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Trial record 1 of 1 for:    64619178EDI1001 | Germany
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A Study of JNJ-64619178, an Inhibitor of PRMT5 in Participants With Advanced Solid Tumors, NHL, and Lower Risk MDS

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03573310
Recruitment Status : Recruiting
First Posted : June 29, 2018
Last Update Posted : December 30, 2020
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

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).

Condition or disease Intervention/treatment Phase
Neoplasms Solid Tumor, Adult Non-Hodgkin Lymphoma Myelodysplastic Syndromes Drug: JNJ-64619178 Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 138 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 13, 2018
Estimated Primary Completion Date : July 8, 2022
Estimated Study Completion Date : July 8, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
Drug: JNJ-64619178
JNJ-64619178 capsules to be administered orally.

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




Primary Outcome Measures :
  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 Measures :
  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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03573310


Contacts
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Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com

Locations
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Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
Additional Information:
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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT03573310    
Other Study ID Numbers: CR108485
64619178EDI1001 ( Other Identifier: Janssen Research & Development, LLC )
2018-000067-87 ( EudraCT Number )
First Posted: June 29, 2018    Key Record Dates
Last Update Posted: December 30, 2020
Last Verified: December 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Janssen Research & Development, LLC:
Lower risk MDS
Low risk MDS
Lower-risk MDS
Low-risk MDS
Intermediate 1 risk MDS
Intermediate-1 risk MDS
Additional relevant MeSH terms:
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Myelodysplastic Syndromes
Bone Marrow Diseases
Hematologic Diseases