En undersøgelse af JNJ-88549968 til behandling af calreticulin (CALR)-muterede myeloproliferative neoplasmer
En første-i-menneskelig undersøgelse af sikkerhed, farmakokinetik og farmakodynamik af JNJ-88549968, et T-celle-omdirigerende bispecifikt antistof for CALR-muterede myeloproliferative neoplasmer
The purpose of this study is to characterize safety and to determine the Recommended Phase 2 Dose (RP2D[s]) and optimal dosing schedule(s) of JNJ-88549968 in part 1 (Dose Escalation); to characterize the safety of JNJ- 88549968 at RP2D(s) in part 2 (Cohort Expansion). For U.S. sites: the purpose of this study is to characterize the safety and to determine the RP2D(s) and optimal dosing schedule(s) of JNJ-88549968 in Part 1 and part 1b (Dose Escalation), and to characterize the safety of JNJ-88549968 at the RP2D(s) in Part 2 and part 2b (Cohort Expansion), when given as monotherapy in essential thrombocythemia (ET) or myelofibrosis (MF), and with ruxolitinib or momelotinib in MF only.
Studieoversigt
Status
Betingelser
Intervention / Behandling
Undersøgelsestype
Tilmelding (Anslået)
Fase
- Fase 1
Kontakter og lokationer
Studiekontakt
- Navn: Study Contact
- Telefonnummer: 844-434-4210
- E-mail: Participate-In-This-Study1@its.jnj.com
Studiesteder
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Alberta
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Calgary, Alberta, Canada, T2N 4N1
- Rekruttering
- Arthur J E Child Comprehensive Cancer Centre
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Ontario
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Toronto, Ontario, Canada, M5G 1Z5
- Rekruttering
- Princess Margaret Cancer Centre University Health Network
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Quebec
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Montreal, Quebec, Canada, H3T 1E2
- Afsluttet
- Jewish General Hospital
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London, Det Forenede Kongerige, SE1 9RT
- Rekruttering
- Guy's and St Thomas' Hospital
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London, Det Forenede Kongerige, NW1 2PG
- Rekruttering
- University College London Hospitals Nhs Foundation Trust
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Oxford, Det Forenede Kongerige, OX3 7LE
- Rekruttering
- Churchill Hospital
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Arizona
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Goodyear, Arizona, Forenede Stater, 85338
- Rekruttering
- City of Hope Phoenix
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California
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Duarte, California, Forenede Stater, 91010
- Rekruttering
- City of Hope
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Colorado
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Aurora, Colorado, Forenede Stater, 80045
- Rekruttering
- UCHealth Cancer Care Anschutz Medical Campus University of Colorado Cancer Center
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Florida
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Tampa, Florida, Forenede Stater, 33612
- Rekruttering
- Moffit Cancer center
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Georgia
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Atlanta, Georgia, Forenede Stater, 30322
- Rekruttering
- Emory University
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Illinois
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Zion, Illinois, Forenede Stater, 60099
- Rekruttering
- City of Hope Chicago
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Michigan
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Ann Arbor, Michigan, Forenede Stater, 48109
- Rekruttering
- University of Michigan
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Grand Rapids, Michigan, Forenede Stater, 49546
- Rekruttering
- Start Midwest
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New Jersey
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East Brunswick, New Jersey, Forenede Stater, 08816
- Rekruttering
- START New Jersey
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New Brunswick, New Jersey, Forenede Stater, 08901
- Rekruttering
- Rutgers Cancer Institute of New Jersey
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New York
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New York, New York, Forenede Stater, 10065
- Rekruttering
- Memorial Sloan Kettering Cancer Center
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The Bronx, New York, Forenede Stater, 10467
- Rekruttering
- Montefiore Medical Center
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North Carolina
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Charlotte, North Carolina, Forenede Stater, 28204
- Rekruttering
- Levine Cancer Institute
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Pennsylvania
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Philadelphia, Pennsylvania, Forenede Stater, 19104
- Rekruttering
- University of Pennsylvania
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South Carolina
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Greenville, South Carolina, Forenede Stater, 29605
- Rekruttering
- Prisma Health
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Tennessee
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Nashville, Tennessee, Forenede Stater, 37203
- Rekruttering
- Sarah Cannon Cancer Institute
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Texas
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Houston, Texas, Forenede Stater, 77030
- Rekruttering
- MD Anderson Cancer Center
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Washington
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Seattle, Washington, Forenede Stater, 98104
- Rekruttering
- Swedish Cancer Institute
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Paris, Frankrig, 75475
- Rekruttering
- Hopital Saint Louis
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Pierre-Bénite, Frankrig, 69495
- Rekruttering
- CH LYON SUD - Hematology
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Toulouse, Frankrig, 31059
- Rekruttering
- Institut Universitaire du Cancer Toulouse Oncopole
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Haifa, Israel, 3436212
- Rekruttering
- Carmel Medical Center
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Jerusalem, Israel, 9112001
- Rekruttering
- Hadassah University Hospita Ein Kerem
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Ramat Gan, Israel, 5266202
- Rekruttering
- Sheba Medical Center
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Tel Aviv, Israel, 64239
- Rekruttering
- Tel Aviv Sourasky Medical Center
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Bologna, Italien, 40138
- Rekruttering
- Policlinico Sant'Orsola Malpighi
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Milan, Italien, 21022
- Rekruttering
- Policlinico di Milano
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Bunkyō City, Japan, 113 8431
- Rekruttering
- Juntendo University Hospital
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Kashiwa, Japan, 277 8577
- Rekruttering
- National Cancer Center Hospital East
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Beijing, Kina, 100032
- Rekruttering
- Peking Union Medical College Hospital
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Hangzhou, Kina, 310002
- Rekruttering
- The First Affiliated Hospital Zhejiang University School of Medicine
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Tianjin, Kina, 301617
- Rekruttering
- Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences
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Badalona, Spanien, 08916
- Rekruttering
- Hosp. Univ. Germans Trias I Pujol
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Valencia, Spanien, 46010
- Rekruttering
- Hosp. Clinico Univ. de Valencia
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Aachen, Tyskland, 52074
- Rekruttering
- Universitaetsklinikum der RWTH Aachen
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Berlin, Tyskland, 12203
- Rekruttering
- Charite Campus Benjamin Franklin
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Essen, Tyskland, 45147
- Rekruttering
- Med. Universitatsklinik Essen
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Hanover, Tyskland, 30625
- Rekruttering
- Medizinische Hochschule Hannover
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Heidelberg, Tyskland, 69120
- Rekruttering
- Universitaetsklinikum Heidelberg
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Regensburg, Tyskland, 93053
- Rekruttering
- Universitaetsklinikum Regensburg
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
- Be greater than or equal to (>=) 18 years of age (or the legal age of majority in the jurisdiction in which the study is taking place, whichever the greater) at the time of informed consent
- Positive for a calreticulin (CALR) driver mutation of essential thrombocythemia (ET) or myelofibrosis (MF)
- Participants with ET and MF with risk characteristics as described in the protocol
- Have an Eastern Cooperative Oncology Group (ECOG) performance status grade of less than or equal to (<=) 2
- For US sites: Eligible for ruxolitinib therapy as per drug label for participants naive to a janus kinase (JAK) inhibitor
Exclusion Criteria:
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Known allergies, hypersensitivity, or intolerance to the excipients of the study treatment
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Concurrent or recently diagnosed or treated malignancies present at the time of participant screening. Exceptions are squamous and basal cell carcinoma of the skin, carcinoma in situ of the cervix, and any malignancy that is considered cured or has minimal risk of recurrence within 1 year of first dose of study treatment in the opinion of both the investigator and sponsor's medical monitor. Participants cured of another malignant disease with no sign of relapse greater than or equal to (>=) 3 years after treatment ended are allowed to enter the study
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Prior solid organ transplantation
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Either of the following regarding hematopoietic stem cell transplantation:
- Prior treatment with allogenic stem cell transplant less than or equal to (<=) 6 months before the first dose of JNJ-88549968 or
- Evidence of graft versus host disease (GVHD) that requires immunosuppressant therapy
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History of clinically significant cardiovascular disease within 6 months prior to the first dose of study treatment
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: N/A
- Interventionel model: Sekventiel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Eksperimentel: Dose Escalation (Part 1), Dose Expansion (Part 2) and Part 1b (US only), Part 2b (US only)
In dose escalation (Part 1), participants will receive JNJ-88549968. For myelofibrosis (MF) participants only, the study will explore a Phase 1b cohort in which the janus kinase (JAK) inhibitor ruxolitinib or momelotinib is started in combination with JNJ-88549968. The dose will be escalated sequentially to determine the recommended phase 2 dose (RP2D) and optimal dosing schedule (s) based on safety, pharmacokinetic, pharmacodynamic, and preliminary assessment of efficacy across several dose regimens. Additional Cohorts may be added to assess different formulation or delivery methods. In dose expansion (Part 2, Part 2b [US only]), participants will receive JNJ-88549968 at the RP2D regimen(s) determined in dose escalation (Part 1, Part 1b [US only]). |
