |
Outcome results
Primary
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).
Time frame: From first dose to 90 days following first dose (up to approximately 90 days)
Population: All participants who received at least one JCAR017 infusion
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lisocabtagene Maraleucel (JCAR017) | Percentage of Participants With Cytokine Release Syndrome (CRS) Adverse Events Grade ≥ 3 | 0.0 Percentage of participants |
Primary
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.
Time frame: At Day 29 after first treatment
Population: All participants who received at least one JCAR017 infusion
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lisocabtagene Maraleucel (JCAR017) | Percentage of Participants With Grade ≥ 3 Prolonged Cytopenia at Day 29. | 32.9 Percentage of participants |
Primary
Percentage of Participants With Infection Adverse Events Grade ≥ 3
Incidence of treatment-emergent Grade ≥ 3 infections, defined using MedDRA SOC.
Time frame: From first dose to 90 days following first dose (up to approximately 90 days)
Population: All participants who received at least one JCAR017 infusion
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lisocabtagene Maraleucel (JCAR017) | Percentage of Participants With Infection Adverse Events Grade ≥ 3 | 11.0 Percentage of participants |
Primary
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.
Time frame: From first dose to 90 days following first dose (up to approximately 90 days)
Population: All participants who received at least one JCAR017 infusion
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lisocabtagene Maraleucel (JCAR017) | Percentage of Participants With Neurotoxicity (NT) Adverse Events Grade ≥ 3 | 9.8 Percentage of participants |
Secondary
Area Under the Blood Concentration-time Curve From Time to Zero to 28 Days After Dosing AUC (0-28)
Time frame: 28days after first dose
Population: qPCR PK Analysis Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Lisocabtagene Maraleucel (JCAR017) | Area Under the Blood Concentration-time Curve From Time to Zero to 28 Days After Dosing AUC (0-28) | 219760.3 day*copies/μg | Geometric Coefficient of Variation 216.1 |
Secondary
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
Time frame: From first dose to up to approximately 41 months
Population: All participants who received at least one JCAR017 infusion
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lisocabtagene Maraleucel (JCAR017) | Complete Response Rate (CRR) | 53.7 Percentage of Participants |
Secondary
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.
Time frame: From first dose to up to approximately 41 months
Population: All participants who received at least one JCAR017 infusion
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lisocabtagene Maraleucel (JCAR017) | Duration of Response (DoR) and Duration of Complete Response (DoCR) | DoR | 14.75 Months |
| Lisocabtagene Maraleucel (JCAR017) | Duration of Response (DoR) and Duration of Complete Response (DoCR) | DoCR | NA Months |
Secondary
Maximum Observed Blood Concentration (Cmax)
Time frame: 28days after first dose
Population: qPCR PK Analysis Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Lisocabtagene Maraleucel (JCAR017) | Maximum Observed Blood Concentration (Cmax) | 24077.8 copies/μg | Geometric Coefficient of Variation 230.7 |
Secondary
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.
Time frame: From Enrollment to end of follow up, approximately 26 months
Population: JCAR017 All treated participants with a measurement at post dose month 24
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lisocabtagene Maraleucel (JCAR017) | Mean Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 | Emotional Functioning | 2.7 Scores on a Scale | Standard Deviation 20.31 |
| Lisocabtagene Maraleucel (JCAR017) | Mean Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 | Fatigue | -14.6 Scores on a Scale | Standard Deviation 21.24 |
| Lisocabtagene Maraleucel (JCAR017) | Mean Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 | Financial Difficulties | -9.1 Scores on a Scale | Standard Deviation 25.58 |
| Lisocabtagene Maraleucel (JCAR017) | Mean Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 | Global Health Stuats/QoL | 15.2 Scores on a Scale | Standard Deviation 21.61 |
| Lisocabtagene Maraleucel (JCAR017) | Mean Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 | Insomnia | -10.6 Scores on a Scale | Standard Deviation 27.96 |
| Lisocabtagene Maraleucel (JCAR017) | Mean Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 | Nausea and Vomiting | -9.8 Scores on a Scale | Standard Deviation 17.56 |
| Lisocabtagene Maraleucel (JCAR017) | Mean Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 | Pain | -13.6 Scores on a Scale | Standard Deviation 26.55 |
| Lisocabtagene Maraleucel (JCAR017) | Mean Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 | Physical Functioning | 2.4 Scores on a Scale | Standard Deviation 16.14 |
| Lisocabtagene Maraleucel (JCAR017) | Mean Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 | Role Functioning | 12.9 Scores on a Scale | Standard Deviation 23.53 |
| Lisocabtagene Maraleucel (JCAR017) | Mean Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 | Social Functioning | 17.4 Scores on a Scale | Standard Deviation 24.92 |
| Lisocabtagene Maraleucel (JCAR017) | Mean Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 | Apptetie Loss | -22.7 Scores on a Scale | Standard Deviation 23.87 |
| Lisocabtagene Maraleucel (JCAR017) | Mean Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 | Cognitive Functioning | 1.5 Scores on a Scale | Standard Deviation 18.48 |
| Lisocabtagene Maraleucel (JCAR017) | Mean Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 | Constipation | -7.6 Scores on a Scale | Standard Deviation 27.08 |
| Lisocabtagene Maraleucel (JCAR017) | Mean Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 | Diarrhea | -3.0 Scores on a Scale | Standard Deviation 27.04 |
| Lisocabtagene Maraleucel (JCAR017) | Mean Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 | Dyspnea | 6.1 Scores on a Scale | Standard Deviation 13.16 |
Secondary
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.
Time frame: Post Dose Month 24
Population: All treated participants with an EQ-5D-5L index score post dose month 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lisocabtagene Maraleucel (JCAR017) | Mean Change From Baseline in EuroQol Instrument EQ-5D-5L. | 0.0 Score on a Scale | Standard Deviation 0.13 |
Secondary
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
Time frame: From first hospitalization to the last. Approximately 31 days
Population: Liso-cel-treated Analysis Set - Inpatient Monitored
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lisocabtagene Maraleucel (JCAR017) | Number of Intensive Care Unit (ICU) Inpatient Days and Non-ICU Inpatient Days and Reasons for Hospitalization | Initial Non-ICU Stay | 15.0 days |
| Lisocabtagene Maraleucel (JCAR017) | Number of Intensive Care Unit (ICU) Inpatient Days and Non-ICU Inpatient Days and Reasons for Hospitalization | Initial ICU Stay | 5.5 days |
Secondary
Number of Participants Administered Tocilizumab and Corticosteroid for Management of Cytokine Release Syndrome (CRS)
Time frame: From first dose to up to approximately 41 months
Population: All participants who received at least one JCAR017 infusion
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lisocabtagene Maraleucel (JCAR017) | Number of Participants Administered Tocilizumab and Corticosteroid for Management of Cytokine Release Syndrome (CRS) | Tocilizumab Only | 7 Participants |
| Lisocabtagene Maraleucel (JCAR017) | Number of Participants Administered Tocilizumab and Corticosteroid for Management of Cytokine Release Syndrome (CRS) | Corticosteroid Only | 2 Participants |
| Lisocabtagene Maraleucel (JCAR017) | Number of Participants Administered Tocilizumab and Corticosteroid for Management of Cytokine Release Syndrome (CRS) | Both Tocilizumab and Corticosteroid | 7 Participants |
Secondary
Number of Participants Administered Tocilizumab and Corticosteroid for Management of Neurotoxicity (NT)
Time frame: From first dose to up to study completion (Approximately 57 Months and 24 days)
Population: All participants who received at least one JCAR017 infusion
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lisocabtagene Maraleucel (JCAR017) | Number of Participants Administered Tocilizumab and Corticosteroid for Management of Neurotoxicity (NT) | Tocilizumab Only | 0 Participants |
| Lisocabtagene Maraleucel (JCAR017) | Number of Participants Administered Tocilizumab and Corticosteroid for Management of Neurotoxicity (NT) | Corticosteroid Only | 12 Participants |
| Lisocabtagene Maraleucel (JCAR017) | Number of Participants Administered Tocilizumab and Corticosteroid for Management of Neurotoxicity (NT) | Both Tocilizumab and Corticosteroid | 1 Participants |
Secondary
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.
Time frame: From first dose to end of treatment period approximately 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lisocabtagene Maraleucel (JCAR017) | Number of Participants Requiring Growth Factor Support. | 35 Participants |
Secondary
Number of Participants Requiring Intravenous Immunoglobulin (IVIG) Support
Number of participants requiring intravenous immunoglobulin (IVIG) support
Time frame: From first dose to end of treatment period approximately 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lisocabtagene Maraleucel (JCAR017) | Number of Participants Requiring Intravenous Immunoglobulin (IVIG) Support | 12 Participants |
Secondary
Number of Participants Who Received Transfusions
Number of participants who received transfusions
Time frame: From first dose to end of treatment period approximately 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lisocabtagene Maraleucel (JCAR017) | Number of Participants Who Received Transfusions | 43 Participants |
Secondary
Number of Participants With Adverse Events
Time frame: From first dose to 90 days following first dose (up to approximately 90 days)
Population: All participants who received at least one JCAR017 infusion
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lisocabtagene Maraleucel (JCAR017) | Number of Participants With Adverse Events | 82 Participants |
Secondary
Number of Participants With Adverse Events Grade ≥ 3
Time frame: From first dose to 90 days following first dose (up to approximately 90 days)
Population: All participants who received at least one JCAR017 infusion
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lisocabtagene Maraleucel (JCAR017) | Number of Participants With Adverse Events Grade ≥ 3 | 61 Participants |
Secondary
Number of Participants With Clinically Significant Laboratory Abnormalities- Chemistry
Time frame: From first dose to up to 41 months
Population: All participants who received at least one JCAR017 infusion
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lisocabtagene Maraleucel (JCAR017) | Number of Participants With Clinically Significant Laboratory Abnormalities- Chemistry | 0 Participants |
Secondary
Number of Participants With Clinically Significant Laboratory Abnormalities- Hematology
Time frame: From first dose to up to 41 months
Population: All participants who received at least one JCAR017 infusion
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lisocabtagene Maraleucel (JCAR017) | Number of Participants With Clinically Significant Laboratory Abnormalities- Hematology | 0 Participants |
Secondary
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.
Time frame: From first dose to up to approximately 41 months
Population: All participants who received at least one JCAR017 infusion
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lisocabtagene Maraleucel (JCAR017) | Objective Response Rate (ORR) | 80.5 Percentage of Participants |
Secondary
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.
Time frame: From first dose to up to study completion (Approximately 57 Months and 24 days)
Population: All participants who received at least one JCAR017 infusion
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lisocabtagene Maraleucel (JCAR017) | Overall Survival (OS) | 21.88 Months |
Secondary
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
Time frame: From first dose to up to study completion (Approximately 57 Months and 24 days)
Population: All participants who received at least one JCAR017 infusion
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lisocabtagene Maraleucel (JCAR017) | Progression Free Survival (PFS) | 5.86 Months |
Secondary
Time of Maximum Observed Blood Concentration (Tmax)
Time frame: 28days after first dose
Population: qPCR PK Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lisocabtagene Maraleucel (JCAR017) | Time of Maximum Observed Blood Concentration (Tmax) | 10.0 days |
Secondary
Time to Onset and Time to Resolution of Grade ≥ 3 Cytokine Release Syndrome (CRS)
Time frame: From first dose to up to approximately 41 months
Population: All participants who received at least one JCAR017 infusion
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lisocabtagene Maraleucel (JCAR017) | Time to Onset and Time to Resolution of Grade ≥ 3 Cytokine Release Syndrome (CRS) | Time to Onset | 0 Days |
| Lisocabtagene Maraleucel (JCAR017) | Time to Onset and Time to Resolution of Grade ≥ 3 Cytokine Release Syndrome (CRS) | Time to Resolution | 0 Days |
Secondary
Time to Onset and Time to Resolution of Grade ≥ 3 Neurotoxicity (NT)
Time frame: From first dose to up to approximately 41 months
Population: All participants who received at least one JCAR017 infusion
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lisocabtagene Maraleucel (JCAR017) | Time to Onset and Time to Resolution of Grade ≥ 3 Neurotoxicity (NT) | Time to Onset | 9.5 Days |
| Lisocabtagene Maraleucel (JCAR017) | Time to Onset and Time to Resolution of Grade ≥ 3 Neurotoxicity (NT) | Time to Resolution | 16.5 Days |