NCT03484702 · REGISTRY CONDITION SEARCH

Trial to Determine the Efficacy and Safety of JCAR017 in Adult Participants With Aggressive B-Cell Non-Hodgkin Lymphoma

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE2
Status at capture: COMPLETED
Registry last update: 2024-12-27

The purpose of this study is to evaluate the efficacy and safety of JCAR017 in participants with aggressive B-cell non-Hodgkin lymphoma (B-NHL)

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Overall Response Rate (ORR) Per Independent Review Committee in Cohorts 1, 2 and 3

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outcome · POSTED

Overall Response Rate (ORR) Per Investigator in Cohort 4

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outcome · POSTED

Overall Response Rate (ORR) Per Investigator in Cohort 5

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outcome · POSTED

Number of Participants With Adverse Events in Cohort 7

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outcome · POSTED

Number of Participants With Serious Adverse Events (SAEs) in Cohort 7

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outcome · POSTED

Number of Participants With Increase From Baseline in Select Hematology Parameters - Cohort 7

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outcome · POSTED

Number of Participants With Increase From Baseline in Select Serum Chemistry Parameters - Cohort 7

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outcome · POSTED

Number of Participants With Adverse Events in Cohorts 1, 2, 3, 4, and 5

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outcome · POSTED

Number of Participants With Serious Adverse Events (SAEs) in Cohorts 1, 2, 3, 4, and 5

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outcome · POSTED

Number of Participants With Increase From Baseline in Select Hematology Parameters - Cohorts 1, 2, 3, 4, and 5

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outcome · POSTED

Number of Participants With Increase From Baseline in Select Serum Chemistry Parameters - Cohorts 1, 2, 3, 4, and 5

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outcome · POSTED

Overall Response Rate (ORR) in Cohort 7

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outcome · POSTED

Complete Response Rate (CRR)

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outcome · POSTED

Event Free Survival (EFS)

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outcome · POSTED

Progression Free Survival (PFS) Using European Medicines Agency (EMA) Criteria

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Duration of Response (DOR)

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outcome · POSTED

Maximum Concentration (Cmax) of JCAR017 by qPCR

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outcome · POSTED

Time to Peak Concentration (Tmax) of JCAR017 by qPCR

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outcome · POSTED

Total Exposure to JCAR017 as Measured by Area Under the Curve (AUC) of JCAR017 by qPCR

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outcome · POSTED

Percent of Participants With Presence of JCAR017 Transgene in Peripheral Blood by qPCR

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outcome · POSTED

Change From Baseline in European Organisation for Research and Treatment of Cancer - Quality of Life C30 Questionnaire (EORTC QLQ-C30) Scores

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outcome · POSTED

Change From Baseline in Functional Assessment of Cancer Treatment-Lymphoma "Additional Concerns" Subscale (FACT-LymS) Scores

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Histological confirmation of diagnosis at last relapse * Adequate organ function * Adequate vascular access for leukapheresis procedure Exclusion Criteria: * Prior history of malignancies, other than aggressive relapsed/refractory Non-Hodgkin Lymphoma, unless the participant has been in remission for ≥ 2 years with the exception of non-invasive malignancies * Received previous CD19-targeted therapy * Progressive vascular tumor invasion, thrombosis, or embolism Other protocol-defined inclusion/exclusion criteria apply
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

intervention Names
Drug: JCAR017
label
Administration of JCAR017
type
EXPERIMENTAL

