Hematologic Neoplasms
Conditions
Brief summary
The purpose of Part 1 (Dose Escalation) of the study is to assess how safe and tolerable JNJ-95804306 is and to find out the most suitable dose (recommended phase 2 dose \[RP2D\]) of JNJ-95804306. The purpose of Part 2 (Dose Expansion) is to further assess the safety of JNJ-95804306 and determine the anti-tumor activity alone and/or when administered in addition to standard of care (SoC) therapy at the putative RP2D(s) regimens in participants with hematological malignancies (cancer that begins in blood-forming tissue, such as the bone marrow, or in the cells of the immune system). For US sites: The purpose of Part 1 (Dose Escalation) of the study is to assess how safe and tolerable JNJ-95804306 is and to find out the most suitable dose (recommended phase 2 dose \[RP2D\]) of JNJ-95804306. The purpose of Part 2 (Dose Expansion) is to further assess the safety of JNJ-95804306 and determine the anti-tumor activity alone at the putative RP2D(s) regimens in participants with hematological malignancies (cancer that begins in blood-forming tissue, such as the bone marrow, or in the cells of the immune system).
Interventions
DRUGJNJ-95804306
JNJ-95804306 will be administered orally.
DRUGAML SoC
AML SoC will be administered subcutaneously/intravenously.
DRUGCLL/SLL SoC
CLL/SLL SoC will be administered orally/ intravenously.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For Arm A: * Have a diagnosis of: Acute myeloid leukemia (AML) per International Consensus Classification (ICC) 2022 or myelodysplastic syndromes (MDS) per world health organization (WHO) 2022 classified as moderate high, high, or very high-risk per the molecular international prognostic scoring system (IPSSM). All participants must have relapsed or refractory disease and have exhausted or are ineligible for standard therapeutic options * Body weight greater than or equal to (\>=) 40 kilograms (kg) * Eastern cooperative oncology group (ECOG) performance status of 0 to 2 For Arm B: * All participants must have relapsed or refractory disease with no other approved therapies available that would be more appropriate in the investigator's judgement. Have a diagnosis of either: Chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL) meeting 2018 International workshop on chronic lymphocytic leukemia (iwCLL) National cancer institute (NCI) working group guidelines (Hallek 2018) that meet the following criteria: a. Participants must have received at least 2 prior lines of therapy; b. Have clinically measurable disease * Body weight \>= 40 kg * ECOG performance status of 0 to 2 * Must sign an Informed consent form (ICF) * For US sites: Have a diagnosis of CLL/SLL that meets iwCLL, NCI Working Group Guidelines which is relapsed or refractory and requires treatment with no other approved therapies available that would be more appropriate in the investigator's judgement. a. Participants must have received at least 2 prior lines of therapy
Exclusion criteria
For Arm A: * Has acute promyelocytic leukemia according to world health organization (WHO) 2022 criteria or known active central nervous system (CNS) involvement of AML/MDS, unless in specific cohort (s) per study evaluation team (SET) decision * Need for supplemental oxygen use to maintain adequate oxygenation * Have evidence of uncontrolled systemic viral, bacterial, or fungal infection. Antimicrobial prophylaxis is permitted * For US sites: Has acute promyelocytic leukemia according to WHO 2022 criteria or known active CNS involvement of AML/MDS For Arm B: * Need for supplemental oxygen use to maintain adequate oxygenation * Have evidence of uncontrolled systemic viral, bacterial, or fungal infection requiring initiation of parenteral treatment as medical intervention * Developed Richter's transformation or prolymphocytic leukemia * Known active CNS or leptomeningeal involvement of CLL/SLL/Non-Hodgkin lymphoma (NHL)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants with Dose Limiting Toxicities (DLTs) | Up to 28 days after first full dose of study drug | DLT is defined as any toxicity that requires discontinuation of treatment; any toxicity resulting in dose reduction of study treatment, any toxicity resulting in a participant receiving less than (\<) 2/3 of their intended dose; any grade 5 toxicity; non-hematologic toxicity (grade 3 or 4); and unacceptable hematologic toxicity. |
| Number of Participants with Adverse Events (AEs) by Severity | Up to 6 years 5 months | An AE is any untoward medical occurrence in a participant administered a pharmaceutical (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the treatment. Severity of AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version (v) 6.0. by using standard grades as follows: Grade 1: Mild; asymptomatic or mild symptoms; Grade 2: Moderate; minimal, local or noninvasive intervention indicated; Grade 3: Severe but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; Grade 4: Life-threatening consequences; and Grade 5: Death related to AE. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| For US sites: Part 1: Number of Participants with Dose Limiting Toxicities (DLTs) | Up to first 28 days after first dose of study drug | DLT is defined as any toxicity that requires discontinuation of treatment; any toxicity resulting in dose reduction of study treatment, any toxicity resulting in a participant receiving less than (\<) 2/3 of their intended dose; any grade 5 toxicity; non-hematologic toxicity (grade 3 or 4); and unacceptable hematologic toxicity. |
| Serum Concentrations of JNJ-95804306 | Up to approximately 6 years 5 months | Serum samples will be analyzed to determine concentrations of JNJ-95804306. |
| Area Under the Curve From Time of Administration until End of Dosing Interval (AUC[t]) of JNJ-95804306 | Up to approximately 6 years 5 months | AUC\[t\] is defined as the area under the plasma concentration time curve during a dosing interval at steady-state. |
| Maximum Plasma Concentration (Cmax) of JNJ-95804306 | Up to approximately 6 years 5 months | Cmax is defined as the maximum serum concentration of JNJ-95804306. |
| Minimum Plasma Concentration (Cmin) of JNJ-95804306 | Up to approximately 6 years 5 months | Cmin is defined as the minimum plasma concentration of JNJ-95804306. |
| Complete Response (CR) in Participants with Acute Myeloid Leukemia (AML) | Up to 6 years 5 months | Complete response (CR) is achieved when a participant with AML has a best response of CR (complete response with partial hematologic recovery \[CRh\] or complete response with incomplete hematologic recovery \[CRi\]) according to the European Leukemia Network (ELN) 2022 criteria. |
| Overall Response (OR) in Participants with Myelodysplastic Syndrome (MDS) | Up to 6 years 5 months | 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 (CR) in Participants with MDS | Up to 6 years 5 months | CR is achieved when a participant with MDS has a best response of CR (including CRh/CRL) according to the IWG 2023 criteria. |
| Overall Response (OR) in Participants with Chronic Lymphocytic Leukemia (CLL) | Up to 6 years 5 months | OR is achieved when a participant with CLL has a CR or PR according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria. |
| Complete Response in Participants with CLL | Up to 6 years 5 months | Complete response as per iwCLL response criteria will be reported. |
| Overall Response in Participants with Non-Hodgkin Lymphoma (NHL) Subtypes Including Small Lymphocytic Lymphoma (SLL) | Up to 6 years 5 months | Overall response is achieved when a participant with NHL subtypes including SLL has a CR or PR according to the revised response criteria for malignant lymphoma. |
| Complete Response in Participants With NHL Subtypes Including SLL | Up to 6 years 5 months | Complete response is achieved when a participant with NHL subtypes including SLL has a best response of CR according to the revised response criteria for malignant lymphoma. |
| Overall Response in WM (Waldenstrom's Macroglobulinemia) | Up to 6 years 5 months | Overall response is achieved when a participant with WM has a CR or PR according to international workshop on waldenstrom's macroglobulinemia 2013 |
| Complete Response in WM | Up to 6 years 5 months | Complete response is achieved when a participant with WM has a best response of CR according to international workshop on waldenstrom's macroglobulinemia 2013. |
| Best Overall Response (BOR) Based on Indication-Specific Criteria | Up to 6 years 5 months | Participants with BOR based on indication-specific criteria will be reported. |
| Duration of Response (DoR) | Up to 6 years 5 months | DOR is defined for responders only, as time from date of initial documentation of a response to the first documented evidence of no response, disease progression, relapse, initiation of a new systemic anti-cancer therapy (besides hematopoietic stem cell transplant \[HSCT\]), or death, whichever comes first. |
| Time to Response (TTR) | Up to 6 years 5 months | TTR is defined for responders only, as the time from the first dose of any study treatment to first qualifying response. |
Countries
Australia, Belgium, Denmark, France, Spain, United Kingdom, United States
Contacts
CONTACTStudy Contact
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Outcome results
None listed