Study of INCB053914 in Subjects With Advanced Malignancies
9 november 2021 uppdaterad av: 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).
Studieöversikt
Status
Avslutad
Betingelser
Intervention / Behandling
Studietyp
Interventionell
Inskrivning (Faktisk)
97
Fas
- Fas 2
- Fas 1
Utökad åtkomst
Godkänd till försäljning till allmänheten.
Se utökad åtkomstpost.
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
-
-
Arizona
-
Tucson, Arizona, Förenta staterna, 85719
- The University of Arizona Cancer Center
-
-
California
-
Sacramento, California, Förenta staterna, 95817
- UC Davis Comprehensive Cancer Center
-
Santa Monica, California, Förenta staterna, 90095
- UCLA Medical Hematology & Oncology
-
-
Connecticut
-
New Haven, Connecticut, Förenta staterna, 06511
- Yale University
-
-
Florida
-
Jacksonville, Florida, Förenta staterna, 32224
- Mayo Clinic Florida
-
Sarasota, Florida, Förenta staterna, 33916
- Florida Cancer Specialists & Research Institute
-
Tampa, Florida, Förenta staterna, 33612
- H. Lee Moffitt Cancer Center & Research Institute
-
-
Georgia
-
Atlanta, Georgia, Förenta staterna, 30322
- Emory University-Winship Cancer Institute
-
-
Maryland
-
Baltimore, Maryland, Förenta staterna, 21201
- University of Maryland
-
-
Massachusetts
-
Boston, Massachusetts, Förenta staterna, 02215
- Dana-Farber Cancer Center
-
-
Michigan
-
Ann Arbor, Michigan, Förenta staterna, 48109
- University Of Michigan Comprehensive Cancer Center
-
-
Nebraska
-
Omaha, Nebraska, Förenta staterna, 69198
- University of Nebraska Medical Center
-
-
Ohio
-
Cincinnati, Ohio, Förenta staterna, 45236
- Oncology Hematology Care Clinical Trials LLC
-
-
Oklahoma
-
Oklahoma City, Oklahoma, Förenta staterna, 73104
- Stephenson Cancer Center
-
-
Tennessee
-
Nashville, Tennessee, Förenta staterna, 37232
- Vanderbilt University Medical Center
-
Nashville, Tennessee, Förenta staterna, 37203
- Tennessee Oncology
-
-
Texas
-
Austin, Texas, Förenta staterna, 78705
- Texas Oncology
-
Tyler, Texas, Förenta staterna, 75702
- Texas Oncology
-
-
Wisconsin
-
Milwaukee, Wisconsin, Förenta staterna, 53226
- Medical College of Wisconsin
-
-
Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
18 år och äldre (Vuxen, Äldre vuxen)
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Allt
Beskrivning
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
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Icke-randomiserad
- Interventionsmodell: Enskild gruppuppgift
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
|
Experimentell: 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. |
|
Experimentell: 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).
Andra namn:
|
|
Experimentell: 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.
|
|
Experimentell: 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.
|
|
Experimentell: 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. |
|
Experimentell: 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. |
|
Experimentell: 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. |
|
Experimentell: 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. |
|
Experimentell: 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. |
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Determination of the Safety and Tolerability of INCB053914 as Measured by the Number of Participants With Adverse Events
Tidsram: 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)
Tidsram: 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
Tidsram: 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
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Evaluation of Phosphorylated BCL--2 Associated Death Promoter Protein (pBAD)
Tidsram: 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
Tidsram: Cycle 1 Day 5
|
Cycle 1 Day 5
|
|
|
Pharmacokinetics: AUCtau of Combination Treatment Group A INCB053914 50 mg + Cytarabine
Tidsram: Cycle 1 Day 5
|
Cycle 1 Day 5
|
|
|
Pharmacokinetics: Cl/F of Combination Treatment Group A INCB053914 50 mg + Cytarabine
Tidsram: Cycle 1 Day 5
|
Cycle 1 Day 5
|
|
|
Pharmacokinetics: Cmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine
Tidsram: Cycle 1 Day 5
|
Cycle 1 Day 5
|
|
|
Pharmacokinetics: Cmin of Combination Treatment Group A INCB053914 50 mg + Cytarabine
Tidsram: Cycle 1 Day 5
|
Cycle 1 Day 5
|
|
|
Pharmacokinetics: Tmax of Combination Group B INCB053914 80 mg + Azatcitidine
Tidsram: Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: AUCtau of Combination Group B INCB053914 80 mg + Azatcitidine
Tidsram: Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: Cl/F of Combination Group B INCB053914 80 mg + Azatcitidine
Tidsram: Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: Cmax of Combination Group B INCB053914 80 mg + Azatcitidine
Tidsram: Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: Cmin of Combination Group B INCB053914 80 mg + Azatcitidine
Tidsram: Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: Tmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Tidsram: Regimen 2 Week 4
|
Regimen 2 Week 4
|
|
|
Pharmacokinetics: AUCtau of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Tidsram: Regimen 2 Week 4
|
Regimen 2 Week 4
|
|
|
Pharmacokinetics: Cl/F of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Tidsram: Regimen 2 Week 4
|
Regimen 2 Week 4
|
|
|
Pharmacokinetics: Cmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Tidsram: Regimen 2 Week 4
|
Regimen 2 Week 4
|
|
|
Pharmacokinetics: Cmin of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Tidsram: Regimen 2 Week 4
|
Regimen 2 Week 4
|
|
|
Pharmacokinetics: Tmax of INCB053914 Monotherapy
Tidsram: Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: AUCtau of INCB053914 Monotherapy
Tidsram: Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: CL/F of INCB053914 Monotherapy
Tidsram: Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: Cmax of INCB053914 Monotherapy
Tidsram: Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: Ctau of INCB053914 Monotherapy
Tidsram: Cycle 1 Day 8
|
Cycle 1 Day 8
|
Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Sponsor
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart (Faktisk)
29 december 2015
Primärt slutförande (Faktisk)
11 augusti 2020
Avslutad studie (Faktisk)
11 augusti 2020
Studieregistreringsdatum
Först inskickad
26 oktober 2015
Först inskickad som uppfyllde QC-kriterierna
26 oktober 2015
Första postat (Uppskatta)
27 oktober 2015
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
8 december 2021
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
9 november 2021
Senast verifierad
1 november 2021
Mer information
Termer relaterade till denna studie
Nyckelord
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- INCB 53914-101
Läkemedels- och apparatinformation, studiedokument
Studerar en amerikansk FDA-reglerad produktprodukt
Nej
Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .