A study of JNJ-89853413 for relapsed or refractory acute myeloid leukemia or myelodysplastic neoplasms
| ISRCTN | ISRCTN16221474 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN16221474 |
| ClinicalTrials.gov (NCT) | NCT06618001 |
| Clinical Trials Information System (CTIS) | 2024-513199-16 |
| Integrated Research Application System (IRAS) | 1010815 |
| Protocol serial number | 89853413AML1001, CPMS 64352 |
| Sponsor | Janssen (Netherlands) |
| Funder | Janssen Research and Development |
- Submission date
- 11/10/2024
- Registration date
- 04/12/2024
- Last edited
- 11/02/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Plain English summary of protocol
Background and study aims
Acute leukemias are characterized by uncontrolled proliferation of immature white blood cells (WBCs) in bone marrow (soft, fatty tissue inside of bone cavities), peripheral blood and/or other sites in the body. Acute myeloid leukemia (AML) and myelodysplastic neoplasms (MDS) are cancers in which abnormal myeloid cells, called blasts, grow uncontrollably, instead of developing into cells that fight infections and help to heal. JNJ-89853413 (CD33xVδ2) is a bispecific antibody, a type of protein that binds to other proteins and fights off an infection, that binds CD33 protein on AML and MDS blast cells and the Vδ2 chain on Vγ9Vδ2 T-cells. The goal of binding these two cells together is that the T-cells will selectively kill cancer cells. In this study, researchers want to determine the safety and tolerability of JNJ-89853413 and to identify safe doses in participants with relapsed or refractory (R/R) AML or R/R higher-risk types of MDS.
Who can participate?
Participants aged 18 years or older or those who are at least the age of majority diagnosed with R/R AML or R/R higher-risk types of MDS.
What does the study involve?
The study will be conducted in 2 parts:
Part 1 (Dose Escalation): In part 1, participants will get JNJ-89853413 with increasing doses. The goal of increasing the dose is to study the safety of each dose and to establish a safe dose for further evaluation in part 2.
Part 2 (Cohort Expansion): Participants will get treatment at the recommended dose and schedule of JNJ-89853413 established in Part 1.
The study will consist of a screening period followed by a treatment period. During the treatment period, participants will be treated with JNJ-89853413 until the worsening of AML/MDS, serious side effects, or withdrawal from the study. After discontinuation of treatment, participants will be followed to monitor their health.
Safety assessments include blood tests, vital sign measurements, and physical exams. Blood samples will be taken at multiple timepoints to understand how the body responds to treatment.
What are the possible benefits and risks of participating?
Participants may not receive any benefit from taking part in this study, but the information that is learned from the study may help people with AML or MDS in the future.
This is a first-in-human study which means that JNJ-89853413 has not been given to people before. The expected risks for JNJ-89853413, based on how the drug works and results from laboratory studies are unknown.
Possible risks are predicted based on data from other bispecific antibodies and include cytokine release syndrome (CRS), neurologic problems (immune effector cell-associated neurotoxicity syndrome [ICANS]), tumour lysis syndrome (metabolic abnormalities that can occur as a complication from the treatment of cancer), infusion-related reactions (IRRs), allergic reactions, infections, decreases in neutrophil counts, and liver injury. It is unknown whether these side effects will be seen with JNJ-89853413.
The participant information sheet and informed consent form, which will be signed by every participant agreeing to take part in the study, includes a detailed section outlining the risks of participating in the study. Participants may have none, some, or all of the possible side effects listed, and they may be mild, moderate, or severe. To minimise the risk associated with taking part, participants are frequently reviewed for any side effects and other medical events. If they have any side effects, are worried about them, or have any new or unusual symptoms, participants will be encouraged to talk with their study doctor. The study doctor will also be looking out for side effects and will provide appropriate medical care. There may also be side effects that the researchers do not expect or do not know about and that may be serious. Many side effects go away shortly after the intervention ends. However, sometimes side effects can be serious, long-lasting, or permanent.
If a severe side effect or reaction occurs, the study doctor may need to stop the procedure. The study doctor will discuss the best way of managing any side effects with participants. There is always a chance that an unexpected or serious side effect may happen. This can happen to people who take this or any other drug.
Where is the study run from?
Janssen-Cilag International
When is the study starting and how long is it expected to run for?
October 2024 to July 2027
Who is funding the study?
Janssen Research and Development
Who is the main contact?
janssenUKregistryqueries@its.jnj.com
Contact information
Public
Senior Trial Manager
Janssen-Cilag Limited
50-100 Holmers Farm Way
High Wycombe
HP12 4DP
United Kingdom
| Phone | +44 (0)7721 459 573 |
|---|---|
| janssenUKregistryqueries@its.jnj.com |
Principal investigator
NIHR UCLH Clinical Research Facility, 4th Floor
170 Tottenham Court Road
London
W1T 7HA
United Kingdom
Scientific
-
-
-
United Kingdom
| Phone | +44 (0)800 731 8450 or (0)1494 567 444 |
|---|---|
| medinfo@its.jnj.com |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Phase I first-in-human dose-escalation study |
| Secondary study design | Non randomised study |
| Study type | Participant information sheet |
| Scientific title | A phase I, first-in-human, dose escalation study of JNJ-89853413 for relapsed or refractory acute myeloid leukemia or myelodysplastic neoplasms |
| Study objectives | Main objectives - Part 1 (Dose Escalation) & Part 2 (Cohort Expansion): To determine the safety across tested dose regimens and the safer effective dose (recommended phase 2 dose [RP2D]) of JNJ-89853413. Secondary objectives - To assess the Pharmacokinetic (PK) (what the body does to the drug) and immunogenicity (immune response against the drug) of JNJ-89853413. - To evaluate the preliminary clinical activity of JNJ-89853413 in participants with relapsed/refractory* (R/R) acute myeloid leukemia (AML) or relapsed/refractory higher-risk types of myelodysplastic neoplasms (MDS). *Cancer is called relapsed if it returns after treatment and is refractory if it does not respond to treatment. |
| Ethics approval(s) |
Approved 29/12/2024, South Central - Oxford C Research Ethics Committee (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 (0)207 1048144, 207 104 8089, 2071048063; oxfordc.rec@hra.nhs.uk), ref: 24/SC/0351 |
| Health condition(s) or problem(s) studied | Medical condition: Relapsed or Refractory Acute Myeloid Leukemia or Relapsed or Refractory Higher-risk Types of Myelodysplastic Neoplasms Medical condition in lay language: Acute myeloid leukemia (AML) & Myelodysplastic neoplasms (MDS) are cancers in which abnormal myeloid cells, called blasts, grow uncontrollably, instead of developing into cells that fight infections and help to heal. |
| Intervention | Participants will receive JNJ-89853413 in Part 1 (Dose escalation) of the study and the dose levels will be escalated sequentially based on the decisions of the Study Evaluation Team (SET) until the recommended Phase 2 Dose (RP2D) has been identified. Participants in Part 2 (Dose expansion) will receive JNJ-89853413 at the RP2D determined in Part 1. |
| Intervention type | Drug |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | JNJ-89853413 [JNJ-89853413] |
| Primary outcome measure(s) |
1. The number of adverse events by severity measured using data recorded in case report forms from screening until 30 days after the last dose of the study drug (that is approximately 2.5 years) |
| Key secondary outcome measure(s) |
The following secondary outcome measures are measured over approximately 2.5 years: |
| Completion date | 15/07/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | All |
| Target sample size at registration | 100 |
| Key inclusion criteria | 1. Have a diagnosis, per World Health Organization (WHO) 2022 criteria of: 1.1. Relapsed/refractory acute myeloid leukemia (AML) 1.2. Relapsed/refractory moderate-high, high, or very high-risk myelodysplastic neoplasms (MDS) per Molecular International Prognostic Scoring System (IPSS-M) 2. Body weight greater than or equals to (>=) 40 kilograms (kg) 3. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2 4. Have adequate renal function defined as Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Estimated Glomerular Filtration Rate (eGFR) >=40 milligrams per minute (mL/min) 5. Participants must have laboratory parameters in the required range |
| Key exclusion criteria | 1. Has a medical history of clinically significant pulmonary compromise, particularly the need for current supplemental oxygen use to maintain adequate oxygenation 2. Has evidence of an uncontrolled systemic viral, bacterial, or fungal infection 3. Has known allergies, hypersensitivity, or intolerance to the excipients of JNJ-89853413 4. Had major surgery or had significant traumatic injury within 14 days of the planned first dose of JNJ-89853413 5. Has known active central nervous system involvement |
| Date of first enrolment | 02/01/2025 |
| Date of final enrolment | 28/08/2026 |
Locations
Countries of recruitment
- United Kingdom
- England
- Canada
- Spain
Study participating centres
4th Floor, 170 Tottenham Court Road
London
W1T 7HA
United Kingdom
Wilmslow Road
Withington
Manchester
M20 4BX
United Kingdom
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Available on request |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request. The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through the Yale Open Data Access (YODA) Project site at yoda.yale.edu. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
11/02/2025: Internal review.
22/01/2025: The recruitment start date was changed from 28/02/2025 to 02/01/2025.
21/01/2025: The recruitment start date was changed from 06/01/2025 to 28/02/2025.
20/01/2025: Internal review.
11/10/2024: Study's existence confirmed by Health Research Authority (HRA) (UK)
