Study of INCB053914 in Subjects With Advanced Malignancies
9 de noviembre de 2021 actualizado por: 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).
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Intervencionista
Inscripción (Actual)
97
Fase
- Fase 2
- Fase 1
Acceso ampliado
Aprobado en venta al público.
Ver registro de acceso ampliado.
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Arizona
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Tucson, Arizona, Estados Unidos, 85719
- The University of Arizona Cancer Center
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California
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Sacramento, California, Estados Unidos, 95817
- UC Davis Comprehensive Cancer Center
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Santa Monica, California, Estados Unidos, 90095
- UCLA Medical Hematology & Oncology
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Connecticut
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New Haven, Connecticut, Estados Unidos, 06511
- Yale University
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Florida
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Jacksonville, Florida, Estados Unidos, 32224
- Mayo Clinic Florida
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Sarasota, Florida, Estados Unidos, 33916
- Florida Cancer Specialists & Research Institute
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Tampa, Florida, Estados Unidos, 33612
- H. Lee Moffitt Cancer Center & Research Institute
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Georgia
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Atlanta, Georgia, Estados Unidos, 30322
- Emory University-Winship Cancer Institute
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Maryland
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Baltimore, Maryland, Estados Unidos, 21201
- University of Maryland
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02215
- Dana-Farber Cancer Center
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Michigan
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Ann Arbor, Michigan, Estados Unidos, 48109
- University Of Michigan Comprehensive Cancer Center
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Nebraska
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Omaha, Nebraska, Estados Unidos, 69198
- University of Nebraska Medical Center
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Ohio
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Cincinnati, Ohio, Estados Unidos, 45236
- Oncology Hematology Care Clinical Trials LLC
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Oklahoma
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Oklahoma City, Oklahoma, Estados Unidos, 73104
- Stephenson Cancer Center
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Tennessee
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Nashville, Tennessee, Estados Unidos, 37232
- Vanderbilt University Medical Center
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Nashville, Tennessee, Estados Unidos, 37203
- Tennessee Oncology
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Texas
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Austin, Texas, Estados Unidos, 78705
- Texas Oncology
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Tyler, Texas, Estados Unidos, 75702
- Texas Oncology
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Wisconsin
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Milwaukee, Wisconsin, Estados Unidos, 53226
- Medical College of Wisconsin
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
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 de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: No aleatorizado
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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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.
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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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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.
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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).
Otros nombres:
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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.
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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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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.
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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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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.
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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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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.
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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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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.
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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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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.
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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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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.
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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. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Determination of the Safety and Tolerability of INCB053914 as Measured by the Number of Participants With Adverse Events
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 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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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Evaluation of Phosphorylated BCL--2 Associated Death Promoter Protein (pBAD)
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: Regimen 2 Week 4
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Regimen 2 Week 4
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Pharmacokinetics: Tmax of INCB053914 Monotherapy
Periodo de tiempo: Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: AUCtau of INCB053914 Monotherapy
Periodo de tiempo: Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: CL/F of INCB053914 Monotherapy
Periodo de tiempo: Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: Cmax of INCB053914 Monotherapy
Periodo de tiempo: Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: Ctau of INCB053914 Monotherapy
Periodo de tiempo: Cycle 1 Day 8
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Cycle 1 Day 8
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
29 de diciembre de 2015
Finalización primaria (Actual)
11 de agosto de 2020
Finalización del estudio (Actual)
11 de agosto de 2020
Fechas de registro del estudio
Enviado por primera vez
26 de octubre de 2015
Primero enviado que cumplió con los criterios de control de calidad
26 de octubre de 2015
Publicado por primera vez (Estimar)
27 de octubre de 2015
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
8 de diciembre de 2021
Última actualización enviada que cumplió con los criterios de control de calidad
9 de noviembre de 2021
Última verificación
1 de noviembre de 2021
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Neoplasias
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Agentes antiinfecciosos
- Agentes Antivirales
- Inhibidores de enzimas
- Antimetabolitos, Antineoplásicos
- Antimetabolitos
- Agentes antineoplásicos
- Agentes inmunosupresores
- Factores inmunológicos
- Azacitidina
- Citarabina
Otros números de identificación del estudio
- INCB 53914-101
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .