This is a Phase 2, open-label, multicenter study to determine the efficacy and safety of lisocabtagene maraleucel (JCAR017) in adult subjects who have relapsed from, or are refractory to, a single line of immunochemotherapy for aggressive B-cell non-Hodgkin lymphoma (NHL) and are ineligible for hematopoietic stem cell transplant (based on age, performance status, and/or comorbidities). Subjects will receive treatment with lisocabtagene maraleucel and will be followed for 2 years for safety, pharmacokinetics and biomarkers, disease status, quality of life, and survival.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
74
lisocabtagene maraleucel will be administered as a single dose intravenous (IV) injection
Banner MD Anderson Cancer Center
Gilbert, Arizona, United States
Local Institution - 0043
Gilbert, Arizona, United States
Scripps Clinic
La Jolla, California, United States
UNC School of Medicine
Los Angeles, California, United States
University of California Los Angeles
Los Angeles, California, United States
Overall Response Rate (ORR)
Overall response rate is the percent of participants with a best overall response (BOR) of either complete response (CR) or partial reasons (PR) based on the Independent Review Committee (IRC) assessment recorded from the time of JCAR017 treatment until disease progression, end of study, the start of another anticancer therapy or JCAR017 retreatment. CR = Score 1, 2, or 3 with or without a residual mass on the positron emission tomography 5-point scale (PET 5PS). A score of 3 in many patients indicates a good prognosis with standard treatment. PR = Score 4 or 5b with reduced uptake compared with baseline and residual mass(es) of any size. PET 5PS = 1- no uptake above background; 2- uptake ≤ mediastinum; 3- uptake \> mediastinum but ≤ liver; 4- uptake moderately \> liver; 5- uptake markedly higher than liver and/or new lesions; X- new areas of uptake unlikely to be related to lymphoma.
Time frame: From first dose to disease progression, end of study, the start of another anticancer therapy, or hematopoietic stem cell transplantation (up to approximately 24 months)
Number of Participants With Any Treatment-Emergent Adverse Events (TEAEs)
A TEAE was defined as an adverse event that started any time from initiation of product administration through and including 90 days following product administration. AEs that occurred after the initiation of subsequent anticancer therapy or product retreatment were not considered as product TEAE. AEs are graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (Version 4.03) (NCI CTCAE) guidelines where Grade 3= Severe, Grade 4= Life-threatening, and 5 = Death.
Time frame: From first dose to 90 days following first dose (up to approximately 90 days)
Change From Baseline of Hematology Laboratory Results: Hemoglobin
Change from baseline in Hematology laboratory analysis. Includes Hemoglobin. Baseline is the last observation collected prior to or on the date of product infusion.
Time frame: Baseline and Day 29
Change From Baseline of Hematology Laboratory Results: Leukocytes, Lymphocytes, Neutrophils, Platelets
Change from baseline in Hematology laboratory analysis. Includes Leukocytes, Lymphocytes, Neutrophils, and Platelets. Baseline is the last observation collected prior to or on the date of product infusion.
Time frame: Baseline and Day 29
Change From Baseline of Chemistry Laboratory Results: Albumin
Change from baseline in Chemistry laboratory analysis. Includes Albumin. Baseline is the last observation collected prior to or on the date of product infusion.
Time frame: Baseline and Day 29
Change From Baseline of Chemistry Laboratory Results: Alanine Aminotransferase, Aspartate Aminotransferase, Lactate Dehydrogenase
Change from baseline in Chemistry laboratory analysis. Includes Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase. Baseline is the last observation collected prior to or on the date of product infusion.
Time frame: Baseline and Day 29
Change From Baseline of Chemistry Laboratory Results: Bilirubin, Creatinine, Direct Bilirubin, Urate
Change from baseline in Chemistry laboratory analysis. Includes Bilirubin, Creatinine, Direct Bilirubin, and Urate. Baseline is the last observation collected prior to or on the date of product infusion.
Time frame: Baseline and Day 29
Change From Baseline of Chemistry Laboratory Results: Calcium Corrected, Magnesium, Phosphate, Potassium, Sodium
Change from baseline in Chemistry laboratory analysis. Includes Calcium Corrected, Magnesium, Phosphate, Potassium, and Sodium. Baseline is the last observation collected prior to or on the date of product infusion.
Time frame: Baseline and Day 29
Complete Response (CR) Rate
Complete response rate (CRR) was defined as the percent of participants with a best overall response (BOR) of complete response (CR) based on the Independent Review Committee (IRC) assessment recorded from the time of JCAR017 treatment until disease progression, end of study, the start of another anticancer therapy or JCAR017 retreatment. CR = Score 1, 2, or 3 with or without a residual mass on the positron emission tomography 5-point scale (PET 5PS). A score of 3 in many patients indicates a good prognosis with standard treatment. PET 5PS = 1- no uptake above background; 2- uptake ≤ mediastinum; 3- uptake \> mediastinum but ≤ liver; 4- uptake moderately \> liver; 5- uptake markedly higher than liver and/or new lesions; X- new areas of uptake unlikely to be related to lymphoma.
