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)

Sponsor

Juno Therapeutics, a Subsidiary of Celgene (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03744676

Collaborator

Bristol-Myers Squibb (Industry)

Enrollment

Locations

Arm

60.3

Anticipated Duration (Months)

0.9

Patients Per Site

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
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	Biological: lisocabtagene maraleucel	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

41 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Nov 29, 2018

Anticipated Primary Completion Date :

Dec 7, 2023

Anticipated Study Completion Date :

Dec 7, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lisocabtagene maraleucel 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.	Biological: lisocabtagene maraleucel lisocabtagene maraleucel will be administered as single dose intravenous (IV) injection Other Names: JCAR017 liso-cel

Arm

Intervention/Treatment

Experimental: Lisocabtagene maraleucel

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.

Biological: lisocabtagene maraleucel

lisocabtagene maraleucel will be administered as single dose intravenous (IV) injection

Other Names:

JCAR017

liso-cel

Outcome Measures

Primary Outcome Measures

Adverse events [Through Month 24]
Proportion of subjects experiencing cytokine release syndrome, neurotoxicity, prolonged cytopenias, infections AE of Grade 3 or higher

Secondary Outcome Measures

Adverse events [Through Month 24]
Proportion of subjects experiencing all AEs and laboratory abnormalities
Adverse events [Through Month 24]
Median time to onset and to resolution of cytokine release syndrome and neurotoxicity of Grade 3 or higher
Adverse Events [Through Month 24]
Management of cytokine release syndrome and neurotoxicity
Adverse Events [Through Month 24]
Of subjects monitored in the outpatient setting, the proportion of subjects experiencing all AEs and laboratory abnormalities
Objective response rate (ORR) [Through Month 24]
Objective response rate (ORR [complete response + partial response]) according to the Lugano Classification
Complete response (CR) rate [Through Month 24]
Complete response rate according to the Lugano Classification
Duration of response (DOR) and duration of complete response (DoCR) [Through Month 24]
Each defined as time from first response to progressive disease (PD) or death
Progression-free Survival (PFS) [Through Month 24]
Time from infusion of lisocabtagene maraleucel to PD or death, whichever is earlier
Overall Survival (OS) [Through Month 24]
Defined as the time from infusion of lisocabtagene maraleucel to the date of death
Pharmacokinetics- Maximum concentration (Cmax) [Through Month 24]
Maximum concentration of lisocabtagene maraleucel
Pharmacokinetics- Time of the maximum concentration (Tmax) [Through Month 24]
Time to peak concentration of lisocabtagene maraleucel in the blood
Pharmacokinetics- area under the curve [Through Month 24]
Area under the curve of lisocabtagene maraleucel in blood
Health-related quality of life questionnaires [Through Month 24]
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 [Through Month 24]
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 [Through Month 24]
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 [Through Month 24]
The percentage of lisocabtagene maraleucel-treated subjects hospitalized post-treatment for each reason will be reported.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cedars-Sinai Medical Group	Los Angeles	California	United States	90048
2	Local Institution - 0057	Los Angeles	California	United States	90048
3	Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
4	Local Institution - 0060	Denver	Colorado	United States	80218
5	Local Institution - 0089	Miami	Florida	United States	33176
6	Miami Cancer Institute at Baptist health	Miami	Florida	United States	33176
7	Advent Health Medical Group Blood & Marrow Transplant at Orlando	Orlando	Florida	United States	32804
8	Local Institution - 0081	Orlando	Florida	United States	32804
9	Indiana Blood and Marrow Transplantation	Indianapolis	Indiana	United States	46237
10	Local Institution - 0065	Indianapolis	Indiana	United States	46237
11	Local Institution - 0069	Wichita	Kansas	United States	67124
12	Cancer Center of Kansas	Wichita	Kansas	United States	67214
13	Local Institution - 0064	Louisville	Kentucky	United States	40207
14	Norton Cancer Institute	Louisville	Kentucky	United States	40207
15	Ascension Providence Hospital Southfield Cancer Center	Southfield	Michigan	United States	48075
16	Local Institution - 0101	Southfield	Michigan	United States	48075
17	Astera Cancer Care	East Brunswick	New Jersey	United States	08816
18	Local Institution - 0052	East Brunswick	New Jersey	United States	08816
19	Morristown Medical Center	Morristown	New Jersey	United States	07960
20	Local Institution - 0066	Morristown	New Jersey	United States	07962
21	Local Institution - 0041	Albany	New York	United States	12208
22	USOR - New York Oncology Hematology - Albany Cancer Center	Albany	New York	United States	12208
23	Local Institution - 0039	Cincinnati	Ohio	United States	45236
24	USOR - Oncology Hematology Care - Blue Ash	Cincinnati	Ohio	United States	45236
25	Local Institution - 0098	Eugene	Oregon	United States	97401
26	Willamette Valley Cancer Institute	Eugene	Oregon	United States	97401
27	Local Institution - 0051	Portland	Oregon	United States	97213
28	Providence Portland Medical Center	Portland	Oregon	United States	97213
29	Lancaster General Hospital	Lancaster	Pennsylvania	United States	17604
30	Local Institution - 0037	Greenville	South Carolina	United States	29615
31	Prisma Health Cancer Institute - Eastside Cancer Center	Greenville	South Carolina	United States	29615
32	Local Institution - 0063	Nashville	Tennessee	United States	37203
33	Tennessee Oncology - Nashville - Centennial	Nashville	Tennessee	United States	37203
34	Local Institution - 0097	Dallas	Texas	United States	75230
35	USOR - Texas Oncology - Medical City Dallas	Dallas	Texas	United States	75230
36	Local Institution - 0061	San Antonio	Texas	United States	78229
37	Texas Transplant Institute	San Antonio	Texas	United States	78229
38	Baylor Scott & White Medical Center - Temple	Temple	Texas	United States	76508
39	Local Institution - 0096	Tyler	Texas	United States	75702
40	USOR - Texas Oncology - Tyler	Tyler	Texas	United States	75702
41	Intermountain Healthcare - LDS Hospital Blood and Marrow Transplant	Salt Lake City	Utah	United States	84143
42	Local Institution - 0074	Salt Lake City	Utah	United States	84143
43	Local Institution - 0036	Norfolk	Virginia	United States	23502
44	USOR - Virginia Oncology Associates	Norfolk	Virginia	United States	23502