JNJ-88549968 will be administered. For US sites: Ruxolitinib will be administered for participants with MF only. For US sites: Momelotinib will be administered for participants with MF only. |
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Part 1, Part 1b (US Only): Number of Participants With Dose Limiting Toxicity (DLT)
Tidsramme: Approximately up to 35 days after first dose of study treatment
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Number of participants with DLT will be reported. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity. For US only: A DLT is any adverse event attributed to study treatment that meets the criteria for severity and duration and that occurs during the evaluation periods unless it can be incontrovertibly attributed to disease or other extraneous cause such as an accident. |
Approximately up to 35 days after first dose of study treatment
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Part 1, 2, Part 1b (US Only), Part 2b (US Only): Number of Participants with Adverse Events (AEs)
Tidsramme: Up to 2 years
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An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. |
Up to 2 years
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Part 1, 2, Part 1b (US Only), Part 2b (US Only): Number of Participants with Adverse Events (AEs) by Severity
Tidsramme: Up to 2 years
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An adverse event is any untoward medical occurrence in a clinical study participant that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. 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) to grade 5 (death). Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening and Grade 5= death related to adverse event. Cytokine release syndrome (CRS) and associated neurologic toxicity events (immune effector cell-associated neurotoxicity syndrome events [ICANS]) will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines. |
Up to 2 years
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Part 1, 2, Part 1b (US Only), Part 2b (US Only): Serum Concentration of JNJ-88549968
Tidsramme: Up to 2 years
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Serum samples will be analyzed to determine concentrations of JNJ-88549968. |
Up to 2 years
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Part 1, 2, Part 1b (US Only), Part 2b (US Only): Number of Participants With Presence of Anti-Drug Antibodies to JNJ-88549968
Tidsramme: Up to 2 years
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Number of participants with presence of anti-drug antibodies to JNJ-88549968 will be reported. |
Up to 2 years
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Part 1, 2, Part 1b (US Only), Part 2b (US Only): Overall Response Rate
Tidsramme: Up to 2 years
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ORR is defined as the percentage of participants who achieve partial response (PR) and complete response (CR) according to modified International Working Group-Myeloproliferative Neoplasm Research and Treatment (IWG-MRT) criteria and modified European Leukemia Net (ELN) consensus report. |
Up to 2 years
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Part 1, 2, Part 1b (US Only), Part 2b (US Only): Complete Response (CR) Rate
Tidsramme: Up to 2 years
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CR rate is defined as the percentage of participants who achieve a best response of CR according to disease as defined in modified IWG-MRT criteria and modified ELN consensus report. |
Up to 2 years
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Part 1, 2, Part 1b (US Only), Part 2b (US Only): Time to Response (TTR)
Tidsramme: Up to 2 years
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TTR is defined for participants who achieved PR or CR as the time from the first dose of study treatment to first response of PR or CR according to modified IWG-MRT criteria and modified ELN consensus report. |
Up to 2 years
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Part 1, 2, Part 1b (US Only), Part 2b (US Only): Duration of Response (DOR)
Tidsramme: Up to 2 years
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DOR is defined for participants who achieved PR or CR as the time between the date of initial documentation of PR or CR to the date of first documented evidence of disease progression, as defined in modified IWG-MRT criteria and modified ELN consensus report, or death, whichever comes first. |
Up to 2 years
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Part 2, Part 2b (US Only): Change From Baseline in Myeloproliferative Neoplasm (MPN) Symptom Burden
Tidsramme: Baseline up to 2 years
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Change from baseline in MPN symptom burden assessed using patient reported outcome (PRO) questionnaire will be reported in this outcome measure. |
Baseline up to 2 years
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Samarbejdspartnere og efterforskere
Efterforskere
- Studieleder: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Anslået)
Studieafslutning (Anslået)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- 88549968MPN1001
- 2023-505584-36-00 (Registry Identifier: EUCT number)
- 2023 (U.S. NIH-bevilling/kontrakt)
- 88549968MPN1001 (Anden identifikator: Janssen Research & Development, LLC)
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
IPD-planbeskrivelse
The data sharing policy of Johnson & Johnson Innovative Medicine is available at www.innovativemedicine.jnj.com/our-innovation/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
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