Plain English Summary
Background and study aims
B-cell non-Hodgkin lymphoma (NHL) is a cancer that starts in specific type of white blood cells 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-90009530, 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-90009530 can be used in future studies for the treatment of B-cell Non-Hodgkin Lymphoma 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. Men and women 18 years or older with B-cell NHL who have relapsed or refractory disease after 2 prior treatments will be enrolled.
Who can participate?
Patients aged 18 years or older with relapsed or refractory disease for each histologic subtype-Mature aggressive large B cell NHL and Follicular Lymphoma Grade 3b.
What does the study involve?
This study will be conducted in 2 parts which consists of run in and dose expansion.
Run In: The participants will undergo lymphodepletion and then receive JNJ-90009530 through intravenous infusion on Day 1.
Expansion: Participants will receive JNJ- 90009530 infusion at the recommended phase 2 dose(s) confirmed after the Run In.
What are the possible benefits and risks of participating?
Benefits:
This is the first study using the study drug JNJ-90009530. 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-90009530 in relapsed/refractory B cell Non-Hodgkin Lymphoma
Risks:
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’ body will also be done to monitor disease status. The possible side effects of the study drug will be recorded during the study. Blood samples will be taken at multiple timepoints to understand how the body responds to study drug. The total duration of study is approximately 2 years and 7 months.
Not all possible side effects and risks related to JNJ-90009530 are known, since this is the first time JNJ-90009530 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.
To minimise the risks associated with this, participants are frequently reviewed after receiving JNJ-90009530 for side effects and adverse events. Additionally, safety assessments will be obtained during the Post-Infusion Follow-up and Post Treatment phases.
Participants are educated to report any symptoms and side effects to the study staff without delay. Any serious adverse events that are reported to the Sponsor are thoroughly reviewed by a specialist drug safety team. The Participant Information Sheet/Informed Consent Form (PIS/ICF), which will be signed by every participant agreeing to participate in the study, includes a detailed section outlining potential risks/side effects to participating in the study. Please see the attached PIS/ICF copy included in this submission.
Immunological effects
• Cytokine release syndrome (CRS)
• Immune Effector Cell-associated HLH-like Syndrome (IEC-HS)
• Immune effector cell associated neurotoxicity syndrome (ICANS)
Other possible side effects
• Blood cell effects
• Risk of infections
• Hypogammaglobulinemia
• Tumor Lysis Syndrome
• Allergic Reactions
• Pneumonitis
Where is the study run from?
When is the study starting and how long is it expected to run for?
Who is funding the study?
Who is the main contact?
Aakta Al-Naqdi, aalnaqdi@its.jnj.com (Public)
maeve.o'reilly@nhs.net (Principal Investigator)
medinfo@its.jnj.com (Scientific)
Study website
Contact information
Type
Public
Contact name
Dr Aakta Al-Naqdi
ORCID ID
Contact details
50-100 Holmers Farm Way
High Wycombe
HP12 4DP
United Kingdom
+44 (0) 7880443442
aalnaqdi@its.jnj.com
Type
Principal Investigator
Contact name
Dr Maeve O'Reilly
ORCID ID
Contact details
250 Euston Road
London
NW1 2PG
United Kingdom
+44 (203) 456 7890
maeve.o'reilly@nhs.net
Type
Scientific
Contact name
Dr Medical Information and Product Information Enquiry .
ORCID ID
Contact details
50-100 Holmers Farm Way
High Wycombe
HP12 4DP
United Kingdom
+44 (0)800 731 8450
medinfo@its.jnj.com
Additional identifiers
EudraCT/CTIS number
2023-506259-97
IRAS number
1009316
ClinicalTrials.gov number
NCT05784441
Protocol/serial number
90009530LYM1001, IRAS 1009316, CPMS 57721
Study information
Scientific title
A Phase 1b Multicenter, Open-label, Study of JNJ-90009530, an Autologous Anti-CD20 CAR-T Cell Therapy in Adult Participants with Relapsed or Refractory B-cell Non- Hodgkin Lymphoma
Acronym
Study hypothesis
Primary objectives:
1. To check if JNJ-90009530 is safe and well-tolerated.
2. To find the most effective dose (Recommended Phase 2 Dose [s]) of JNJ-90009530.
Secondary objectives:
1. To examine JNJ-90009530 in participants with relapsed (reoccurrence) B-cell non-Hodgkin lymphoma cancer 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).
2. To examine how JNJ-90009530 is absorbed, processed, and eliminated by the body (pharmacokinetics).
Ethics approval(s)
Approved 22/02/2024, London - West London & GTAC Research Ethics Committee (2 Redman Place, London, E20 1JQ, United Kingdom; +44 (0)207 104 8241; westlondon.rec@hra.nhs.uk), ref: 24/LO/0010
Study design
Interventional non randomized
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 study, 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 prior to apheresis
• Apheresis/Enrollment
• Bridging therapy: For participants who are at high risk to experience disease progression during the manufacture of JNJ-90009530 drug product and before lymphodepletion, a bridging therapy is allowed at the investigator’s discretion and Sponsor’s approval.
• Lymphodepletion: Day -5 to Day -3 (window to begin lymphodepletion: Day -7 to Day -5)
• JNJ-90009530 single infusion: Day 1
• Post-infusion follow-up: Beginning after JNJ-90009530 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 postinfusion
• 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-90009530
Primary outcome measure
1. 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-90009530 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-90009530 in blood over time for up to 24 months
Overall study start date
05/01/2024
Overall study end date
01/04/2027
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
17/05/2024
Recruitment end date
31/03/2025
Locations
Countries of recruitment
Australia, Belgium, Denmark, France, Germany, Israel, Spain, United Kingdom
Study participating centre
University College London Hospitals NHS Foundation Trust
250 Euston Road
London
NW1 2PG
United Kingdom
Sponsor information
Organisation
Janssen-Cilag International NV
Sponsor details
Archimedesweg 29
Leiden
2333 CM
Netherlands
-
ClinicalTrialsEU@its.jnj.com
Sponsor type
Industry
Website
Funders
Funder type
Industry
Funder name
Janssen Research & Development, LLC
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
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
01/04/2028
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, Data sharing statement to be made available at a later date
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|