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JOURNAL ONKOLOGIE – STUDIE

A Study of JNJ-64619178, an Inhibitor of PRMT5 in Participants With Advanced Solid Tumors, NHL, and Lower Risk MDS

Rekrutierend

NCT-Nummer:
NCT03573310

Studienbeginn:
Juli 2018

Letztes Update:
26.03.2021

Wirkstoff:
JNJ-64619178

Indikation (Clinical Trials):
Myelodysplastic Syndromes

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
Janssen Research & Development, LLC

Collaborator:
-

Studienleiter

Janssen Research & Development, LLC Clinical Trial
Study Director
Janssen Research & Development, LLC

Kontakt

Studienlocations
(3 von 22)

Universitaetsklinikum Duesseldorf
40225 Düsseldorf
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Goethe Universität Frankfurt
60590 Frankfurt/Main
(Hessen)
GermanyRekrutierend» Google-Maps
Universitatsklinikum Leipzig
04103 Leipzig
(Sachsen)
GermanyRekrutierend» Google-Maps
Klinikum rechts der Isar an der Technischen Universität München
81675 München
(Bayern)
GermanyZurückgezogen» Google-Maps
Florida Specialist and Cancer Institute
34232 Sarasota
United StatesRekrutierend» Google-Maps
Massachusetts General Hospital
02114 Boston
United StatesRekrutierend» Google-Maps
Beth Israel Deaconess Medical Center
02215 Boston
United StatesZurückgezogen» Google-Maps
University of Massechusetts Medical School
01655 Worcester
United StatesZurückgezogen» Google-Maps
Ohio State University
43210 Columbus
United StatesRekrutierend» Google-Maps
Baylor Scott and White Health
75246 Dallas
United StatesZurückgezogen» Google-Maps
University of Texas, MD Anderson Cancer Center
77030 Houston
United StatesAbgeschlossen» Google-Maps
St. Paul's Hospital
V6E 1M7 Vancouver
CanadaNoch nicht rekrutierend» Google-Maps
Hosp. Univ. Germans Trias I Pujol
08916 Badalona
SpainRekrutierend» Google-Maps
Hosp. Clinico Univ. de Salamanca
37007 Salamanca
SpainRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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

Studien-Rationale

Primary outcome:

1. Part 1 and Part 2: Number of Participants with Dose-limiting Toxicities (DLTs) (Time Frame - Approximately 3 years):
DLTs are defined as certain non-hematologic and hematologic toxicities of Grade 3 or higher.



Secondary outcome:

1. Part 1 and Part 2: Number of Participants with Adverse Events (AE) (Time Frame - Approximately 3 years):
AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship.

2. Part 1 and Part 2: Number of Participants with AE by Severity (Time Frame - Approximately 3 years):
Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). Severity scale ranges from Grade 1 (Mild) to Grade 4 (Life-threatening). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.

3. Part 1 and Part 2: Number of Participants with Abnormal Vital Signs (Time Frame - Approximately 3 years):
Number of participants with abnormality in vital signs (temperature, pulse/heart rate, and blood pressure) will be reported.

4. Part 1 and Part 2: Number of Participants with Laboratory Abnormalities (Time Frame - Approximately 3 years):
Number of participants with laboratory abnormalities (serum chemistry, hematology, and coagulation, and disease-related laboratory abnormalities) will be reported.

5. Part 1 and Part 2: Number of Participants with Electrocardiogram (ECG) Abnormalities (Time Frame - Approximately 3 years):
Number of participants with electrocardiogram(ECG) abnormalities will be reported.

6. Part 1 and Part 2: Maximum Plasma Concentration (Cmax) of JNJ-64619178 (Time Frame - Approximately 3 years):
Cmax is the maximum observed plasma concentration.

7. Part 1 and Part 2: Area Under the Plasma Concentration Versus Time Curve From Time Zero to End of Dosing Interval (AUCtau) (Time Frame - Approximately 3 years):
AUCtau is the measure of the plasma drug concentration from time zero to end of dosing interval.

8. Part 1 and Part 2: Minimum Plasma Concentration (Cmin) (Time Frame - Approximately 3 years):
Cmin is the minimum observed plasma concentration.

9. Part 1 and Part 2: Plasma Decay Half-Life (t1/2) (Time Frame - Approximately 3 years):
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

10. Part 1 and Part 2: Volume of Distribution at Steady-State Influenced by the Fraction Absorbed (Vss/F) (Time Frame - Approximately 3 years):
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady state which is estimated by (D/AUC[0-infinity])* (AUMC[0-infinity])/(AUC[0-infinity]) where D is the dose of study drug, AUMC(0-infinity) is the area under the first moment curve extrapolated to infinity and AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time. All these parameters will be assessed as influenced by the fraction absorbed.

11. Part 1 and Part 2: Apparent Total Systemic Clearance of Drug (CL/F) after Extravascular Administration (Time Frame - Approximately 3 years):
Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

12. Part 1 and Part 2: Accumulation Index (RA) (Time Frame - Approximately 3 years):
Accumulation Index (RA) is calculated as AUC (0-24) value at steady state divided by AUC (0-24) value after first dose.

13. Part 1 and Part 2: Plasma Concentration of Symmetric Dimethyl-Arginine (SDMA) (Time Frame - Approximately 3 years):
Plasma concentration of symmetric dimethyl-arginine (SDMA) will be evaluated.

14. Part 1: Percentage of Participants with B cell non-Hodgkin lymphoma (NHL) Showing Overall Response of Partial Response (PR) or Better (Time Frame - Approximately 3 years):
Overall response rate (ORR) is defined as the percentage of participants who have a PR or better. Per Lugano classification, PR is defined as greater than or equal (>=) 50 percent (%) decrease in size of target lesions.

15. Part 1: Percentage of Participants with Solid Tumors Showing Overall Response of PR or Better (Time Frame - Approximately 3 years):
Overall response rate (ORR) is defined as the percentage of participants who have a PR or better. PR criteria in solid tumors (RECIST) is >= 30 percent (%) decrease in the sum of the diameters of all index lesions compared with baseline in 2 observations at least 4 weeks apart, in absence of new lesions or unequivocal progression of non-index lesions.

16. Part 1: Duration of Response (Time Frame - Approximately 3 years):
Duration of response (DOR) will be calculated from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease (PD), as defined in the disease-specific response criteria, or death due to any cause, whichever occurs first. PD (per RECIST 1.1) defined as at least 20% increase in the sum of the longest diameters of index lesions or unequivocal progression of non-index lesions. Per Lugano classification, PD: target lesions larger; clear progression of non-target lesions; or new tumor lesions; new or recurrent bone marrow involvement; splenomegaly + 2 centimeter (cm) or +50%.

17. Part 1: Clinical Benefit Rate (Time Frame - Approximately 3 years):
Clinical benefit rate is defined as percentage of participants who have a complete response (CR), PR and sustained stable disease of 12 weeks or more. Sustained stable disease of 12 weeks or more is defined as participants with stable disease assessment maintained for about 12 weeks or longer from baseline. Per Lugano classification CR is defined as no detectable disease by computed tomography (CT) or positron emission tomography (PET)/CT scan. Evaluation criteria as per RECIST 1.1 for CR is defined as disappearance of all lesions in 2 consecutive observations not less than 4 weeks apart.

18. Part 2: Red Blood Cell (RBC) Transfusion Independence (TI) Rate (Time Frame - Approximately 3 years):
Percentage of participants with TI, defined as being without any transfusion during any consecutive 8 weeks (56 days) between the first dose of study drug and treatment discontinuation.

19. Part 2: Overall Improvement Rate (Time Frame - Approximately 3 years):
Overall improvement rate is defined as the percentage of participants achieving complete remission (bone marrow: less than or equal to (<=)5% myeloblasts with normal maturation of all cell lines; Peripheral blood: hemoglobin >=11 gram per deciliter (g/dL); platelets >=100*109/liter(L); neutrophils >=1.0*109/L; blasts, 0%), partial remission (All complete remission criteria if abnormal before treatment except: Bone marrow blasts decreased by >=50% over pretreatment but still >5% Cellularity and morphology not relevant), or hematologic improvement (HI) (Erythroid response [pretreatment, <11 g/dL]; Platelet response (pretreatment, <100*10^9/L); Neutrophil response (pretreatment, <1*10^9/L); Progression or relapse after HI) according to modified International Working Group (IWG) criteria.

Studien-Arme

  • Experimental: Part 1: Dose escalation and RP2D Selection
    Participants with solid tumors or non-Hodgkin lymphoma (NHL) will receive JNJ-64619178 orally as per the assigned sequential cohorts and doses will be escalated based on the review of all available data including, but not limited to, pharmacokinetic, pharmacodynamic, safety, and clinical activity. One or more recommended Phase 2 dose(s) (RP2Ds) may be determined for further exploration.
  • Experimental: Part 2:Dose Confirmation and Expansion
    Participants with myelodysplastic syndromes (MDS) will receive JNJ-64619178 at a dose less than or equal to the RP2D selected in Part 1 for 24 weeks, or longer if there is evidence of clinical benefit. The dose level of JNJ-64619178 may be adjusted based on observed toxicities.

Geprüfte Regime

  • JNJ-64619178:
    JNJ-64619178 capsules to be administered orally.

Quelle: ClinicalTrials.gov


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