Clinical trial NCT03483103: Lisocabtagene Maraleucel (JCAR017) as Second-Line Therapy (TRANSCEND-PILOT-017006)
Official title: A Phase 2 Study of Lisocabtagene Maraleucel (JCAR017) as Second-Line Therapy in Adult Patients With Aggressive B-cell NHL (017006)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma, Non-Hodgkin
Lymphoma, Nonhodgkin
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Keywords: JCAR017
lisocabtagene maraleucel
NHL
chimeric antigen receptor
CAR
CAR T cell
autologous T cell therapy
immunotherapy
cell therapy
liso-cel
Lead sponsor: Juno Therapeutics, a Subsidiary of Celgene
Sponsor class: INDUSTRY
First posted: 2018-03-30
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Confirmation of relapsed or refractory aggressive B-cell non-Hodgkin lymphoma of the following histology at relapse: 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 (double/triple hit lymphoma \[DHL/THL\]), and follicular lymphoma Grade 3B per WHO 2016 classification
* Previous treatment must include treatment with a single line of chemoimmunotherapy containing an anthracycline and a CD20-targeted agent
* Subjects must be deemed ineligible for both high-dose chemotherapy and hematopoietic stem cell transplant (based on age, performance status and/or comorbidities) while also having adequate organ function for CAR T cell treatment.
* Positron emission tomography (PET)-positive disease
* Histological confirmation of diagnosis at last relapse. Enough tumor material must be available for central confirmation of diagnosis, otherwise a new tumor biopsy is mandated.
* ECOG performance status of 0, or 1, or 2
* Adequate vascular access for leukapheresis procedure (either peripheral line or surgically-placed line)
* Subjects must agree to use appropriate contraception
* Subjects must agree to not donate blood, organs, semen, and egg cells for usage in other individuals for at least 1 year following lymphodepleting chemotherapy

Exclusion Criteria:

* Subjects with central nervous system (CNS)-only involvement by malignancy (note: subjects with secondary CNS involvement are allowed on study)
* History of another primary malignancy that has not been in remission for at least 2 years.
* Previous treatment with CD19-targeted therapy, with the exception of prior lisocabtagene maraleucel treatment in this protocol for subjects receiving retreatment
* Active hepatitis B or hepatitis C infection at the time of screening
* History of or active human immunodeficiency virus (HIV) infection at the time of screening
* Uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate antibiotics or other treatment at the time of leukapheresis or lisocabtagene maraleucel administration
* History of any one of the following cardiovascular conditions within the past 6 months: Class III or IV heart failure as defined by the New York Heart Association, cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease
* History or presence of clinically relevant CNS pathology
* Pregnant or nursing women
* Subject does not meet protocol-specified washout periods for prior treatments
* Prior hematopoietic stem cell transplant
* 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

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: 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)
Secondary outcomes:
measure: Number of Participants With Any Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From first dose to 90 days following first dose (up to approximately 90 days)
measure: Change From Baseline of Hematology Laboratory Results: Hemoglobin
timeFrame: Baseline and Day 29
measure: Change From Baseline of Hematology Laboratory Results: Leukocytes, Lymphocytes, Neutrophils, Platelets
timeFrame: Baseline and Day 29
measure: Change From Baseline of Chemistry Laboratory Results: Albumin
timeFrame: Baseline and Day 29
measure: Change From Baseline of Chemistry Laboratory Results: Alanine Aminotransferase, Aspartate Aminotransferase, Lactate Dehydrogenase
timeFrame: Baseline and Day 29
measure: Change From Baseline of Chemistry Laboratory Results: Bilirubin, Creatinine, Direct Bilirubin, Urate
timeFrame: Baseline and Day 29
measure: Change From Baseline of Chemistry Laboratory Results: Calcium Corrected, Magnesium, Phosphate, Potassium, Sodium
timeFrame: Baseline and Day 29
measure: Complete Response (CR) Rate
timeFrame: 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)
measure: Duration of Response (DOR)
timeFrame: From first dose to up to approximately 24 months
measure: Duration of Response (DOR) in Participants With Complete Response (CR)
timeFrame: From first dose to up to approximately 24 months
measure: Progression-Free Survival (PFS)
timeFrame: From first dose to progressive disease (PD) or death (up to approximately 24 months)
measure: Event-Free Survival (EFS)
timeFrame: From first dose to death from any cause, progressive disease (PD), or starting a new anticancer therapy (up to approximately 24 months)
measure: Overall Survival (OS)
timeFrame: From first dose to date of death (up to approximately 24 months)
measure: PK Parameters of JCAR017 in Blood as Assessed by qPCR: Cmax
timeFrame: From first dose to up to 24 months
measure: PK Parameters of JCAR017 in Blood as Assessed by qPCR: Tmax
timeFrame: From first dose to up to 24 months
measure: PK Parameters of JCAR017 in Blood as Assessed by qPCR: AUC (0-28)
timeFrame: From first dose to up to 24 months
measure: Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Fatigue Subscale
timeFrame: Baseline and Day 29
measure: Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Physical Functioning Subscale
timeFrame: Baseline and Day 29
measure: Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Cognitive Functioning Subscale
timeFrame: Baseline and Day 29
measure: Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Global Health/QoL Subscale
timeFrame: Baseline and Day 29
measure: Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Role Functioning Subscale
timeFrame: Baseline and Day 29
measure: Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Emotional Functioning Subscale
timeFrame: Baseline and Day 29
measure: Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Social Functioning Subscale
timeFrame: Baseline and Day 29
measure: Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Pain Subscale
timeFrame: Baseline and Day 29
measure: Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Nausea/Vomiting Subscale
timeFrame: Baseline and Day 29
measure: Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Constipation Subscale
timeFrame: Baseline and Day 29
measure: Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Diarrhea Subscale
timeFrame: Baseline and Day 29
measure: Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Insomnia Subscale
timeFrame: Baseline and Day 29
measure: Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Dyspnea Subscale
timeFrame: Baseline and Day 29
measure: Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Appetite Loss Subscale
timeFrame: Baseline and Day 29
measure: Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Financial Difficulties Subscale
timeFrame: Baseline and Day 29
measure: Health-Related Quality of Life (HRQoL) Assessed by the FACT-Lym Subscale
timeFrame: Baseline and Day 29
measure: Health-Related Quality of Life (HRQoL) Assessed by the EuroQol Instrument EQ-5D-5L
timeFrame: Baseline and Day 29
measure: Numbers of Intensive Care Unit (ICU) Inpatient Days
timeFrame: From first dose after JCAR017 infusion to up to approximately 24 months
measure: Numbers of Non-intensive Care Unit (ICU) Inpatient Days
timeFrame: From first dose after JCAR017 infusion to up to approximately 24 months
measure: The Number of Participants That Were Hospitalized For Adverse Events, Prophylaxis, Other
timeFrame: From first dose after JCAR017 infusion to up to approximately 24 months
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Gilbert
country: United States
facility: Local Institution - 0043
state: Arizona
city: La Jolla
country: United States
facility: Scripps Clinic
state: California
city: Los Angeles
country: United States
facility: UNC School of Medicine
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: Sacramento
country: United States
facility: Sutter Hematology and Oncology
state: California
city: Sacramento
country: United States
facility: Sutter Medical Center
state: California
city: Stanford
country: United States
facility: Stanford Cancer Genetics Clinic
state: California
city: Stanford
country: United States
facility: Local Institution - 0092
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Atlanta
country: United States
facility: Local Institution - 0019
state: Georgia
city: Atlanta
country: United States
facility: The Blood and Marrow Transplant Group of Georgia
state: Georgia
city: Atlanta
country: United States
facility: UNC School of Medicine
state: Georgia
city: Chicago
country: United States
facility: Local Institution - 0003
state: Illinois
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Local Institution - 0016
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Lexington
country: United States
facility: Local Institution - 0046
state: Kentucky
city: Lexington
country: United States
facility: University of Kentucky/Markey Cancer Center
state: Kentucky
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Louisville
country: United States
facility: Local Institution - 0064
state: Kentucky
city: Louisville
country: United States
facility: Norton Cancer Institute - Brownsboro
state: Kentucky
city: Louisville
country: United States
facility: UNC School of Medicine
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Oncology Center Bunting Blaustein Building
state: Maryland
city: Baltimore
country: United States
facility: Local Institution - 0009
state: Maryland
city: Baltimore
country: United States
facility: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: East Brunswick
country: United States
facility: Local Institution - 0052
state: New Jersey
city: East Brunswick
country: United States
facility: Regional Cancer Care Associates
state: New Jersey
city: East Brunswick
country: United States
facility: UNC School of Medicine
state: New Jersey
city: Albany
country: United States
facility: New York Oncology Hematology - Albany Cancer Center
state: New York
city: Albany
country: United States
facility: New York Oncology Hematology P.C.
state: New York
city: Rochester
country: United States
facility: Local Institution - 0090
state: New York
city: Rochester
country: United States
facility: University of Rochester Cancer Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Charlotte
country: United States
facility: Local Institution - 0021
state: North Carolina
city: Cincinnati
country: United States
facility: Local Institution - 0039
state: Ohio
city: Cincinnati
country: United States
facility: Oncology Hematology Care, Inc.
state: Ohio
city: Cincinnati
country: United States
facility: Oncology Hematology Care
state: Ohio
city: Portland
country: United States
facility: Local Institution - 0051
state: Oregon
city: Portland
country: United States
facility: Providence Cancer Center/Earle A. Chiles Res. Inst.
state: Oregon
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Pittsburgh
country: United States
facility: Local Institution - 0029
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center Hillman Cancer Center
state: Pennsylvania
city: Greenville
country: United States
facility: Greenville Health System - Cancer Institute - Faris Road
state: South Carolina
city: Greenville
country: United States
facility: Greenville Health System
state: South Carolina
city: Greenville
country: United States
facility: Local Institution - 0037
state: South Carolina
city: Dallas
country: United States
facility: Local Institution - 0083
state: Texas
city: Dallas
country: United States
facility: UNC School of Medicine
state: Texas
city: Salt Lake City
country: United States
facility: Intermountain Healthcare - LDS Hospital Blood and Marrow Transplant
state: Utah
city: Salt Lake City
country: United States
facility: Intermountain Healthcare - LDS Hospital
state: Utah
city: Salt Lake City
country: United States
facility: Local Institution - 0074
state: Utah
city: Tacoma
country: United States
facility: Northwest Medical Specialties
state: Washington
city: Tacoma
country: United States
facility: UNC School of Medicine
state: Washington
city: Milwaukee
country: United States
facility: Local Institution - 0055
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin, Froedtert Hospital
state: Wisconsin
city: Milwaukee
country: United States
facility: UNC School of Medicine
state: Wisconsin
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Sehgal A, Hoda D, Riedell PA, Ghosh N, Hamadani M, Hildebrandt GC, Godwin JE, Reagan PM, Wagner-Johnston N, Essell J, Nath R, Solomon SR, Champion R, Licitra E, Fanning S, Gupta N, Dubowy R, D'Andrea A, Wang L, Ogasawara K, Thorpe J, Gordon LI. Lisocabtagene maraleucel as second-line therapy in adults with relapsed or refractory large B-cell lymphoma who were not intended for haematopoietic stem cell transplantation (PILOT): an open-label, phase 2 study. Lancet Oncol. 2022 Aug;23(8):1066-1077. doi: 10.1016/S1470-2045(22)00339-4. Epub 2022 Jul 12.
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.