Study of INCB053914 in Subjects With Advanced Malignancies
tiistai 9. marraskuuta 2021 päivittänyt: 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).
Tutkimuksen yleiskatsaus
Tila
Lopetettu
Ehdot
Opintotyyppi
Interventio
Ilmoittautuminen (Todellinen)
97
Vaihe
- Vaihe 2
- Vaihe 1
Laajennettu käyttöoikeus
Hyväksytty myytävänä yleisölle.
Katso laajennettu käyttöoikeustietue.
Yhteystiedot ja paikat
Tässä osiossa on tutkimuksen suorittajien yhteystiedot ja tiedot siitä, missä tämä tutkimus suoritetaan.
Opiskelupaikat
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Arizona
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Tucson, Arizona, Yhdysvallat, 85719
- The University of Arizona Cancer Center
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California
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Sacramento, California, Yhdysvallat, 95817
- UC Davis Comprehensive Cancer Center
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Santa Monica, California, Yhdysvallat, 90095
- UCLA Medical Hematology & Oncology
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Connecticut
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New Haven, Connecticut, Yhdysvallat, 06511
- Yale University
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Florida
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Jacksonville, Florida, Yhdysvallat, 32224
- Mayo Clinic Florida
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Sarasota, Florida, Yhdysvallat, 33916
- Florida Cancer Specialists & Research Institute
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Tampa, Florida, Yhdysvallat, 33612
- H. Lee Moffitt Cancer Center & Research Institute
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Georgia
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Atlanta, Georgia, Yhdysvallat, 30322
- Emory University-Winship Cancer Institute
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Maryland
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Baltimore, Maryland, Yhdysvallat, 21201
- University of Maryland
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Massachusetts
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Boston, Massachusetts, Yhdysvallat, 02215
- Dana-Farber Cancer Center
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Michigan
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Ann Arbor, Michigan, Yhdysvallat, 48109
- University Of Michigan Comprehensive Cancer Center
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Nebraska
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Omaha, Nebraska, Yhdysvallat, 69198
- University of Nebraska Medical Center
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Ohio
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Cincinnati, Ohio, Yhdysvallat, 45236
- Oncology Hematology Care Clinical Trials LLC
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Oklahoma
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Oklahoma City, Oklahoma, Yhdysvallat, 73104
- Stephenson Cancer Center
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Tennessee
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Nashville, Tennessee, Yhdysvallat, 37232
- Vanderbilt University Medical Center
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Nashville, Tennessee, Yhdysvallat, 37203
- Tennessee Oncology
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Texas
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Austin, Texas, Yhdysvallat, 78705
- Texas Oncology
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Tyler, Texas, Yhdysvallat, 75702
- Texas Oncology
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Wisconsin
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Milwaukee, Wisconsin, Yhdysvallat, 53226
- Medical College of Wisconsin
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Osallistumiskriteerit
Tutkijat etsivät ihmisiä, jotka sopivat tiettyyn kuvaukseen, jota kutsutaan kelpoisuuskriteereiksi. Joitakin esimerkkejä näistä kriteereistä ovat henkilön yleinen terveydentila tai aiemmat hoidot.
Kelpoisuusvaatimukset
Opintokelpoiset iät
18 vuotta ja vanhemmat (Aikuinen, Vanhempi Aikuinen)
Hyväksyy terveitä vapaaehtoisia
Ei
Sukupuolet, jotka voivat opiskella
Kaikki
Kuvaus
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
Opintosuunnitelma
Tässä osiossa on tietoja tutkimussuunnitelmasta, mukaan lukien kuinka tutkimus on suunniteltu ja mitä tutkimuksella mitataan.
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Jako: Ei satunnaistettu
- Inventiomalli: Yksittäinen ryhmätehtävä
- Naamiointi: Ei mitään (avoin tarra)
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
|---|---|
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Kokeellinen: 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. |
|
Kokeellinen: 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).
Muut nimet:
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Kokeellinen: 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.
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Kokeellinen: 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.
|
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Kokeellinen: 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. |
|
Kokeellinen: 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. |
|
Kokeellinen: 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. |
|
Kokeellinen: 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. |
|
Kokeellinen: 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. |
Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
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Determination of the Safety and Tolerability of INCB053914 as Measured by the Number of Participants With Adverse Events
Aikaikkuna: Approximately 7 months
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Approximately 7 months
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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)
Aikaikkuna: Approximately 2 months
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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.
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Approximately 2 months
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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
Aikaikkuna: Approximately 6 months
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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.
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Approximately 6 months
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Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
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Evaluation of Phosphorylated BCL--2 Associated Death Promoter Protein (pBAD)
Aikaikkuna: 1 month
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Percent Inhibition of pBAD at the C1D15 trough from the pBAD at pre-dose by ex vivo cellular assay
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1 month
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Pharmacokinetics: Tmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine
Aikaikkuna: Cycle 1 Day 5
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Cycle 1 Day 5
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Pharmacokinetics: AUCtau of Combination Treatment Group A INCB053914 50 mg + Cytarabine
Aikaikkuna: Cycle 1 Day 5
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Cycle 1 Day 5
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Pharmacokinetics: Cl/F of Combination Treatment Group A INCB053914 50 mg + Cytarabine
Aikaikkuna: Cycle 1 Day 5
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Cycle 1 Day 5
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Pharmacokinetics: Cmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine
Aikaikkuna: Cycle 1 Day 5
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Cycle 1 Day 5
|
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Pharmacokinetics: Cmin of Combination Treatment Group A INCB053914 50 mg + Cytarabine
Aikaikkuna: Cycle 1 Day 5
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Cycle 1 Day 5
|
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Pharmacokinetics: Tmax of Combination Group B INCB053914 80 mg + Azatcitidine
Aikaikkuna: Cycle 1 Day 8
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Cycle 1 Day 8
|
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Pharmacokinetics: AUCtau of Combination Group B INCB053914 80 mg + Azatcitidine
Aikaikkuna: Cycle 1 Day 8
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Cycle 1 Day 8
|
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Pharmacokinetics: Cl/F of Combination Group B INCB053914 80 mg + Azatcitidine
Aikaikkuna: Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: Cmax of Combination Group B INCB053914 80 mg + Azatcitidine
Aikaikkuna: Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: Cmin of Combination Group B INCB053914 80 mg + Azatcitidine
Aikaikkuna: Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: Tmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Aikaikkuna: Regimen 2 Week 4
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Regimen 2 Week 4
|
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Pharmacokinetics: AUCtau of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Aikaikkuna: Regimen 2 Week 4
|
Regimen 2 Week 4
|
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Pharmacokinetics: Cl/F of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Aikaikkuna: Regimen 2 Week 4
|
Regimen 2 Week 4
|
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Pharmacokinetics: Cmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Aikaikkuna: Regimen 2 Week 4
|
Regimen 2 Week 4
|
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Pharmacokinetics: Cmin of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Aikaikkuna: Regimen 2 Week 4
|
Regimen 2 Week 4
|
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Pharmacokinetics: Tmax of INCB053914 Monotherapy
Aikaikkuna: Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
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Pharmacokinetics: AUCtau of INCB053914 Monotherapy
Aikaikkuna: Cycle 1 Day 8
|
Cycle 1 Day 8
|
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Pharmacokinetics: CL/F of INCB053914 Monotherapy
Aikaikkuna: Cycle 1 Day 8
|
Cycle 1 Day 8
|
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Pharmacokinetics: Cmax of INCB053914 Monotherapy
Aikaikkuna: Cycle 1 Day 8
|
Cycle 1 Day 8
|
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Pharmacokinetics: Ctau of INCB053914 Monotherapy
Aikaikkuna: Cycle 1 Day 8
|
Cycle 1 Day 8
|
Yhteistyökumppanit ja tutkijat
Täältä löydät tähän tutkimukseen osallistuvat ihmiset ja organisaatiot.
Sponsori
Opintojen ennätyspäivät
Nämä päivämäärät seuraavat ClinicalTrials.gov-sivustolle lähetettyjen tutkimustietueiden ja yhteenvetojen edistymistä. National Library of Medicine (NLM) tarkistaa tutkimustiedot ja raportoidut tulokset varmistaakseen, että ne täyttävät tietyt laadunvalvontastandardit, ennen kuin ne julkaistaan julkisella verkkosivustolla.
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Todellinen)
Tiistai 29. joulukuuta 2015
Ensisijainen valmistuminen (Todellinen)
Tiistai 11. elokuuta 2020
Opintojen valmistuminen (Todellinen)
Tiistai 11. elokuuta 2020
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Maanantai 26. lokakuuta 2015
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Maanantai 26. lokakuuta 2015
Ensimmäinen Lähetetty (Arvio)
Tiistai 27. lokakuuta 2015
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Keskiviikko 8. joulukuuta 2021
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Tiistai 9. marraskuuta 2021
Viimeksi vahvistettu
Maanantai 1. marraskuuta 2021
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Avainsanat
Muita asiaankuuluvia MeSH-ehtoja
- Neoplasmat
- Huumeiden fysiologiset vaikutukset
- Farmakologisen vaikutuksen molekyylimekanismit
- Infektiota estävät aineet
- Viruksenvastaiset aineet
- Entsyymin estäjät
- Antimetaboliitit, antineoplastiset
- Antimetaboliitit
- Antineoplastiset aineet
- Immunosuppressiiviset aineet
- Immunologiset tekijät
- Atsasitidiini
- Sytarabiini
Muut tutkimustunnusnumerot
- INCB 53914-101
Lääke- ja laitetiedot, tutkimusasiakirjat
Tutkii yhdysvaltalaista FDA sääntelemää laitetuotetta
Ei
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