Study of INCB053914 in Subjects With Advanced Malignancies
9. november 2021 opdateret af: Incyte Corporation
A Phase 1/2 Study of INCB053914 in Subjects With Advanced Malignancies
This is an open-label, dose-escalation study of the proviral integration site of Moloney murine leukemia virus (PIM) kinase inhibitor INCB053914 in subjects with advanced malignancies.
The study will be conducted in 4 parts.
Part 1 (monotherapy dose escalation) will evaluate safety and determine the maximum tolerated dose of INCB053914 monotherapy and the recommended phase 2 dose(s) (a tolerated pharmacologically active dose that will be taken forward into the remaining parts of the study).
Part 2 (monotherapy dose expansion) will further evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of the recommended Phase 2 dose(s).
Part 3 (combination dose finding) will evaluate safety of INCB053914 in combination with select standard of care (SOC) agents and will identify the optimal INCB053914 dose in combination with conventional SOC regimens to take forward into Part 4. Part 4 (combination dose expansion) will further evaluate the safety, efficacy and pharmacokinetics of the recommended Phase 2 dose combination(s).
Studieoversigt
Status
Afsluttet
Betingelser
Intervention / Behandling
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
97
Fase
- Fase 2
- Fase 1
Udvidet adgang
Godkendt til salg til offentligheden.
Se udvidet adgangsregistrering.
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
-
-
Arizona
-
Tucson, Arizona, Forenede Stater, 85719
- The University of Arizona Cancer Center
-
-
California
-
Sacramento, California, Forenede Stater, 95817
- UC Davis Comprehensive Cancer Center
-
Santa Monica, California, Forenede Stater, 90095
- UCLA Medical Hematology & Oncology
-
-
Connecticut
-
New Haven, Connecticut, Forenede Stater, 06511
- Yale University
-
-
Florida
-
Jacksonville, Florida, Forenede Stater, 32224
- Mayo Clinic Florida
-
Sarasota, Florida, Forenede Stater, 33916
- Florida Cancer Specialists & Research Institute
-
Tampa, Florida, Forenede Stater, 33612
- H. Lee Moffitt Cancer Center & Research Institute
-
-
Georgia
-
Atlanta, Georgia, Forenede Stater, 30322
- Emory University-Winship Cancer Institute
-
-
Maryland
-
Baltimore, Maryland, Forenede Stater, 21201
- University of Maryland
-
-
Massachusetts
-
Boston, Massachusetts, Forenede Stater, 02215
- Dana-Farber Cancer Center
-
-
Michigan
-
Ann Arbor, Michigan, Forenede Stater, 48109
- University of Michigan Comprehensive Cancer Center
-
-
Nebraska
-
Omaha, Nebraska, Forenede Stater, 69198
- University of Nebraska Medical Center
-
-
Ohio
-
Cincinnati, Ohio, Forenede Stater, 45236
- Oncology Hematology Care Clinical Trials LLC
-
-
Oklahoma
-
Oklahoma City, Oklahoma, Forenede Stater, 73104
- Stephenson Cancer Center
-
-
Tennessee
-
Nashville, Tennessee, Forenede Stater, 37232
- Vanderbilt University Medical Center
-
Nashville, Tennessee, Forenede Stater, 37203
- Tennessee Oncology
-
-
Texas
-
Austin, Texas, Forenede Stater, 78705
- Texas Oncology
-
Tyler, Texas, Forenede Stater, 75702
- Texas Oncology
-
-
Wisconsin
-
Milwaukee, Wisconsin, Forenede Stater, 53226
- Medical College of Wisconsin
-
-
Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år og ældre (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Beskrivelse
Inclusion Criteria:
- Aged 18 years or older
- Confirmed diagnosis of select advanced malignancy
Parts 1 and 2:
- Unresponsive to currently available therapy and there is no standard-of-care therapy available in the judgment of the investigator.
- Not currently a candidate for curative treatment
Parts 3 and 4:
- Subjects with relapsed/refractory AML must have received either induction chemotherapy for AML or hypomethylating agents for hematologic disease before AML.
- Elderly subjects (≥ 65 years) with newly diagnosed AML must be treatment naive and unfit for intensive chemotherapy.
- Myelofibrosis subjects must have been treated with ruxolitinib for ≥ 6 months with a stable dose for ≥ 8 weeks (acceptable doses are 5 mg twice daily [BID] to 25 mg BID).
- Willingness to undergo a pretreatment bone marrow biopsy and/or aspirate, or archival sample obtained since completion of most recent therapy (as appropriate to subjects with existing bone marrow disease or for whom bone marrow examination is a component of disease status assessment)
Eastern Cooperative Oncology Group (ECOG) performance status
- Part 1: 0 or 1
- Parts 2, 3 and 4: 0, 1, or 2
- Life expectancy > 12 weeks or ≥ 24 weeks for Part 3 and Part 4 MF subjects.