Time frame: From first dose to disease progression, end of study, the start of another anticancer therapy, or hematopoietic stem cell transplant (up to approximately 24 months)
Duration of Response (DOR)
Duration of response (DOR) is defined as the time from first complete response(CR) or partial response (PR) to progressive disease (PD) or death, whichever occurred first. CR = Score 1, 2, or 3 on the positron emission tomography 5-point scale (PET 5PS). A score of 3 indicates a good prognosis with standard treatment. PR = Score 4 or 5b with reduced uptake compared with baseline and residual mass(es) of any size. PD = Score 4 or 5b on PET 5PS with an increase in intensity of uptake from baseline and/or new fluorodeoxyglucose-avid foci consistent with lymphoma at interim or end-of-treatment assessment. PET 5PS = 1-no uptake above background; 2-uptake ≤ mediastinum; 3-uptake \> mediastinum but ≤ liver; 4-uptake moderately \> liver; 5-uptake markedly higher than liver and/or new lesions; X- new areas of uptake unlikely to be related to lymphoma.
Time frame: From first dose to up to approximately 24 months
Duration of Response (DOR) in Participants With Complete Response (CR)
DOR for participants with a best overall response of CR was defined as the time from documentation of first response (or CR) to progressive disease (PD) or death, whichever occurred first. The first documentation of CR/PR is the latest of all dates of required measurements to establish the response. The progression date is the earliest date of all assessments that led to a response assessment of PD. CR = Score 1, 2, or 3 on the positron emission tomography 5-point scale (PET 5PS). A score of 3 indicates a good prognosis with standard treatment. PD = Score 4 or 5b on PET 5PS with an increase in intensity of uptake from baseline and/or new fluorodeoxyglucose-avid foci consistent with lymphoma at interim or end-of-treatment assessment. PET 5PS = 1-no uptake above background; 2-uptake ≤ mediastinum; 3-uptake \> mediastinum but ≤ liver; 4-uptake moderately \> liver; 5-uptake markedly higher than liver and/or new lesions; X- new areas of uptake unlikely to be related to lymphoma.
Time frame: From first dose to up to approximately 24 months
Progression-Free Survival (PFS)
PFS is defined as the time from JCAR017 infusion to progressive disease (PD) or death. Kaplan-Meier (KM) methodology will be used to analyze PFS. PD = Score 4 or 5b on the positron emission tomography 5-point scale (PET 5PS) with an increase in intensity of uptake from baseline and/or new fluorodeoxyglucose-avid foci consistent with lymphoma at interim or end-of-treatment assessment. PET 5PS = 1- no uptake above background; 2- uptake ≤ mediastinum; 3- uptake \> mediastinum but ≤ liver; 4- uptake moderately \> liver; 5- uptake markedly higher than liver and/or new lesions; X- new areas of uptake unlikely to be related to lymphoma.
Time frame: From first dose to progressive disease (PD) or death (up to approximately 24 months)
Event-Free Survival (EFS)
EFS is defined as the time from JCAR017 infusion to the earliest of the following events: death from any cause, progressive disease (PD), or starting a new anticancer therapy. Kaplan-Meier (KM) methodology will be used to analyze EFS. PD = Score 4 or 5b on PET 5PS with an increase in intensity of uptake from baseline and/or new fluorodeoxyglucose-avid foci consistent with lymphoma at interim or end-of-treatment assessment. PET 5PS = 1-no uptake above background; 2-uptake ≤ mediastinum; 3-uptake \> mediastinum but ≤ liver; 4-uptake moderately \> liver; 5-uptake markedly higher than liver and/or new lesions; X- new areas of uptake unlikely to be related to lymphoma.
Time frame: From first dose to death from any cause, progressive disease (PD), or starting a new anticancer therapy (up to approximately 24 months)
Overall Survival (OS)
OS is defined as the time from JCAR017 infusion to the date of death. Kaplan-Meier (KM) methodology will be used to analyze OS.
Time frame: From first dose to date of death (up to approximately 24 months)
PK Parameters of JCAR017 in Blood as Assessed by qPCR: Cmax
Pharmacokinetic (PK) analyses were based on quantitative polymerase chain reaction (qPCR). Cmax = Maximum observed blood concentration.
Time frame: From first dose to up to 24 months
PK Parameters of JCAR017 in Blood as Assessed by qPCR: Tmax
Pharmacokinetic (PK) analyses were based on quantitative polymerase chain reaction (qPCR). Tmax = Time of maximum observed blood concentration.
Time frame: From first dose to up to 24 months
PK Parameters of JCAR017 in Blood as Assessed by qPCR: AUC (0-28)
Pharmacokinetic (PK) analyses were based on quantitative polymerase chain reaction (qPCR). AUC (0-28) = Area under the curve for concentration.
Time frame: From first dose to up to 24 months
Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Fatigue Subscale
* Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. * 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 10-point change in the scoring is considered to be a meaningful change in HRQoL. * Symptom scale/item higher score represents a high level of symptomatic problem.
Time frame: Baseline and Day 29
Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Physical Functioning Subscale
* Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. * 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 10-point change in the scoring is considered to be a meaningful change in HRQoL. * Functional scale and global health status/HRQoL higher scale score represents a higher level of well-being and better ability of daily functioning.
Time frame: Baseline and Day 29
Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Cognitive Functioning Subscale
* Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. * 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 10-point change in the scoring is considered to be a meaningful change in HRQoL. * Functional scale and global health status/HRQoL higher scale score represents a higher level of well-being and better ability of daily functioning.
Time frame: Baseline and Day 29
Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Global Health/QoL Subscale
* Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. * 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 10-point change in the scoring is considered to be a meaningful change in HRQoL. * Functional scale and global health status/HRQoL higher scale score represents a higher level of well-being and better ability of daily functioning.
Time frame: Baseline and Day 29
Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Role Functioning Subscale
* Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. * 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 10-point change in the scoring is considered to be a meaningful change in HRQoL. * Functional scale and global health status/HRQoL higher scale score represents a higher level of well-being and better ability of daily functioning.
Time frame: Baseline and Day 29
Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Emotional Functioning Subscale
* Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. * 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 10-point change in the scoring is considered to be a meaningful change in HRQoL. * Functional scale and global health status/HRQoL higher scale score represents a higher level of well-being and better ability of daily functioning.
Time frame: Baseline and Day 29
Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Social Functioning Subscale
* Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. * 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 10-point change in the scoring is considered to be a meaningful change in HRQoL. * Functional scale and global health status/HRQoL higher scale score represents a higher level of well-being and better ability of daily functioning.
Time frame: Baseline and Day 29
Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Pain Subscale
* Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. * 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 10-point change in the scoring is considered to be a meaningful change in HRQoL. * Symptom scale/item higher score represents a high level of symptomatic problem.
Time frame: Baseline and Day 29
Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Nausea/Vomiting Subscale
* Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. * 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 10-point change in the scoring is considered to be a meaningful change in HRQoL. * Symptom scale/item higher score represents a high level of symptomatic problem.
Time frame: Baseline and Day 29
Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Constipation Subscale
* Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. * 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 10-point change in the scoring is considered to be a meaningful change in HRQoL. * Symptom scale/item higher score represents a high level of symptomatic problem.
Time frame: Baseline and Day 29
Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Diarrhea Subscale
* Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. * 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 10-point change in the scoring is considered to be a meaningful change in HRQoL. * Symptom scale/item higher score represents a high level of symptomatic problem.
Time frame: Baseline and Day 29
Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Insomnia Subscale
* Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. * 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 10-point change in the scoring is considered to be a meaningful change in HRQoL. * Symptom scale/item higher score represents a high level of symptomatic problem.
Time frame: Baseline and Day 29
Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Dyspnea Subscale
* Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. * 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 10-point change in the scoring is considered to be a meaningful change in HRQoL. * Symptom scale/item higher score represents a high level of symptomatic problem.
Time frame: Baseline and Day 29
Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Appetite Loss Subscale
* Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. * 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 10-point change in the scoring is considered to be a meaningful change in HRQoL. * Symptom scale/item higher score represents a high level of symptomatic problem.
Time frame: Baseline and Day 29
Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Financial Difficulties Subscale
* Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. * 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 10-point change in the scoring is considered to be a meaningful change in HRQoL. * Functional scale and global health status/HRQoL higher scale score represents a higher level of well-being and better ability of daily functioning.
Time frame: Baseline and Day 29
Health-Related Quality of Life (HRQoL) Assessed by the FACT-Lym Subscale
The Functional Assessment of Cancer Treatment-Lymphoma (FACT-Lym) consists of the FACT-General scale and a 15-item lymphoma-specific additional concerns subscale (LYM). This scale addresses symptoms and functional limitations that are important to lymphoma patients. The LYM items are scored on a 0 ("Not at all") to 4 ("Very much") response scale. Items are aggregated to a single score on a 0-60 scale.
Time frame: Baseline and Day 29
Health-Related Quality of Life (HRQoL) Assessed by the 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. These health states are converted to a single index value using the crosswalk method to the EQ-5D-3L value set from the United Kingdom (UK). The EQ-5D-5L health states ranged from -.594 for the worst (55555) to 1 for the best (11111) for UK value set with an optimal health state is assigned a score of 1.00, death is assigned a score of 0.00 and negative values representing values as worse than dead. A change of .08 is considered to be a clinically meaningful change in health utility.
Time frame: Baseline and Day 29
Numbers of Intensive Care Unit (ICU) Inpatient Days
The numbers of ICU inpatient days.
Time frame: From first dose after JCAR017 infusion to up to approximately 24 months
Numbers of Non-intensive Care Unit (ICU) Inpatient Days
Number of non-ICU inpatient days.
Time frame: From first dose after JCAR017 infusion to up to approximately 24 months
The Number of Participants That Were Hospitalized For Adverse Events, Prophylaxis, Other
Length of hospitalization stay was reported for up to 24 months post liso-cel infusion. Reasons for hospitalization include adverse events, prophylaxis, and other. Adverse events were reported for up to 90 days post liso-cel infusion.
Time frame: From first dose after JCAR017 infusion to up to approximately 24 months
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