interventions

arm Group Labels
Administration of JCAR017
description
Specified dose on specified days
name
JCAR017
other Names
Lisocabtagene Maraleucel (liso-cel)
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 113
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Overall response rate (ORR) by Independent Review Committee (Cohorts 1, 2, 3). ORR is the percent of participants with best overall response of complete response (CR) or partial response (PR). Complete response via PET-CT: * Lymph nodes/extralymphatic: Score 1, 2, 3a with/without residual mass on 5-point scale * New lesions: No * Bone marrow: No FDG-avid disease Complete response via CT scan: * Lymph nodes/extralymphatic: Target nodes/nodal masses ≤ 1.5 cm longest transverse diameter. * Nonmeasured lesion: No * New lesions: No * Bone marrow: Normal Partial response via PET-CT: * Lymph nodes/extralymphatic: Score 4, 5b, reduced uptake from baseline * New lesions: No * Bone marrow: Residual uptake higher than normal, reduced from baseline Partial response via CT scan: * Lymph nodes/extralymphatic: 50% decrease in sum of diameters of \<= 6 target measurable nodes/extranodal sites * Nonmeasured lesion: No * Organ enlargement: Spleen length decreased \> 50% * New lesions: No
measure
Overall Response Rate (ORR) Per Independent Review Committee in Cohorts 1, 2 and 3
time Frame
From JCAR017 infusion until disease progression, end of study, the start of another anticancer therapy, or hemopoietic stem cell transplant (HSCT) (up to approximately 63 months)
description
Overall response rate (ORR) is the percent of participants with best overall response of complete response (CR) or partial response (PR). Complete response via PET-CT: * Lymph nodes/extralymphatic: Score 1, 2, 3a with/without residual mass on 5-point scale * New lesions: No * Bone marrow: No FDG-avid disease Complete response via CT scan: * Lymph nodes/extralymphatic: Target nodes/nodal masses ≤ 1.5 cm longest transverse diameter. * Nonmeasured lesion: None * New lesions: No * Bone marrow: Normal Partial response via PET-CT: * Lymph nodes/extralymphatic: Score 4, 5b, reduced uptake from baseline * New lesions: None * Bone marrow: Residual uptake higher than normal, reduced from baseline Partial response via CT scan: * Lymph nodes/extralymphatic: 50% decrease in sum of diameters of \<= 6 target measurable nodes/extranodal sites * Nonmeasured lesion: None/normal * Organ enlargement: Spleen length decreased \> 50% * New lesions: No
measure
Overall Response Rate (ORR) Per Investigator in Cohort 4
time Frame
From JCAR017 infusion until disease progression, end of study, the start of another anticancer therapy, or hemopoietic stem cell transplant (HSCT) (up to approximately 63 months)
description
Overall response rate (ORR) determined by Investigator assessment after JCAR017 infusion. The ORR is the percent of participants with best overall response (BOR) of either complete response (CR), complete response unconfirmed (Cru) or partial response (PR). Complete response (CR): * Brain imaging: No contrast enhancement * Corticosteroid dose: None * Eye examination: Normal * Cerebrospinal fluid cytology: Negative Complete response unconfirmed (CRu): * Brain imaging: No contrast enhancement, Minimal abnormality * Corticosteroid dose: Any * Eye examination: Normal, minor RPE abnormality * Cerebrospinal fluid cytology: Negative Partial response (PR): * Brain imaging: 50% decrease in enhancing tumor, no contrast enhancement. * Corticosteroid dose: Irrelevant * Eye examination: Minor RPE abnormality, decrease in vitreous cells or retinal infiltrate. * Cerebrospinal fluid cytology: Negative, persistent or suspicious
measure
Overall Response Rate (ORR) Per Investigator in Cohort 5
time Frame
From JCAR017 infusion until disease progression, end of study, the start of another anticancer therapy, or hemopoietic stem cell transplant (HSCT) (up to approximately 63 months)
description
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening (i.e., any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE. Graded according to NCI CTCAE (Version 4.03) guidelines where grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life threatening, grade 5 = death.
measure
Number of Participants With Adverse Events in Cohort 7
time Frame
From leukapheresis to end of study (up to approximately 63 months)
description
A serious adverse event (SAE) is defined as any adverse event (AE) occurring at any dose that: * Results in death; * Is life-threatening (ie, in the opinion of the Investigator, the participant is at immediate risk of death from the AE); * Requires inpatient hospitalization or prolongation of existing hospitalization (hospitalization is defined as an inpatient admission, regardless of length of stay). * Results in persistent or significant disability/incapacity (a substantial disruption of the participant's ability to conduct normal life functions); * Is a congenital anomaly/birth defect; * Constitutes an important medical event. Graded according to NCI CTCAE (Version 4.03) guidelines where grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life threatening, grade 5 = death.
measure
Number of Participants With Serious Adverse Events (SAEs) in Cohort 7
time Frame
From leukapheresis to end of study (up to approximately 63 months)
description
JCAR017 treatment-emergent laboratory abnormalities are defined as an abnormality that, compared to baseline, worsens by at least one grade after JCAR017 infusion. The baseline value is defined as the last available recorded value on or prior to the date of JCAR017 infusion. Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe), Grade 4 (Life-threatening), Grade 5 (Death).
measure
Number of Participants With Increase From Baseline in Select Hematology Parameters - Cohort 7
time Frame
At Baseline and Day 29 after JCAR017 infusion
description
JCAR017 treatment-emergent laboratory abnormalities are defined as an abnormality that, compared to baseline, worsens by at least one grade after JCAR017 infusion. The baseline value is defined as the last available recorded value on or prior to the date of JCAR017 infusion. Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe), Grade 4 (Life-threatening), Grade 5 (Death).
measure
Number of Participants With Increase From Baseline in Select Serum Chemistry Parameters - Cohort 7
time Frame
At Baseline and Day 29 after JCAR017 infusion

secondary Outcomes

description
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening (i.e., any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE. Graded according to NCI CTCAE (Version 4.03) guidelines where grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life threatening, grade 5 = death.
measure
Number of Participants With Adverse Events in Cohorts 1, 2, 3, 4, and 5
time Frame
From leukapheresis to end of study (up to approximately 63 months)
description
A serious adverse event (SAE) is defined as any adverse event (AE) occurring at any dose that: * Results in death; * Is life-threatening (ie, in the opinion of the Investigator, the participant is at immediate risk of death from the AE); * Requires inpatient hospitalization or prolongation of existing hospitalization (hospitalization is defined as an inpatient admission, regardless of length of stay). * Results in persistent or significant disability/incapacity (a substantial disruption of the participant's ability to conduct normal life functions); * Is a congenital anomaly/birth defect; * Constitutes an important medical event. Graded according to NCI CTCAE (Version 4) guidelines where grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life threatening, grade 5 = death.
measure
Number of Participants With Serious Adverse Events (SAEs) in Cohorts 1, 2, 3, 4, and 5
time Frame
From leukapheresis to end of study (up to approximately 63 months)
description
JCAR017 treatment-emergent laboratory abnormalities are defined as an abnormality that, compared to baseline, worsens by at least one grade after JCAR017 infusion. The baseline value is defined as the last available recorded value on or prior to the date of JCAR017 infusion. Grade 1 = Mild, Grade 2 =Moderate, Grade 3 =Severe, Grade 4 =Life-threatening, Grade 5 =Death.
measure
Number of Participants With Increase From Baseline in Select Hematology Parameters - Cohorts 1, 2, 3, 4, and 5
time Frame
At Baseline and Day 29 after JCAR017 infusion
description
JCAR017 treatment-emergent laboratory abnormalities are defined as an abnormality that, compared to baseline, worsens by at least one grade after JCAR017 infusion. The baseline value is defined as the last available recorded value on or prior to the date of JCAR017 infusion. Grade 1 = Mild, Grade 2 =Moderate, Grade 3 =Severe, Grade 4 =Life-threatening, Grade 5 =Death.
measure
Number of Participants With Increase From Baseline in Select Serum Chemistry Parameters - Cohorts 1, 2, 3, 4, and 5
time Frame
At Baseline and Day 29 after JCAR017 infusion
description
ORR by Independent Review Committee. ORR is the percent of participants with best overall response of complete response (CR) or partial response (PR). Complete response via PET-CT: * Lymph nodes/extralymphatic: Score 1, 2, 3a with/without residual mass on 5-point scale * New lesions: No * Bone marrow: No FDG-avid disease Complete response via CT scan: * Lymph nodes/extralymphatic: Target nodes/nodal masses ≤ 1.5 cm longest transverse diameter. * Nonmeasured lesion: None * New lesions: No * Bone marrow: Normal Partial response via PET-CT: * Lymph nodes/extralymphatic: Score 4, 5b, reduced uptake from baseline * New lesions: None * Bone marrow: Residual uptake higher than normal, reduced from baseline Partial response via CT scan: * Lymph nodes/extralymphatic: 50% decrease in sum of diameters of \<= 6 target measurable nodes/extranodal sites * Nonmeasured lesion: None/normal * Organ enlargement: Spleen length decreased \> 50% * New lesions: No
measure
Overall Response Rate (ORR) in Cohort 7
time Frame
From JCAR017 infusion until disease progression, end of study, the start of another anticancer therapy, or hemopoietic stem cell transplant (HSCT) (up to approximately 63 months)
description
Complete response rate is defined as percentage of participants achieving a best overall response of complete response. Complete response via PET-CT: * Lymph nodes/extralymphatic: Score 1, 2, 3a with/without residual mass on 5-point scale * New lesions: No * Bone marrow: No FDG-avid disease Complete response via CT scan: * Lymph nodes/extralymphatic: Target nodes/nodal masses ≤ 1.5 cm longest transverse diameter. * Nonmeasured lesion: None * New lesions: No * Bone marrow: Normal Complete response (CR) (Cohort 5): * Brain imaging: No contrast enhancement * Corticosteroid dose: None * Eye examination: Normal * Cerebrospinal fluid cytology: Negative Complete response unconfirmed (CRu) (Cohort 5): * Brain imaging: No contrast enhancement, Minimal abnormality * Corticosteroid dose: Any * Eye examination: Normal, minor RPE abnormality * Cerebrospinal fluid cytology: Negative
measure
Complete Response Rate (CRR)
time Frame
From JCAR017 infusion until disease progression, end of study, the start of another anticancer therapy, or hemopoietic stem cell transplant (HSCT) (up to approximately 63 months)
description
Event-free survival is from JCAR017 infusion to death from any cause, progressive disease, or starting a new anticancer therapy. If a participant did not have an EFS event prior to data cutoff, EFS was censored at last disease assessment. Progressive disease (PD): * Target nodes/nodal masses: PPD progression. * Extranodal lesion: LDi \> 1.5 cm and increase by ≥ 50% from PPD nadir. * Splenomegaly: \> 50% of prior increase from baseline or by at least 2 cm from baseline. * Nonmeasured lesions: New or clear progression. * New lesions: Regrowth of previously resolved lesions. * Bone marrow: New or recurrent Progressive Disease (Cohort 5): * Brain imaging: \> 25% increase in enhancing lesion from baseline or best response. * Eye Exam: Increased vitreous cell counts or progressive retinal or optic nerve infiltration. * New lesion or site of disease
measure
Event Free Survival (EFS)
time Frame
From JCAR017 infusion to death due to any reason, progressive disease, or starting a new anticancer therapy (up to approximately 63 months).
description
Progression-free survival is defined as the interval from the date of JCAR017 infusion to progressive disease or death due to any cause, whichever occurred first. Per European Medicines Agency (EMA) criteria, participants who did not experience progressive disease and who did not die before the data cutoff date were censored at the time of the last visit with adequate response assessment when the participants were known not to have progressed. Estimated using Kaplan-Meier product-limit estimates.
measure
Progression Free Survival (PFS) Using European Medicines Agency (EMA) Criteria
time Frame
From JCAR017 infusion to progressive disease or death due to any reason, whichever occurred first (up to approximately 63 months)
description
Overall survival is defined as the interval from the date of JCAR017 infusion to the date of death due to any reason. Data from surviving participants was censored at the last time that the participant was known to be alive. Estimated using Kaplan-Meier product-limit estimates.
measure
Overall Survival (OS)
time Frame
From the date of JCAR017 infusion to the date of death due to any reason (up to approximately 63 months).
description
DOR is from first response (complete response (CR), CR unconfirmed (CRu) or partial response (PR)) to progression (PD) or death. Those without PD or death were censored at the last assessment. CR via PET-CT: Lymph/extralymph: Score 1/2/3a w/w-out resid mass, no new lesions, No FDG-avid disease in bone marrow (BM) CR via CT scan: Lymph/extralymph: Target/nodal ≤ 1.5 cm, no new lesions, normal BM CR Cohort 5: No contrast enhance, no corticosteroid, normal eye exam, neg CSF cytology CRu Cohort 5: No contrast enhance, min abnorm, normal eye exam, neg CSF cytology PR via PET-CT: Lymph/extralymph: Score 4/5b, red uptake, no new lesions, resid uptake incr, reduced in BM PR via CT scan: Lymph/extralymph: 50% decr in sum of diam ≤ 6 target/extranodal, no new/nonmeasured lesions, Organ enlarge: Spleen decr \> 50% PR Cohort 5: 50% decr in enhancing tumor, no contrast enhance, Eye exam: Minor abnorm, decr in vitreous cells/retinal infiltrate, negative, persist or suspic CSF cytology.
measure
Duration of Response (DOR)
time Frame
From JCAR017 infusion until disease progression, death due to any reason, end of study, the start of another anticancer therapy, or hemopoietic stem cell transplant (HSCT) (up to approximately 63 months)
description
Cmax is the maximum or peak concentration of drug reached in the plasma following a dose of the drug. Quantitative polymerase chain reaction (qPCR) was used to determine Cmax by detecting the JCAR017 transgene. Baseline is defined as the last available recorded value on or prior to the date of JCAR017 infusion.
measure
Maximum Concentration (Cmax) of JCAR017 by qPCR
time Frame
At baseline and up until 24 months post JCAR017 infusion
description
Time to maximum concentration (Tmax) is the time it takes for a drug to reach the maximum concentration (Cmax) after administration. Quantitative polymerase chain reaction (qPCR) was used to determine Tmax by detecting the JCAR017 transgene. Baseline is defined as the last available recorded value on or prior to the date of JCAR017 infusion.
measure
Time to Peak Concentration (Tmax) of JCAR017 by qPCR
time Frame
At baseline and up until 24 months post JCAR017 infusion

Full study description

brief Summary: The purpose of this study is to evaluate the efficacy and safety of JCAR017 in participants with aggressive B-cell non-Hodgkin lymphoma (B-NHL)
detailed Description: This is a study to determine the efficacy and safety of JCAR017 in adult participants with aggressive B-cell NHL. The study will enroll participants in Europe and Japan with diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS; de novo or transformed follicular lymphoma \[tFL\]), high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (HGBL), follicular lymphoma Grade 3B (FL3B), and primary central nervous system lymphoma (PCNSL). Participants with secondary central nervous system (CNS) involvement are allowed. Once enrolled, participants will undergo leukapheresis to enable JCAR017 cell product generation. Upon successful JCAR017 cell product generation, participants will receive lymphodepleting chemotherapy followed by infusion of JCAR017. JCAR017 will be administered by intravenous infusion. Participants will be followed for approximately 2 years after their JCAR017 infusion for safety, disease status, survival and health-related quality of life. Delayed adverse events following exposure to gene modified T cells will be assessed and long-term persistence of these modified T cells will continue to be monitored under a separate long-term follow-up protocol for up to 15 years after JCAR017 infusion as per competent authority guidelines.

Source references

references

citation
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.
pmid
34515338
type
DERIVED