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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)

Primary Purpose

Lymphoma, Non-Hodgkin, Lymphoma, Lymphoma, B-Cell

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
lisocabtagene maraleucel
Sponsored by
Juno Therapeutics, a Subsidiary of Celgene
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma, Non-Hodgkin focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age β‰₯ 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

Sites / Locations

  • Local Institution - 0057
  • Local Institution - 0060
  • Local Institution - 0089
  • Local Institution - 0081
  • Local Institution - 0065
  • Local Institution - 0069
  • Local Institution - 0064
  • Local Institution - 0101
  • Local Institution - 0052
  • Local Institution - 0066
  • Local Institution - 0041
  • Local Institution - 0039
  • Local Institution - 0098
  • Local Institution - 0051
  • Lancaster General Hospital
  • Local Institution - 0037
  • Local Institution - 0063
  • Local Institution - 0097
  • Local Institution - 0061
  • Baylor Scott and White Health
  • Local Institution - 0096
  • Local Institution - 0074
  • Local Institution - 0036

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Lisocabtagene maraleucel

Arm Description

Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of lisocabtagene maraleucel. During lisocabtagene maraleucel production, subjects may receive low-dose chemotherapy for disease control. Upon successful generation of lisocabtagene maraleucel product, subjects will receive treatment which will include lymphodepleting chemotherapy followed by one dose of lisocabtagene maraleucel administered by intravenous (IV) injection.

Outcomes

Primary Outcome Measures

Adverse events
Proportion of subjects experiencing cytokine release syndrome, neurotoxicity, prolonged cytopenias, infections AE of Grade 3 or higher

Secondary Outcome Measures

Adverse events
Proportion of subjects experiencing all AEs and laboratory abnormalities
Adverse events
Median time to onset and to resolution of cytokine release syndrome and neurotoxicity of Grade 3 or higher
Adverse Events
Management of cytokine release syndrome and neurotoxicity
Adverse Events
Of subjects monitored in the outpatient setting, the proportion of subjects experiencing all AEs and laboratory abnormalities
Objective response rate (ORR)
Objective response rate (ORR [complete response + partial response]) according to the Lugano Classification
Complete response (CR) rate
Complete response rate according to the Lugano Classification
Duration of response (DOR) and duration of complete response (DoCR)
Each defined as time from first response to progressive disease (PD) or death
Progression-free Survival (PFS)
Time from infusion of lisocabtagene maraleucel to PD or death, whichever is earlier
Overall Survival (OS)
Defined as the time from infusion of lisocabtagene maraleucel to the date of death
Pharmacokinetics- Maximum concentration (Cmax)
Maximum concentration of lisocabtagene maraleucel
Pharmacokinetics- Time of the maximum concentration (Tmax)
Time to peak concentration of lisocabtagene maraleucel in the blood
Pharmacokinetics- area under the curve
Area under the curve of lisocabtagene maraleucel in blood
Health-related quality of life questionnaires
The European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 is a validated quality of life measure applicable to subjects with any cancer diagnosis. It is composed of 30 items that address general physical symptoms, physical functioning, fatigue and malaise, and social and emotional functioning. Subscale scores are transformed to a 0 to 100 scale, with higher scores on functional scales indicating better function and higher scores on symptom scales indicating worse symptoms.
Health-related quality of life questionnaires
The EuroQol-5D (EQ-5D) is a standardized measure of health status developed by the EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal. The EQ-5D-5L consists of the EQ-5D-5L descriptive system and the EQ Visual Analogue scale (EQ VAS). The descriptive system comprises dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). Each dimension has 5 levels (no problems, slight problems, moderate problems, severe problems, extreme problems). The VAS rating scale is a vertical 20 cm visual analogue scale with the end points labeled best imaginable health state at the top and worst imaginable health state at the bottom having numeric values of 100 and 0 respectively. The participant is asked to indicate his/her health state by ticking (or placing a cross) in the box against the most appropriate statement in each of the 5 dimensions.
Health economics and outcomes research
For subjects hospitalized post-treatement, the number of days the subjects were hospitalized, including the number of days that the subjects were in the Intensive Care Unit (ICU) and non-ICU ward
Health economics and outcomes research
The percentage of lisocabtagene maraleucel-treated subjects hospitalized post-treatment for each reason will be reported.

