Study of INCB053914 in Subjects With Advanced Malignancies
9 november 2021 bijgewerkt door: 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).
Studie Overzicht
Toestand
Beëindigd
Conditie
Studietype
Ingrijpend
Inschrijving (Werkelijk)
97
Fase
- Fase 2
- Fase 1
Uitgebreide toegang
Goedgekeurd te koop aan het publiek.
Zie uitgebreid toegangsrecord.
Contacten en locaties
In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.
Studie Locaties
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Arizona
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Tucson, Arizona, Verenigde Staten, 85719
- The University of Arizona Cancer Center
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California
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Sacramento, California, Verenigde Staten, 95817
- UC Davis Comprehensive Cancer Center
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Santa Monica, California, Verenigde Staten, 90095
- UCLA Medical Hematology & Oncology
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Connecticut
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New Haven, Connecticut, Verenigde Staten, 06511
- Yale University
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Florida
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Jacksonville, Florida, Verenigde Staten, 32224
- Mayo Clinic Florida
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Sarasota, Florida, Verenigde Staten, 33916
- Florida Cancer Specialists & Research Institute
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Tampa, Florida, Verenigde Staten, 33612
- H. Lee Moffitt Cancer Center & Research Institute
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Georgia
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Atlanta, Georgia, Verenigde Staten, 30322
- Emory University-Winship Cancer Institute
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Maryland
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Baltimore, Maryland, Verenigde Staten, 21201
- University of Maryland
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Massachusetts
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Boston, Massachusetts, Verenigde Staten, 02215
- Dana-Farber Cancer Center
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Michigan
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Ann Arbor, Michigan, Verenigde Staten, 48109
- University Of Michigan Comprehensive Cancer Center
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Nebraska
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Omaha, Nebraska, Verenigde Staten, 69198
- University of Nebraska Medical Center
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Ohio
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Cincinnati, Ohio, Verenigde Staten, 45236
- Oncology Hematology Care Clinical Trials LLC
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Oklahoma
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Oklahoma City, Oklahoma, Verenigde Staten, 73104
- Stephenson Cancer Center
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Tennessee
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Nashville, Tennessee, Verenigde Staten, 37232
- Vanderbilt University Medical Center
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Nashville, Tennessee, Verenigde Staten, 37203
- Tennessee Oncology
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Texas
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Austin, Texas, Verenigde Staten, 78705
- Texas Oncology
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Tyler, Texas, Verenigde Staten, 75702
- Texas Oncology
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Wisconsin
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Milwaukee, Wisconsin, Verenigde Staten, 53226
- Medical College of Wisconsin
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Deelname Criteria
Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
18 jaar en ouder (Volwassen, Oudere volwassene)
Accepteert gezonde vrijwilligers
Nee
Geslachten die in aanmerking komen voor studie
Allemaal
Beschrijving
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
Studie plan
Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Niet-gerandomiseerd
- Interventioneel model: Opdracht voor een enkele groep
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
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Experimenteel: 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.
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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. |
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Experimenteel: 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.
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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).
Andere namen:
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Experimenteel: 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.
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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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Experimenteel: 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.
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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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Experimenteel: 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.
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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. |
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Experimenteel: 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.
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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. |
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Experimenteel: 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.
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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. |
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Experimenteel: 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.
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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. |
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Experimenteel: 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.
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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. |
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Determination of the Safety and Tolerability of INCB053914 as Measured by the Number of Participants With Adverse Events
Tijdsspanne: 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)
Tijdsspanne: 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
Tijdsspanne: 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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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Evaluation of Phosphorylated BCL--2 Associated Death Promoter Protein (pBAD)
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: Regimen 2 Week 4
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Regimen 2 Week 4
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Pharmacokinetics: Cl/F of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Tijdsspanne: Regimen 2 Week 4
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Regimen 2 Week 4
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Pharmacokinetics: Cmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Tijdsspanne: Regimen 2 Week 4
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Regimen 2 Week 4
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Pharmacokinetics: Cmin of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Tijdsspanne: Regimen 2 Week 4
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Regimen 2 Week 4
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Pharmacokinetics: Tmax of INCB053914 Monotherapy
Tijdsspanne: Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: AUCtau of INCB053914 Monotherapy
Tijdsspanne: Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: CL/F of INCB053914 Monotherapy
Tijdsspanne: Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: Cmax of INCB053914 Monotherapy
Tijdsspanne: Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: Ctau of INCB053914 Monotherapy
Tijdsspanne: Cycle 1 Day 8
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Cycle 1 Day 8
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Medewerkers en onderzoekers
Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.
Sponsor
Studie record data
Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.
Bestudeer belangrijke data
Studie start (Werkelijk)
29 december 2015
Primaire voltooiing (Werkelijk)
11 augustus 2020
Studie voltooiing (Werkelijk)
11 augustus 2020
Studieregistratiedata
Eerst ingediend
26 oktober 2015
Eerst ingediend dat voldeed aan de QC-criteria
26 oktober 2015
Eerst geplaatst (Schatting)
27 oktober 2015
Updates van studierecords
Laatste update geplaatst (Werkelijk)
8 december 2021
Laatste update ingediend die voldeed aan QC-criteria
9 november 2021
Laatst geverifieerd
1 november 2021
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
- Neoplasmata
- Fysiologische effecten van medicijnen
- Moleculaire mechanismen van farmacologische werking
- Anti-infectieuze middelen
- Antivirale middelen
- Enzymremmers
- Antimetabolieten, antineoplastische
- Antimetabolieten
- Antineoplastische middelen
- Immunosuppressieve middelen
- Immunologische factoren
- Azacitidine
- Cytarabine
Andere studie-ID-nummers
- INCB 53914-101
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
Nee
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .