Plain English Summary
Background and study aims
B-cell non-Hodgkin lymphoma (NHL) is a cancer that starts in a specific type of white blood cell called B lymphocytes. The symptoms include lymph nodes (part of the body’s immune system) that are larger than normal, fever, and weight loss. Although treatments are available, it can come back after treatment (relapse) or can be resistant to standard treatment (refractory). There is a need for the continued development of safe and effective treatments. The study treatment, JNJ-90014496, is made by using a type of white blood cells (T-cells) from the participant. These cells are changed in the laboratory so that they attack cancer cells when they are put back into the participant’s blood. The purpose of this study is to see if JNJ-90014496 can be used in future studies for the treatment of B-cell NHL in adults. During the study, side effects caused by the study drug will be followed closely, as well as how long the study drug stays in the body and how the body responds to it.
Who can participate?
Men and women 18 years or older with B-cell NHL who have relapsed or refractory disease after 2 prior treatments will be enrolled.
What does the study involve?
This study will be conducted in 2 parts which consist of run-in and dose expansion phases.
Run In: The participants will undergo lymphodepletion and then receive JNJ-90014496 through intravenous infusion on Day 1.
Expansion: Participants will receive JNJ-90014496 infusion at the recommended phase 2 dose(s) confirmed after the Run In.
Participants will be monitored for their long-term follow-up period after the post-treatment follow-up. Participants will undergo study assessments and tests, such as blood tests, and vital signs. Scans of the participants’ bodies will also be done to monitor disease status.
What are the possible benefits and risks of participating?
This is the first study using the study drug JNJ-90014496. As such, the benefits associated with this treatment are unknown. Taking part in this study may improve the participant’s condition but these benefits are not guaranteed to happen, and there may not be any clinical benefit to being in this study. Participation may help future patients as researchers understand more about the possible effectiveness and safety of JNJ-90014496 in relapsed/refractory B cell non-Hodgkin lymphoma.
The possible side effects of the study drug will be recorded during the study. Blood samples will be taken at multiple time points to understand how the body responds to the study drug. The total duration of the study is approximately 2 years and 7 months.
Not all possible side effects and risks related to JNJ-90014496 are known since this is the first time JNJ-90014496 has been given to humans. Different or unexpected side effects may occur. Side effects may go away after treatment is stopped, but they may be serious, long-lasting, or permanent and may even result in hospitalisation or death.
Where is the study run from?
Janssen-Cilag International NV
When is the study starting and how long is it expected to run for?
January 2024 to October 2027
Who is funding the study?
Janssen Research and Development
Who is the main contact?
Principal Investigator Maeve O'Reilly, maeve.o'reilly@nhs.net
Study website
Contact information
Type
Principal Investigator
Contact name
Dr Maeve O'Reilly
ORCID ID
Contact details
University College London Hospital
250 Euston Road
London
NW1 2PG
United Kingdom
+44 (0)203 456 7890
maeve.o'reilly@nhs.net
Type
Scientific
Contact name
Dr Medical Information and Product Information Enquiry
ORCID ID
Contact details
-
-
-
United Kingdom
+44 (0)800 731 8450, (0)1494 567444
medinfo@its.jnj.com
Type
Public
Contact name
Dr Aakta Al-Naqdi
ORCID ID
Contact details
Senior Local Trial Manager
ED&CP
Janssen UK
50-100 Holmers Farm Way
High Wycombe
Buckinghamshire
HP12 4DP
United Kingdom
+44 (0) 7880443442
aalnaqdi@its.jnj.com
Additional identifiers
EudraCT/CTIS number
2023-506267-33
IRAS number
1008775
ClinicalTrials.gov number
NCT05421663
Protocol/serial number
90014496LYM1001, IRAS 1008775, CPMS 58328
Study information
Scientific title
A phase Ib multicenter, open-label, study of JNJ-90014496, an autologous CD19/CD20 Bi-specific CAR-T cell therapy in adult participants with relapsed or refractory B-cell non-Hodgkin lymphoma
Acronym
Study hypothesis
• To check if JNJ-90014496 is safe and well-tolerated.
• To find the most effective dose (recommended phase 2 dose [RP2D]) of JNJ-90014496.
• To examine JNJ-90014496 in participants with B-cell non-Hodgkin lymphoma cancer that is relapsed (reoccurrence) after or resistant to standard therapies, to check how many people respond well overall (overall response rate), how quickly they respond (time to response) and how long the positive response lasts (duration of response).
• To examine how JNJ-90014496 is absorbed, processed, and eliminated by the body (pharmacokinetic) over time.
Ethics approval(s)
Approved 01/03/2024, North East - York Research Ethics Committee (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 (0)207 104 8079; york.rec@hra.nhs.uk), ref: 24/NE/0006
Study design
Phase Ib multicenter open-label study
Primary study design
Interventional
Secondary study design
Non randomised study
Study setting(s)
Hospital
Study type
Safety, Efficacy
Patient information sheet
Condition
Non-Hodgkin lymphoid malignancies
Intervention
This is an open-label, single-drug administration study.
Up to 12 adult participants with r/r aggressive B-cell NHL may be enrolled into a Run-In dose level.
After completion of the Run-In, an aggressive lymphoma and an indolent lymphoma Dose Expansion cohort may open. Up to approx. 40 participants may be enrolled in each Dose Expansion cohort, allowing for up to approx. 92 participants to be enrolled in total.
For both the Run-In and Dose Expansion, the study periods and durations for participants are:
• Screening: <28 days before apheresis
• Apheresis/Enrollment
• Bridging therapy: For participants at high risk of experiencing disease progression during the manufacture of the JNJ-90014496 drug product and before lymphodepletion, a bridging therapy is allowed at the investigator’s discretion and the Sponsor’s approval.
• Lymphodepletion: Day -5 to Day -3 (window to begin lymphodepletion: Day -7 to Day -5)
• JNJ-90014496 single infusion: Day 1
• Post-infusion follow-up: Beginning after JNJ-90014496 infusion (DLT period: Days 1 to 29) and continuing up to Day 90
• Post-treatment follow-up: Beginning after post-infusion follow-up and continuing 2 years post-infusion
• Long-term follow-up: beginning after post-treatment follow-up
Intervention type
Drug
Pharmaceutical study type(s)
Pharmacokinetic, Pharmacodynamic, Dose response, Therapy
Phase
Phase I
Drug/device/biological/vaccine name(s)
JNJ-90014496
Primary outcome measure
Occurrence of AEs and abnormal laboratory results, including dose limiting toxicities (DLTs) for up to 24 months
Secondary outcome measures
1. Overall Response (OR), which includes Partial Response (PR) and Complete Response (CR), for up to 24 months
2. Time to response (TTR), defined as the time from the date of JNJ-90014496 infusion to the first documented CR or PR for up to 24 months
3. Duration of response (DOR), defined as the time from the first documented CR or PR to relapse or death (whichever occurs first) for up to 24 months
4. Amount of JNJ-90014496 in blood over time for up to 24 months
Overall study start date
17/01/2024
Overall study end date
28/10/2027
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Participant must be greater than or equal to (>=) 18 years of age, at the time of signing informed consent
2. All participants must have relapsed or refractory disease for each histologic subtype - Mature aggressive large B cell NHL and Follicular Lymphoma Grade 3b: Participants must have >= 2 lines of systemic therapy or >=1 line of systemic therapy in case of participants ineligible for high-dose chemotherapy and autologous Hematopoietic stem cell transplantation (HSCT). Participants also must have had exposure to an anthracycline and an anti-CD20 targeted agent-Follicular lymphoma Grade 1-3a and Marginal Zone Lymphoma: Participants must have >=2 prior lines of anti-neoplastic systemic therapy. Participants also must have prior exposure to an anti-CD20 monoclonal antibody
3. Tumor must be cluster of differentiation (CD) 20 positive
4. Measurable disease as defined by Lugano 2014 classification
5. Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1
Participant type(s)
Patient
Age group
Adult
Lower age limit
18 Years
Sex
Both
Target number of participants
92
Participant exclusion criteria
1. Diagnosis of Human herpes virus (HHV) 8-positive Diffuse large B Cell lymphoma (DLBCL)
2. Prior allogeneic Hematopoietic stem cell transplantation (HSCT)
3. Autologous stem cell transplant within 12 weeks of chimeric antigen receptor (CAR) T cell infusion
4. Uncontrolled active infections
5. History of deep vein thrombosis or pulmonary embolism within six months of infusion (except for line associated deep vein thrombosis [DVT])
6. History of stroke, unstable angina, myocardial infarction, congestive heart failure ( New York Heart Association [NYHA] Class III or IV), severe cardiomyopathy or ventricular arrhythmia requiring medication or mechanical control within 6 months of screening
7. History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease or neurodegenerative disorder
8. Known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system
9. Active central nervous system (CNS) involvement by malignancy
10. Current active liver or biliary disease (except for Gilbert’s syndrome or asymptomatic gallstones)
Recruitment start date
25/04/2024
Recruitment end date
01/09/2025
Locations
Countries of recruitment
Australia, Canada, Denmark, France, Germany, Netherlands, Spain, United Kingdom
Study participating centre
University College London Hospitals NHS Foundation Trust
250 Euston Road
London
NW1 2PG
United Kingdom
Study participating centre
The Christie NHS Foundation Trust
550 Wilmslow Road
Withington
Manchester
M20 4BX
United Kingdom
Sponsor information
Organisation
Janssen-Cilag International NV
Sponsor details
Archimedesweg 29
Leiden
2333 CM
Netherlands
None provided
ClinicalTrialsEU@its.jnj.com
Sponsor type
Industry
Website
Funders
Funder type
Industry
Funder name
Janssen Research and Development
Alternative name(s)
Janssen R&D, Janssen Research & Development, Janssen Research & Development, LLC, Janssen Research & Development LLC, JRD, J&J PRD
Funding Body Type
private sector organisation
Funding Body Subtype
For-profit companies (industry)
Location
United States of America
Results and Publications
Publication and dissemination plan
Peer reviewed scientific journals
Internal report
Conference presentation
Submission to regulatory authorities
Results of the study will be available to the wider scientific community via publication in scientific journals and presentation at scientific meetings. Study results summary will also be published in the ISRCTN Registry and may be available on the HRA website's Research Summaries page.
Intention to publish date
28/10/2028
Individual participant data (IPD) sharing plan
The datasets generated during and/or analysed during the current study are not expected to be made available due to commercial confidentiality.
IPD sharing plan summary
Not expected to be made available
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|