Full Information

First Posted
November 7, 2018
Last Updated
October 5, 2023
Sponsor
Juno Therapeutics, a Subsidiary of Celgene
Collaborators
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT03744676
Brief Title
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

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 29, 2018 (Actual)
Primary Completion Date
October 16, 2023 (Anticipated)
Study Completion Date
October 16, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Juno Therapeutics, a Subsidiary of Celgene
Collaborators
Bristol-Myers Squibb

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
41 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lisocabtagene maraleucel
Arm Type
Experimental
Arm Description
Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of lisocabtagene maraleucel. During lisocabtagene maraleucel production, subjects may receive low-dose chemotherapy for disease control. Upon successful generation of lisocabtagene maraleucel product, subjects will receive treatment which will include lymphodepleting chemotherapy followed by one dose of lisocabtagene maraleucel administered by intravenous (IV) injection.
Intervention Type
Biological
Intervention Name(s)
lisocabtagene maraleucel
Other Intervention Name(s)
JCAR017, liso-cel
Intervention Description
lisocabtagene maraleucel will be administered as single dose intravenous (IV) injection
Primary Outcome Measure Information:
Title
Adverse events
Description
Proportion of subjects experiencing cytokine release syndrome, neurotoxicity, prolonged cytopenias, infections AE of Grade 3 or higher
Time Frame
Through Month 24
Secondary Outcome Measure Information:
Title
Adverse events
Description
Proportion of subjects experiencing all AEs and laboratory abnormalities
Time Frame
Through Month 24
Title
Adverse events
Description
Median time to onset and to resolution of cytokine release syndrome and neurotoxicity of Grade 3 or higher
Time Frame
Through Month 24
Title
Adverse Events
Description
Management of cytokine release syndrome and neurotoxicity
Time Frame
Through Month 24
Title
Adverse Events
Description
Of subjects monitored in the outpatient setting, the proportion of subjects experiencing all AEs and laboratory abnormalities
Time Frame
Through Month 24
Title
Objective response rate (ORR)
Description
Objective response rate (ORR [complete response + partial response]) according to the Lugano Classification
Time Frame
Through Month 24
Title
Complete response (CR) rate
Description
Complete response rate according to the Lugano Classification
Time Frame
Through Month 24
Title
Duration of response (DOR) and duration of complete response (DoCR)
Description
Each defined as time from first response to progressive disease (PD) or death
Time Frame
Through Month 24
Title
Progression-free Survival (PFS)
Description
Time from infusion of lisocabtagene maraleucel to PD or death, whichever is earlier
Time Frame
Through Month 24
Title
Overall Survival (OS)
Description
Defined as the time from infusion of lisocabtagene maraleucel to the date of death
Time Frame
Through Month 24
Title
Pharmacokinetics- Maximum concentration (Cmax)
Description
Maximum concentration of lisocabtagene maraleucel
Time Frame
Through Month 24
Title
Pharmacokinetics- Time of the maximum concentration (Tmax)
Description
Time to peak concentration of lisocabtagene maraleucel in the blood
Time Frame
Through Month 24
Title
Pharmacokinetics- area under the curve
Description
Area under the curve of lisocabtagene maraleucel in blood
Time Frame
Through Month 24
Title
Health-related quality of life questionnaires
Description
The European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 is a validated quality of life measure applicable to subjects with any cancer diagnosis. It is composed of 30 items that address general physical symptoms, physical functioning, fatigue and malaise, and social and emotional functioning. Subscale scores are transformed to a 0 to 100 scale, with higher scores on functional scales indicating better function and higher scores on symptom scales indicating worse symptoms.
Time Frame
Through Month 24
Title
Health-related quality of life questionnaires
Description
The EuroQol-5D (EQ-5D) is a standardized measure of health status developed by the EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal. The EQ-5D-5L consists of the EQ-5D-5L descriptive system and the EQ Visual Analogue scale (EQ VAS). The descriptive system comprises dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). Each dimension has 5 levels (no problems, slight problems, moderate problems, severe problems, extreme problems). The VAS rating scale is a vertical 20 cm visual analogue scale with the end points labeled best imaginable health state at the top and worst imaginable health state at the bottom having numeric values of 100 and 0 respectively. The participant is asked to indicate his/her health state by ticking (or placing a cross) in the box against the most appropriate statement in each of the 5 dimensions.
Time Frame
Through Month 24
Title
Health economics and outcomes research
Description
For subjects hospitalized post-treatement, the number of days the subjects were hospitalized, including the number of days that the subjects were in the Intensive Care Unit (ICU) and non-ICU ward
Time Frame
Through Month 24
Title
Health economics and outcomes research
Description
The percentage of lisocabtagene maraleucel-treated subjects hospitalized post-treatment for each reason will be reported.
Time Frame
Through Month 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age β‰₯ 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Local Institution - 0057
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Local Institution - 0060
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Local Institution - 0089
City
Miami
State/Province
Florida
ZIP/Postal Code
33176
Country
United States
Facility Name
Local Institution - 0081
City
Orlando
State/Province
Florida
ZIP/Postal Code
32804
Country
United States
Facility Name
Local Institution - 0065
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46237
Country
United States
Facility Name
Local Institution - 0069
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67124
Country
United States
Facility Name
Local Institution - 0064
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40207
Country
United States
Facility Name
Local Institution - 0101
City
Southfield
State/Province
Michigan
ZIP/Postal Code
48075
Country
United States
Facility Name
Local Institution - 0052
City
East Brunswick
State/Province
New Jersey
ZIP/Postal Code
08816
Country
United States
Facility Name
Local Institution - 0066
City
Morristown
State/Province
New Jersey
ZIP/Postal Code
07962
Country
United States
Facility Name
Local Institution - 0041
City
Albany
State/Province
New York
ZIP/Postal Code
12208
Country
United States
Facility Name
Local Institution - 0039
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45236
Country
United States
Facility Name
Local Institution - 0098
City
Eugene
State/Province
Oregon
ZIP/Postal Code
97401
Country
United States
Facility Name
Local Institution - 0051
City
Portland
State/Province
Oregon
ZIP/Postal Code
97213
Country
United States
Facility Name
Lancaster General Hospital
City
Lancaster
State/Province
Pennsylvania
ZIP/Postal Code
17604
Country
United States
Facility Name
Local Institution - 0037
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29615
Country
United States
Facility Name
Local Institution - 0063
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Local Institution - 0097
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
Facility Name
Local Institution - 0061
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Baylor Scott and White Health
City
Temple
State/Province
Texas
ZIP/Postal Code
76508
Country
United States
Facility Name
Local Institution - 0096
City
Tyler
State/Province
Texas
ZIP/Postal Code
75702
Country
United States
Facility Name
Local Institution - 0074
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84143
Country
United States
Facility Name
Local Institution - 0036
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23502
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Information relating to our policy on data sharing and the process for requesting data can be found at the following link: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/
IPD Sharing Time Frame
See Plan Description
IPD Sharing Access Criteria
See Plan Description
IPD Sharing URL
https://www.bms.com/researchers-and-partners/clinical-trials-and-research/disclosure-commitment.html
Citations:
PubMed Identifier
34515338
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.
Results Reference
derived
Links:
URL
https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
Description
BMS Clinical Trial Information
URL
https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm
Description
FDA Safety Alerts and Recalls
URL
https://www.bmsstudyconnect.com/s/US/English/USenHome
Description
BMS Clinical Trial Patient Recruiting

Learn more about this trial

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)

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