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Study of INCB053914 in Subjects With Advanced Malignancies

9. November 2021 aktualisiert von: 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).

Studienübersicht

Status

Beendet

Bedingungen

Intervention / Behandlung

Studientyp

Interventionell

Einschreibung (Tatsächlich)

97

Phase

  • Phase 2
  • Phase 1

Erweiterter Zugriff

Genehmigt zum Verkauf an die Öffentlichkeit. Siehe erweiterter Zugriffsdatensatz.

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienorte

  • Vereinigte Staaten
    • Arizona
      • Tucson, Arizona, Vereinigte Staaten, 85719
        • The University of Arizona Cancer Center
    • California
      • Sacramento, California, Vereinigte Staaten, 95817
        • UC Davis Comprehensive Cancer Center
      • Santa Monica, California, Vereinigte Staaten, 90095
        • UCLA Medical Hematology & Oncology
    • Connecticut
      • New Haven, Connecticut, Vereinigte Staaten, 06511
        • Yale University
    • Florida
      • Jacksonville, Florida, Vereinigte Staaten, 32224
        • Mayo Clinic Florida
      • Sarasota, Florida, Vereinigte Staaten, 33916
        • Florida Cancer Specialists & Research Institute
      • Tampa, Florida, Vereinigte Staaten, 33612
        • H. Lee Moffitt Cancer Center & Research Institute
    • Georgia
      • Atlanta, Georgia, Vereinigte Staaten, 30322
        • Emory University-Winship Cancer Institute
    • Maryland
      • Baltimore, Maryland, Vereinigte Staaten, 21201
        • University of Maryland
    • Massachusetts
      • Boston, Massachusetts, Vereinigte Staaten, 02215
        • Dana-Farber Cancer Center
    • Michigan
      • Ann Arbor, Michigan, Vereinigte Staaten, 48109
        • University of Michigan Comprehensive Cancer Center
    • Nebraska
      • Omaha, Nebraska, Vereinigte Staaten, 69198
        • University of Nebraska Medical Center
    • Ohio
      • Cincinnati, Ohio, Vereinigte Staaten, 45236
        • Oncology Hematology Care Clinical Trials LLC
    • Oklahoma
      • Oklahoma City, Oklahoma, Vereinigte Staaten, 73104
        • Stephenson Cancer Center
    • Tennessee
      • Nashville, Tennessee, Vereinigte Staaten, 37232
        • Vanderbilt University Medical Center
      • Nashville, Tennessee, Vereinigte Staaten, 37203
        • Tennessee Oncology
    • Texas
      • Austin, Texas, Vereinigte Staaten, 78705
        • Texas Oncology
      • Tyler, Texas, Vereinigte Staaten, 75702
        • Texas Oncology
    • Wisconsin
      • Milwaukee, Wisconsin, Vereinigte Staaten, 53226
        • Medical College of Wisconsin

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

18 Jahre und älter (Erwachsene, Älterer Erwachsener)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Alle

Beschreibung

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

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: Nicht randomisiert
  • Interventionsmodell: Einzelgruppenzuweisung
  • Maskierung: Keine (Offenes Etikett)

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Experimental: 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.
Arzneimittel: 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.
Experimental: 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.
Arzneimittel: 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.

Arzneimittel: Azacitidine
Azacitidine dose will be 75 mg/m^2. Azacitidine will be administered either sub-cutaneously (SC) or intravenously (IV).
Andere Namen:
  • Vidaza®
Experimental: 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.
Arzneimittel: 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.

Arzneimittel: I-DAC (Intermediate dose cytarabine)
Cytarabine dose will be 1 g/m^2. Cytarabine will be administered as an intravenous (IV) infusion.
Experimental: 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.
Arzneimittel: 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.

Arzneimittel: Ruxolitinib
Starting dose of ruxolitinib will be the dose the subject was on at study entry Ruxolitinib will be administered by mouth.
Experimental: 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.
Arzneimittel: 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.
Experimental: 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.
Arzneimittel: 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.
Experimental: 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.
Arzneimittel: 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.
Experimental: 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.
Arzneimittel: 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.
Experimental: 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.
Arzneimittel: 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.

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Determination of the Safety and Tolerability of INCB053914 as Measured by the Number of Participants With Adverse Events
Zeitfenster: 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)
Zeitfenster: 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
Zeitfenster: 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

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Evaluation of Phosphorylated BCL--2 Associated Death Promoter Protein (pBAD)
Zeitfenster: 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
Zeitfenster: Cycle 1 Day 5
Cycle 1 Day 5
Pharmacokinetics: AUCtau of Combination Treatment Group A INCB053914 50 mg + Cytarabine
Zeitfenster: Cycle 1 Day 5
Cycle 1 Day 5
Pharmacokinetics: Cl/F of Combination Treatment Group A INCB053914 50 mg + Cytarabine
Zeitfenster: Cycle 1 Day 5
Cycle 1 Day 5
Pharmacokinetics: Cmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine
Zeitfenster: Cycle 1 Day 5
Cycle 1 Day 5
Pharmacokinetics: Cmin of Combination Treatment Group A INCB053914 50 mg + Cytarabine
Zeitfenster: Cycle 1 Day 5
Cycle 1 Day 5
Pharmacokinetics: Tmax of Combination Group B INCB053914 80 mg + Azatcitidine
Zeitfenster: Cycle 1 Day 8
Cycle 1 Day 8
Pharmacokinetics: AUCtau of Combination Group B INCB053914 80 mg + Azatcitidine
Zeitfenster: Cycle 1 Day 8
Cycle 1 Day 8
Pharmacokinetics: Cl/F of Combination Group B INCB053914 80 mg + Azatcitidine
Zeitfenster: Cycle 1 Day 8
Cycle 1 Day 8
Pharmacokinetics: Cmax of Combination Group B INCB053914 80 mg + Azatcitidine
Zeitfenster: Cycle 1 Day 8
Cycle 1 Day 8
Pharmacokinetics: Cmin of Combination Group B INCB053914 80 mg + Azatcitidine
Zeitfenster: Cycle 1 Day 8
Cycle 1 Day 8
Pharmacokinetics: Tmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Zeitfenster: Regimen 2 Week 4
Regimen 2 Week 4
Pharmacokinetics: AUCtau of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Zeitfenster: Regimen 2 Week 4
Regimen 2 Week 4
Pharmacokinetics: Cl/F of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Zeitfenster: Regimen 2 Week 4
Regimen 2 Week 4
Pharmacokinetics: Cmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Zeitfenster: Regimen 2 Week 4
Regimen 2 Week 4
Pharmacokinetics: Cmin of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Zeitfenster: Regimen 2 Week 4
Regimen 2 Week 4
Pharmacokinetics: Tmax of INCB053914 Monotherapy
Zeitfenster: Cycle 1 Day 8
Cycle 1 Day 8
Pharmacokinetics: AUCtau of INCB053914 Monotherapy
Zeitfenster: Cycle 1 Day 8
Cycle 1 Day 8
Pharmacokinetics: CL/F of INCB053914 Monotherapy
Zeitfenster: Cycle 1 Day 8
Cycle 1 Day 8
Pharmacokinetics: Cmax of INCB053914 Monotherapy
Zeitfenster: Cycle 1 Day 8
Cycle 1 Day 8
Pharmacokinetics: Ctau of INCB053914 Monotherapy
Zeitfenster: Cycle 1 Day 8
Cycle 1 Day 8

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

Incyte Corporation

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn (Tatsächlich)

29. Dezember 2015

Primärer Abschluss (Tatsächlich)

11. August 2020

Studienabschluss (Tatsächlich)

11. August 2020

Studienanmeldedaten

Zuerst eingereicht

26. Oktober 2015

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

26. Oktober 2015

Zuerst gepostet (Schätzen)

27. Oktober 2015

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

8. Dezember 2021

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

9. November 2021

Zuletzt verifiziert

1. November 2021

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Schlüsselwörter

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • INCB 53914-101

Arzneimittel- und Geräteinformationen, Studienunterlagen

Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt

Nein

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