Clinical trial NCT03744676: A Safety Trial of Lisocabtagene Maraleucel (JCAR017) for Relapsed and Refractory (R/R) B-cell Non-Hodgkin Lymphoma (NHL) in the Outpatient Setting (TRANSCEND-OUTREACH-007)
Official title: A Safety Trial of Lisocabtagene Maraleucel (JCAR017) for Relapsed and Refractory (R/R) B-cell Non-Hodgkin Lymphoma (NHL) in the Outpatient Setting
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
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
Lead sponsor: Juno Therapeutics, a Subsidiary of Celgene
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2018-11-16
Enrollment: 104
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 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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With Cytokine Release Syndrome (CRS) Adverse Events Grade ≥ 3
timeFrame: From first dose to 90 days following first dose (up to approximately 90 days)
measure: Percentage of Participants With Neurotoxicity (NT) Adverse Events Grade ≥ 3
timeFrame: From first dose to 90 days following first dose (up to approximately 90 days)
measure: Percentage of Participants With Infection Adverse Events Grade ≥ 3
timeFrame: From first dose to 90 days following first dose (up to approximately 90 days)
measure: Percentage of Participants With Grade ≥ 3 Prolonged Cytopenia at Day 29.
timeFrame: At Day 29 after first treatment
Secondary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: From first dose to 90 days following first dose (up to approximately 90 days)
measure: Number of Participants With Clinically Significant Laboratory Abnormalities- Hematology
timeFrame: From first dose to up to 41 months
measure: Number of Participants With Clinically Significant Laboratory Abnormalities- Chemistry
timeFrame: From first dose to up to 41 months
measure: Number of Participants With Adverse Events Grade ≥ 3
timeFrame: From first dose to 90 days following first dose (up to approximately 90 days)
measure: Time to Onset and Time to Resolution of Grade ≥ 3 Cytokine Release Syndrome (CRS)
timeFrame: From first dose to up to approximately 41 months
measure: Time to Onset and Time to Resolution of Grade ≥ 3 Neurotoxicity (NT)
timeFrame: From first dose to up to approximately 41 months
measure: Number of Participants Administered Tocilizumab and Corticosteroid for Management of Cytokine Release Syndrome (CRS)
timeFrame: From first dose to up to approximately 41 months
measure: Number of Participants Administered Tocilizumab and Corticosteroid for Management of Neurotoxicity (NT)
timeFrame: From first dose to up to study completion (Approximately 57 Months and 24 days)
measure: Objective Response Rate (ORR)
timeFrame: From first dose to up to approximately 41 months
measure: Complete Response Rate (CRR)
timeFrame: From first dose to up to approximately 41 months
measure: Duration of Response (DoR) and Duration of Complete Response (DoCR)
timeFrame: From first dose to up to approximately 41 months
measure: Progression Free Survival (PFS)
timeFrame: From first dose to up to study completion (Approximately 57 Months and 24 days)
measure: Overall Survival (OS)
timeFrame: From first dose to up to study completion (Approximately 57 Months and 24 days)
measure: Area Under the Blood Concentration-time Curve From Time to Zero to 28 Days After Dosing AUC (0-28)
timeFrame: 28days after first dose
measure: Maximum Observed Blood Concentration (Cmax)
timeFrame: 28days after first dose
measure: Time of Maximum Observed Blood Concentration (Tmax)
timeFrame: 28days after first dose
measure: Mean Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30
timeFrame: From Enrollment to end of follow up, approximately 26 months
measure: Mean Change From Baseline in EuroQol Instrument EQ-5D-5L.
timeFrame: Post Dose Month 24
measure: Number of Intensive Care Unit (ICU) Inpatient Days and Non-ICU Inpatient Days and Reasons for Hospitalization
timeFrame: From first hospitalization to the last. Approximately 31 days
measure: Number of Participants Who Received Transfusions
timeFrame: From first dose to end of treatment period approximately 24 months
measure: Number of Participants Requiring Growth Factor Support.
timeFrame: From first dose to end of treatment period approximately 24 months
measure: Number of Participants Requiring Intravenous Immunoglobulin (IVIG) Support
timeFrame: From first dose to end of treatment period approximately 24 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Local Institution - 0057
state: California
city: Denver
country: United States
facility: Local Institution - 0060
state: Colorado
city: Miami
country: United States
facility: Local Institution - 0089
state: Florida
city: Orlando
country: United States
facility: Local Institution - 0081
state: Florida
city: Indianapolis
country: United States
facility: Local Institution - 0065
state: Indiana
city: Wichita
country: United States
facility: Local Institution - 0069
state: Kansas
city: Louisville
country: United States
facility: Local Institution - 0064
state: Kentucky
city: Southfield
country: United States
facility: Local Institution - 0101
state: Michigan
city: East Brunswick
country: United States
facility: Local Institution - 0052
state: New Jersey
city: Morristown
country: United States
facility: Local Institution - 0066
state: New Jersey
city: Albany
country: United States
facility: Local Institution - 0041
state: New York
city: Cincinnati
country: United States
facility: Local Institution - 0039
state: Ohio
city: Eugene
country: United States
facility: Local Institution - 0098
state: Oregon
city: Portland
country: United States
facility: Local Institution - 0051
state: Oregon
city: Lancaster
country: United States
facility: Lancaster General Hospital
state: Pennsylvania
city: Greenville
country: United States
facility: Local Institution - 0037
state: South Carolina
city: Nashville
country: United States
facility: Local Institution - 0063
state: Tennessee
city: Dallas
country: United States
facility: Local Institution - 0097
state: Texas
city: San Antonio
country: United States
facility: Local Institution - 0061
state: Texas
city: Temple
country: United States
facility: Baylor Scott and White Health
state: Texas
city: Tyler
country: United States
facility: Local Institution - 0096
state: Texas
city: Salt Lake City
country: United States
facility: Local Institution - 0074
state: Utah
city: Norfolk
country: United States
facility: Local Institution - 0036
state: Virginia
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
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.