Clinical trial NCT03573310: A Study of JNJ-64619178, an Inhibitor of PRMT5 in Participants With Advanced Solid Tumors, NHL, and Lower Risk MDS
Official title: A Phase 1, First-in-Human, Open-Label Study of the Safety, Pharmacokinetics, and Pharmacodynamics of JNJ-64619178, an Inhibitor of Protein Arginine Methyltransferase 5 (PRMT5) in Subjects With Advanced Cancers
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Neoplasms
Solid Tumor, Adult
Non-Hodgkin Lymphoma
Myelodysplastic Syndromes
Keywords: Lower risk MDS
Low risk MDS
Lower-risk MDS
Low-risk MDS
Intermediate 1 risk MDS
Intermediate-1 risk MDS
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2018-06-29
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to identify the maximum tolerated dose (MTD) of JNJ-64619178 in participants with relapsed/refractory B cell non-Hodgkin lymphoma (NHL) or advanced solid tumors and also to identify the recommended Phase 2 dose(s) (RP2Ds) of JNJ-64619178 for NHL and advanced solid tumors (Part 1) and to confirm the tolerability of JNJ-64619178 in participants with lower risk myelodysplastic syndromes (MDS) (Part 2).

Detailed description: The study is designed to determine the maximum tolerated dose (MTD) of JNJ-64619178, and to select a dose(s) and regimen(s) that may be used in future clinical development. Study evaluations will include safety, pharmacokinetics, biomarkers and efficacy evaluations (Disease Assessments). Adverse events will be evaluated throughout the study. The study is divided into 4 periods: a screening phase, a pharmacokinetic run-in phase, a treatment phase, and a post treatment follow-up phase. An end-of-treatment visit will be completed less than or equal (\<=) 30 days (+7 days) after the last dose of study drug or prior to the start of a new anticancer therapy, whichever comes first.

Eligibility criteria: Inclusion Criteria:

* B cell non-Hodgkin lymphoma (NHL) or solid tumors, or lower risk MDS
* At least 1 measurable site of disease for B cell-NHL and solid tumors
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
* Adequate organ function
* Women of childbearing potential must have a negative highly sensitive serum (beta-human chorionic gonadotropin \[beta-hCG\]) at screening and prior to the first dose of study drug. Women must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for a period of 90 days after receiving the last dose of study drug

Exclusion Criteria:

* History of, or known, central nervous system (CNS) involvement
* Prior solid organ transplantation
* Either of the following: a) Received an autologous stem cell transplant less than or equal (\<=) 9 months before the first dose of study drug B) Prior treatment with allogenic stem cell transplant
* History of malignancy (other than the disease under study) within 3 years before the first administration of study drug. Exceptions include squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years
* Known allergies, hypersensitivity, or intolerance to JNJ-64619178 or its excipient

Primary outcomes:
measure: Part 1 and Part 2: Number of Participants with Dose-limiting Toxicities (DLTs)
timeFrame: Approximately 3 years
Secondary outcomes:
measure: Part 1 and Part 2: Number of Participants with Adverse Events (AE)
timeFrame: Approximately 3 years
measure: Part 1 and Part 2: Number of Participants with AE by Severity
timeFrame: Approximately 3 years
measure: Part 1 and Part 2: Number of Participants with Abnormal Vital Signs
timeFrame: Approximately 3 years
measure: Part 1 and Part 2: Number of Participants with Laboratory Abnormalities
timeFrame: Approximately 3 years
measure: Part 1 and Part 2: Number of Participants with Electrocardiogram (ECG) Abnormalities
timeFrame: Approximately 3 years
measure: Part 1 and Part 2: Maximum Plasma Concentration (Cmax) of JNJ-64619178
timeFrame: Approximately 3 years
measure: Part 1 and Part 2: Area Under the Plasma Concentration Versus Time Curve From Time Zero to End of Dosing Interval (AUCtau)
timeFrame: Approximately 3 years
measure: Part 1 and Part 2: Minimum Plasma Concentration (Cmin)
timeFrame: Approximately 3 years
measure: Part 1 and Part 2: Plasma Decay Half-Life (t1/2)
timeFrame: Approximately 3 years
measure: Part 1 and Part 2: Volume of Distribution at Steady-State Influenced by the Fraction Absorbed (Vss/F)
timeFrame: Approximately 3 years
measure: Part 1 and Part 2: Apparent Total Systemic Clearance of Drug (CL/F) after Extravascular Administration
timeFrame: Approximately 3 years
measure: Part 1 and Part 2: Accumulation Index (RA)
timeFrame: Approximately 3 years
measure: Part 1 and Part 2: Plasma Concentration of Symmetric Dimethyl-Arginine (SDMA)
timeFrame: Approximately 3 years
measure: Part 1: Percentage of Participants with B cell non-Hodgkin lymphoma (NHL) Showing Overall Response of Partial Response (PR) or Better
timeFrame: Approximately 3 years
measure: Part 1: Percentage of Participants with Solid Tumors Showing Overall Response of PR or Better
timeFrame: Approximately 3 years
measure: Part 1: Duration of Response
timeFrame: Approximately 3 years
measure: Part 1: Clinical Benefit Rate
timeFrame: Approximately 3 years
measure: Part 2: Red Blood Cell (RBC) Transfusion Independence (TI) Rate
timeFrame: Approximately 3 years
measure: Part 2: Overall Improvement Rate
timeFrame: Approximately 3 years
Other outcomes:
Locations:
city: Sarasota
country: United States
facility: Florida Specialist and Cancer Institute
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Houston
country: United States
facility: University of Texas, MD Anderson Cancer Center
state: Texas
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre University Health Network
state: Ontario
city: Düsseldorf
country: Germany
facility: Universitaetsklinikum Duesseldorf
city: Frankfurt/Main
country: Germany
facility: Goethe Universität Frankfurt
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig
city: Haifa
country: Israel
facility: Carmel Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky MC
city: Badalona
country: Spain
facility: Hosp. Univ. Germans Trias I Pujol
city: Barcelona
country: Spain
facility: Hosp Univ Vall D Hebron
city: Madrid
country: Spain
facility: Hosp Univ Fund Jimenez Diaz
city: Pamplona
country: Spain
facility: Clinica Univ. de Navarra
city: Salamanca
country: Spain
facility: Hosp Clinico Univ de Salamanca
city: Sevilla
country: Spain
facility: Hosp. Virgen Del Rocio
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: