Study of INCB053914 in Subjects With Advanced Malignancies
9 listopada 2021 zaktualizowane przez: 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).
Przegląd badań
Status
Zakończony
Warunki
Interwencja / Leczenie
Typ studiów
Interwencyjne
Zapisy (Rzeczywisty)
97
Faza
- Faza 2
- Faza 1
Rozszerzony dostęp
Zatwierdzony do sprzedaży publicznej.
Zobacz rozwinięty rekord dostępu.
Kontakty i lokalizacje
Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.
Lokalizacje studiów
-
-
Arizona
-
Tucson, Arizona, Stany Zjednoczone, 85719
- The University of Arizona Cancer Center
-
-
California
-
Sacramento, California, Stany Zjednoczone, 95817
- UC Davis Comprehensive Cancer Center
-
Santa Monica, California, Stany Zjednoczone, 90095
- UCLA Medical Hematology & Oncology
-
-
Connecticut
-
New Haven, Connecticut, Stany Zjednoczone, 06511
- Yale University
-
-
Florida
-
Jacksonville, Florida, Stany Zjednoczone, 32224
- Mayo Clinic Florida
-
Sarasota, Florida, Stany Zjednoczone, 33916
- Florida Cancer Specialists & Research Institute
-
Tampa, Florida, Stany Zjednoczone, 33612
- H. Lee Moffitt Cancer Center & Research Institute
-
-
Georgia
-
Atlanta, Georgia, Stany Zjednoczone, 30322
- Emory University-Winship Cancer Institute
-
-
Maryland
-
Baltimore, Maryland, Stany Zjednoczone, 21201
- University of Maryland
-
-
Massachusetts
-
Boston, Massachusetts, Stany Zjednoczone, 02215
- Dana-Farber Cancer Center
-
-
Michigan
-
Ann Arbor, Michigan, Stany Zjednoczone, 48109
- University Of Michigan Comprehensive Cancer Center
-
-
Nebraska
-
Omaha, Nebraska, Stany Zjednoczone, 69198
- University of Nebraska Medical Center
-
-
Ohio
-
Cincinnati, Ohio, Stany Zjednoczone, 45236
- Oncology Hematology Care Clinical Trials LLC
-
-
Oklahoma
-
Oklahoma City, Oklahoma, Stany Zjednoczone, 73104
- Stephenson Cancer Center
-
-
Tennessee
-
Nashville, Tennessee, Stany Zjednoczone, 37232
- Vanderbilt University Medical Center
-
Nashville, Tennessee, Stany Zjednoczone, 37203
- Tennessee Oncology
-
-
Texas
-
Austin, Texas, Stany Zjednoczone, 78705
- Texas Oncology
-
Tyler, Texas, Stany Zjednoczone, 75702
- Texas Oncology
-
-
Wisconsin
-
Milwaukee, Wisconsin, Stany Zjednoczone, 53226
- Medical College of Wisconsin
-
-
Kryteria uczestnictwa
Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.
Kryteria kwalifikacji
Wiek uprawniający do nauki
18 lat i starsze (Dorosły, Starszy dorosły)
Akceptuje zdrowych ochotników
Nie
Płeć kwalifikująca się do nauki
Wszystko
Opis
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
Plan studiów
Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.
Jak projektuje się badanie?
Szczegóły projektu
- Główny cel: Leczenie
- Przydział: Nielosowe
- Model interwencyjny: Zadanie dla jednej grupy
- Maskowanie: Brak (otwarta etykieta)
Broń i interwencje
Grupa uczestników / Arm |
Interwencja / Leczenie |
|---|---|
|
Eksperymentalny: 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. |
|
Eksperymentalny: 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).
Inne nazwy:
|
|
Eksperymentalny: 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.
|
|
Eksperymentalny: 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.
|
|
Eksperymentalny: 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. |
|
Eksperymentalny: 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. |
|
Eksperymentalny: 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. |
|
Eksperymentalny: 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. |
|
Eksperymentalny: 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. |
Co mierzy badanie?
Podstawowe miary wyniku
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
|
Determination of the Safety and Tolerability of INCB053914 as Measured by the Number of Participants With Adverse Events
Ramy czasowe: 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)
Ramy czasowe: 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
Ramy czasowe: 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
|
Miary wyników drugorzędnych
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
|
Evaluation of Phosphorylated BCL--2 Associated Death Promoter Protein (pBAD)
Ramy czasowe: 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
Ramy czasowe: Cycle 1 Day 5
|
Cycle 1 Day 5
|
|
|
Pharmacokinetics: AUCtau of Combination Treatment Group A INCB053914 50 mg + Cytarabine
Ramy czasowe: Cycle 1 Day 5
|
Cycle 1 Day 5
|
|
|
Pharmacokinetics: Cl/F of Combination Treatment Group A INCB053914 50 mg + Cytarabine
Ramy czasowe: Cycle 1 Day 5
|
Cycle 1 Day 5
|
|
|
Pharmacokinetics: Cmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine
Ramy czasowe: Cycle 1 Day 5
|
Cycle 1 Day 5
|
|
|
Pharmacokinetics: Cmin of Combination Treatment Group A INCB053914 50 mg + Cytarabine
Ramy czasowe: Cycle 1 Day 5
|
Cycle 1 Day 5
|
|
|
Pharmacokinetics: Tmax of Combination Group B INCB053914 80 mg + Azatcitidine
Ramy czasowe: Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: AUCtau of Combination Group B INCB053914 80 mg + Azatcitidine
Ramy czasowe: Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: Cl/F of Combination Group B INCB053914 80 mg + Azatcitidine
Ramy czasowe: Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: Cmax of Combination Group B INCB053914 80 mg + Azatcitidine
Ramy czasowe: Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: Cmin of Combination Group B INCB053914 80 mg + Azatcitidine
Ramy czasowe: Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: Tmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Ramy czasowe: Regimen 2 Week 4
|
Regimen 2 Week 4
|
|
|
Pharmacokinetics: AUCtau of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Ramy czasowe: Regimen 2 Week 4
|
Regimen 2 Week 4
|
|
|
Pharmacokinetics: Cl/F of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Ramy czasowe: Regimen 2 Week 4
|
Regimen 2 Week 4
|
|
|
Pharmacokinetics: Cmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Ramy czasowe: Regimen 2 Week 4
|
Regimen 2 Week 4
|
|
|
Pharmacokinetics: Cmin of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Ramy czasowe: Regimen 2 Week 4
|
Regimen 2 Week 4
|
|
|
Pharmacokinetics: Tmax of INCB053914 Monotherapy
Ramy czasowe: Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: AUCtau of INCB053914 Monotherapy
Ramy czasowe: Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: CL/F of INCB053914 Monotherapy
Ramy czasowe: Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: Cmax of INCB053914 Monotherapy
Ramy czasowe: Cycle 1 Day 8
|
Cycle 1 Day 8
|
|
|
Pharmacokinetics: Ctau of INCB053914 Monotherapy
Ramy czasowe: Cycle 1 Day 8
|
Cycle 1 Day 8
|
Współpracownicy i badacze
Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.
Sponsor
Daty zapisu na studia
Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.
Główne daty studiów
Rozpoczęcie studiów (Rzeczywisty)
29 grudnia 2015
Zakończenie podstawowe (Rzeczywisty)
11 sierpnia 2020
Ukończenie studiów (Rzeczywisty)
11 sierpnia 2020
Daty rejestracji na studia
Pierwszy przesłany
26 października 2015
Pierwszy przesłany, który spełnia kryteria kontroli jakości
26 października 2015
Pierwszy wysłany (Oszacować)
27 października 2015
Aktualizacje rekordów badań
Ostatnia wysłana aktualizacja (Rzeczywisty)
8 grudnia 2021
Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości
9 listopada 2021
Ostatnia weryfikacja
1 listopada 2021
Więcej informacji
Terminy związane z tym badaniem
Słowa kluczowe
Dodatkowe istotne warunki MeSH
- Nowotwory
- Fizjologiczne skutki leków
- Molekularne mechanizmy działania farmakologicznego
- Środki przeciwinfekcyjne
- Środki przeciwwirusowe
- Inhibitory enzymów
- Antymetabolity, przeciwnowotworowe
- Antymetabolity
- Środki przeciwnowotworowe
- Środki immunosupresyjne
- Czynniki immunologiczne
- Azacytydyna
- Cytarabina
Inne numery identyfikacyjne badania
- INCB 53914-101
Informacje o lekach i urządzeniach, dokumenty badawcze
Bada produkt urządzenia regulowany przez amerykańską FDA
Nie
Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .