Leukemia, Myeloid, Acute, Myelodysplastic Neoplasms
Conditions
Brief summary
The purpose of Part 1 (Dose Escalation) of the study is to assess the effective dose (recommended Phase 2 dose\[s\] \[RP2Ds\]) that can be safely administered, and dosing regimens of JNJ-90189892 in participants with relapsed or refractory (R/R) acute myeloid leukemia (AML) or R/R higher-risk type of myelodysplastic neoplasms (MDS \[type of cancer of the blood and bone marrow, which does not respond to treatment or comes back after treatment\]). The purpose of Part 2 (Cohort Expansion) is to further assess the safety, tolerability and efficacy in participants with R/R AML or higher-risk types of MDS at the RP2D regimen(s). The purpose of Part 3 and 4 is to assess the effective dose (recommended Phase 2 combination dose \[RP2CD\]) that can be safely administered, and dosing regimens of JNJ-90189892 in combination with azacitadine (AZA) + venetoclax (VEN) in participants with R/R AML (part 3) and newly diagnosed (ND) AML (part 4).
Interventions
DRUGJNJ-90189892
JNJ-90189892 will be administered.
DRUGAzacitadine (AZA)
AZA will be administered.
DRUGVenetoclax (VEN)
VEN will be administered.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A. For Parts 1, 2, and 3: Have a diagnosis, per the world health organization (WHO) 2022 criteria, of (a) Parts 1, 2, and 3: Acute myeloid leukemia (AML) or (b) Parts 1 and 2: Moderate high, high, or very high-risk myelodysplastic neoplasms (MDS) per Molecular International Prognostic Scoring System (IPSS-M); B. For Part 4 only: Previously untreated acute myeloid leukemia (AML) per the WHO 2022 criteria * Body weight that is greater than or equals to (\>=) 40 kg * Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 * Have adequate renal function defined as Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Estimated Glomerular Filtration Rate (eGFR) \>=40 milligrams per minute (mL/min) computed with the calculator on the national kidney foundation website * Participants must have laboratory parameters in the required range
Exclusion criteria
* Has a medical history of clinically significant pulmonary compromise, particularly the current need for supplemental oxygen use to maintain adequate oxygenation * Has evidence of uncontrolled systemic viral, bacterial, or fungal infection. Antimicrobial prophylaxis is permitted * All participants- Has known allergies, hypersensitivity, or intolerance to JNJ-90189892 or its excipients; Parts 3 and 4- Has known allergies, hypersensitivity, or intolerance to venetoclax (VEN), azacitadine (AZA), or their excipients * Had major surgery or had significant traumatic injury within 14 days of planned first dose of JNJ-90189892 * Had a prior or concurrent second malignancy with natural history or treatment likely to interfere with any study endpoints of safety or the efficacy of the study treatment * Has known active central nervous system involvement
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Adverse events (AEs) by Severity | From screening untill 30 days after last dose of study drug (that is approximately 2.5 years) | An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event. |
| Part 1: Number of Participants with Dose-Limiting Toxicity (DLTs) | At least 14 days | DLT is defined as any toxicity that requires discontinuation of treatment, any Grade 5 toxicity; Non-hematologic toxicity (Grade 3 or 4) and Hematologic toxicity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Concentration of JNJ-90189892 | Up to approximately 2.5 years | Serum samples will be analyzed to determine concentrations of JNJ-90189892. |
| Area Under the Curve Over a Dosing Interval (AUC tau) of JNJ-90189892 | Up to approximately 2.5 years | AUC tau is the total observed plasma concentration of JNJ-90189892 in the body during the time between doses. AUCtau of JNJ-90189892 will be reported. |
| Maximum Observed Plasma Concentration (Cmax) of JNJ-90189892 | Up to approximately 2.5 years | Cmax is the maximum observed plasma concentration of JNJ-90189892. Cmax of JNJ-90189892 will be reported. |
| Minimum Observed Plasma Concentration (Cmin) of JNJ-90189892 | Up to approximately 2.5 years | Cmin is the minimum observed plasma concentration of JNJ-90189892. Cmin of JNJ-90189892 will be reported. |
| Number of Participants with Presence of Anti-JNJ-90189892 Antibodies | Up to approximately 2.5 years | Participants with presence of anti-JNJ-90189892 antibodies will be reported. |
| Complete Response (CR) in Acute Myeloid Leukemia (AML) | Up to approximately 2.5 years | CR is achieved when a participant has a best response of CR (including complete response with partial hematologic recovery \[CRh\] or complete response with incomplete hematologic recovery \[CRi\]) according to the European Leukemia Network (ENL) 2022 criteria. |
| Overall Response (OR) in Myelodysplastic Neoplasms (MDS) | Up to approximately 2.5 years | OR is achieved when a participant with MDS has a CR (any type, that is CRh or complete response with limited count recovery \[CRL\]), partial response (PR), or hematologic improvement (HI) according to the International Working Group (IWG) 2023 criteria. |
| Complete Response in MDS | Up to approximately 2.5 years | CR is achieved when a participant has a best response of CR (including CRh/CRL) according to the IWG 2023 criteria. |
| Duration of Response (DOR) | Up to approximately 2.5 years | DOR is defined for responsders only, as time from date of initial documentation of a response to the first documented evidence of no reponse, disease progression, relapse, initation of a new systemic anti-cancer therapy (besides hematopoietic stem cell transplant \[HSCT\]), or death, whichever comes first. |
| Time to Response (TTR) | Up to approximately 2.5 years | TTR is defined for responders, as the time from the first dose of study drug to first qualifying response. |
| Number of Participants Achieving Transfusion Independence | Up to approximately 2.5 years | Transfusion independence is defined as the absence of red blood cell (RBC) and platelet transfusions for 8 weeks or longer after starting study treatment for participants with AML and 16 weeks or longer for participants with MDS. |
| Part 4 Only: Overall Survival (OS) | Up to approximately 2.5 years | OS is defined as the time from the date of first dose of study treatment to the date of death due to any cause. |
| Part 4 Only: Event-Free Survival (EFS) | Up to approximately 2.5 years | EFS is defined as the time from the date of first dose of study treatment to the date of first documented evidence of treatment failure, relapse or death due to any cause, whichever occurs first. |
Countries
Australia, France, Spain
Contacts
CONTACTStudy Contact
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Outcome results
None listed