Exclusion Criteria:
- Inadequate bone marrow or organ function
- Received an investigational agent within 5 half-lives or 14 days, whichever is longer, prior to receiving the first dose of study drug
- Received non-biologic anticancer medication within 5 half-lives prior to receiving the first dose of study drug (within 6 weeks for mitomycin-C or nitrosoureas), within 28 days for any antibodies or biological therapies
- Prior receipt of a PIM inhibitor
- Any history of disease involving the central nervous system (Part 1). Known active disease involving the central nervous system (Part 2).
- Screening corrected QT interval (QTc) interval > 470 milliseconds
- Radiotherapy within the 2 weeks prior to initiation of treatment
- Chronic or current active infection requiring systemic antibiotic, antifungal, or antiviral treatment
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomiseret
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: Parts 1 and 2: INCB053914 100 mg QD
INCB053914 will be self-administered orally once a day in as a 100mg immediate release tablet as a monotherapy.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth. |
|
Eksperimentel: Parts 3 and 4: INCB053914 + Azacitidine
Azacitidine will be administered at a dose of 75 mg/m2 subcutaneously or via IV per day, as a combination therapy with INCB053914.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth.
Azacitidine dose will be 75 mg/m^2.
Azacitidine will be administered either sub-cutaneously (SC) or intravenously (IV).
Andre navne:
|
|
Eksperimentel: Parts 3 and 4: INCB053914 + I-DAC (Intermediate dose cytarabine)
I-DAC (intermediate dose cytarabine) will be administered at a dose of 1 g/m2 per day as an infusion as a combination therapy with INCB053914.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth.
Cytarabine dose will be 1 g/m^2.
Cytarabine will be administered as an intravenous (IV) infusion.
|
|
Eksperimentel: Parts 3 and 4: INCB053914 + Ruxolitinib
Ruxolitinib will be administered as an oral dose between 5 mg to 25 mg twice per day, as a combination therapy with INCB053914.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth.
Starting dose of ruxolitinib will be the dose the subject was on at study entry Ruxolitinib will be administered by mouth.
|
|
Eksperimentel: Parts 1 and 2: INCB053914 50 mg
INCB053914 will be self-administered orally twice day in as a 50mg immediate release tablet as a monotherapy.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth. |
|
Eksperimentel: Parts 1 and 2: INB053914 65 mg
INCB053914 will be self-administered orally twice day in as a 65mg immediate release tablet as a monotherapy.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth. |
|
Eksperimentel: Parts 1 and 2: INB053914 80 mg
INCB053914 will be self-administered orally twice day in as a 80mg immediate release tablet as a monotherapy.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth. |
|
Eksperimentel: Parts 1 and 2: INB053914 100 mg BID
INCB053914 will be self-administered orally twice day in as a 100mg immediate release tablet as a monotherapy.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth. |
|
Eksperimentel: Parts 1 and 2: INB053914 115 mg
INCB053914 will be self-administered orally twice day in as a 115mg immediate release tablet as a monotherapy.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth. |
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Determination of the Safety and Tolerability of INCB053914 as Measured by the Number of Participants With Adverse Events
Tidsramme: Approximately 7 months
|
Approximately 7 months
|
|
|
Part 4 Only : Determination of the Efficacy of INCB053914 in Combination With the Intermediate-dose Cytarabine (I DAC) in Subjects With Relapsed or Refractory Acute Myeloid Leukemia (AML) Based on Objective Remission Rate (ORR)
Tidsramme: Approximately 2 months
|
The primary efficacy endpoint of ORR in patients with AML who received INCB053914 in combination with cytarabine in Part 4 was not assessed because Part 4 was not opened for enrollment owing to this combination regimen not being tolerated in Part 3.
|
Approximately 2 months
|
|
Part 4 Only : Determination of the Efficacy of INCB053914 in Combination With Azacitidine in Subjects With Newly Diagnosed AML Who Are 65 Years or Older and Unfit for Intensive Chemotherapy Based on ORR
Tidsramme: Approximately 6 months
|
The primary efficacy endpoint of ORR in patients with AML who received INCB053914 plus azacitidine in Part 4 was not performed due to limited enrollment as a result of early study termination.
|
Approximately 6 months
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Evaluation of Phosphorylated BCL--2 Associated Death Promoter Protein (pBAD)
Tidsramme: 1 month
|
Percent Inhibition of pBAD at the C1D15 trough from the pBAD at pre-dose by ex vivo cellular assay
|
1 month
|
|
Pharmacokinetics: Tmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine
Tidsramme: Cycle 1 Day 5
|
Cycle 1 Day 5
|
|
|
Pharmacokinetics: AUCtau of Combination Treatment Group A INCB053914 50 mg + Cytarabine
Tidsramme: Cycle 1 Day 5
|
Cycle 1 Day 5
|
|
|
Pharmacokinetics: Cl/F of Combination Treatment Group A INCB053914 50 mg + Cytarabine
Tidsramme: Cycle 1 Day 5
|
Cycle 1 Day 5
|
|
|
Pharmacokinetics: Cmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine
Tidsramme: Cycle 1 Day 5
|
Cycle 1 Day 5
|
|
|
Pharmacokinetics: Cmin of Combination Treatment Group A INCB053914 50 mg + Cytarabine
Tidsramme: Cycle 1 Day 5
|
Cycle 1 Day 5
|
|
|
Pharmacokinetics: Tmax of Combination Group B INCB053914 80 mg + Azatcitidine
Tidsramme: Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: AUCtau of Combination Group B INCB053914 80 mg + Azatcitidine
Tidsramme: Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: Cl/F of Combination Group B INCB053914 80 mg + Azatcitidine
Tidsramme: Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: Cmax of Combination Group B INCB053914 80 mg + Azatcitidine
Tidsramme: Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: Cmin of Combination Group B INCB053914 80 mg + Azatcitidine
Tidsramme: Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: Tmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Tidsramme: Regimen 2 Week 4
|
Regimen 2 Week 4
|
|
|
Pharmacokinetics: AUCtau of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Tidsramme: Regimen 2 Week 4
|
Regimen 2 Week 4
|
|
|
Pharmacokinetics: Cl/F of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Tidsramme: Regimen 2 Week 4
|
Regimen 2 Week 4
|
|
|
Pharmacokinetics: Cmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Tidsramme: Regimen 2 Week 4
|
Regimen 2 Week 4
|
|
|
Pharmacokinetics: Cmin of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Tidsramme: Regimen 2 Week 4
|
Regimen 2 Week 4
|
|
|
Pharmacokinetics: Tmax of INCB053914 Monotherapy
Tidsramme: Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: AUCtau of INCB053914 Monotherapy
Tidsramme: Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: CL/F of INCB053914 Monotherapy
Tidsramme: Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: Cmax of INCB053914 Monotherapy
Tidsramme: Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: Ctau of INCB053914 Monotherapy
Tidsramme: Cycle 1 Day 8
|
Cycle 1 Day 8
|
Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart (Faktiske)
29. december 2015
Primær færdiggørelse (Faktiske)
11. august 2020
Studieafslutning (Faktiske)
11. august 2020
Datoer for studieregistrering
Først indsendt
26. oktober 2015
Først indsendt, der opfyldte QC-kriterier
26. oktober 2015
Først opslået (Skøn)
27. oktober 2015
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
8. december 2021
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
9. november 2021
Sidst verificeret
1. november 2021
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- INCB 53914-101
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret enhedsprodukt
Ingen
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .
Kliniske forsøg med Faste tumorer
-
Memorial Sloan Kettering Cancer CenterRekrutteringSolid tumor | Solid tumor, voksen | Solid tumor, uspecificeret, voksenForenede Stater
-
Memorial Sloan Kettering Cancer CenterLincoln Medical and Mental Health CenterRekrutteringSolid tumor | Solid tumor, voksen | Solid tumor, uspecificeret, voksenForenede Stater, Puerto Rico
-
Memorial Sloan Kettering Cancer CenterLincoln Medical and Mental Health CenterRekrutteringSolid tumor | Solid tumor, voksen | Solid tumor, uspecificeret, voksenForenede Stater, Puerto Rico
-
Memorial Sloan Kettering Cancer CenterRekrutteringSolid tumor | Solid tumor, voksenForenede Stater
-
Avelos Therapeutics Inc.RekrutteringSolid tumor | Solid tumorkræft | Solid tumor, voksen | Solid tumor, uspecificeret, voksen | Tumor, fast | Solid tumor i avanceret scene | Faste tumorer, der er ildfast til standardterapiKorea, Republikken
-
Sorrento Therapeutics, Inc.Trukket tilbageSolid tumor | Recidiverende solid tumor | Refraktær tumor
-
Neurogene Inc.Merck Sharp & Dohme LLCAfsluttetSolid tumor | Avanceret solid tumorForenede Stater, Australien, Canada
-
EMD Serono Research & Development Institute, Inc.Merck KGaA, Darmstadt, GermanyAfsluttetSolid tumor | Avanceret solid tumorSpanien, Forenede Stater, Holland, Det Forenede Kongerige
-
Impact Therapeutics, Inc.RekrutteringSolid tumor | Avanceret solid tumorKina, Australien, Taiwan, Forenede Stater
-
Partner Therapeutics, Inc.Trukket tilbageSolid tumor | Solid tumor, voksenForenede Stater
Kliniske forsøg med INCB053914
-
Incyte CorporationAfsluttetRefraktært diffust stort B-cellet lymfom | Residiverende diffust stort B-cellet lymfomForenede Stater
-
Medical College of WisconsinTrukket tilbageRefraktær Myelom | Tilbagefaldende myelomatose