- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT01164163
INCB18424 in Treating Young Patients With Relapsed or Refractory Solid Tumor, Leukemia, or Myeloproliferative Disease
A Phase I Study of JAK Inhibition (INCB018424) in Children With Relapsed or Refractory Solid Tumors, Leukemias, and Myeloproliferative Neoplasms
RATIONALE: INCB18424 (Ruxolitinib) may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase 1 clinical trial is studying the side effects and best dose of INCB18424 in treating young patients with relapsed or refractory solid tumor, leukemia, or myeloproliferative disease.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
OBJECTIVES:
Primary
- To estimate the maximum-tolerated dose and/or recommended phase II dose of oral JAK inhibitor INCB18424 administered continuously, twice daily to pediatric patients with relapsed or refractory solid tumors.
- To define and describe the toxicities of this treatment administered on this schedule in pediatric patients with relapsed or refractory solid tumors, leukemias, or myeloproliferative neoplasms (MPNs).
- To characterize the pharmacokinetics of this treatment in pediatric patients with relapsed or refractory solid tumors, leukemias, or MPNs.
Secondary
- To preliminarily define the antitumor activity of this treatment within the confines of a phase I study.
- To assess the biologic activity of oral JAK inhibitor INCB18424 upon JAK-STAT signaling in pediatric patients with relapsed or refractory solid tumors, leukemias, or MPNs.
- To assess the cytotoxicity and biologic activity of oral JAK inhibitor INCB18424 upon phosphosignaling and mutation burden in pediatric patients whose leukemias or MPNs have known CRLF2 and/or JAK mutations.
OUTLINE: This is a multicenter, dose-escalation study.
Patients receive oral JAK inhibitor INCB18424 twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients with relapsed or refractory leukemia may receive intrathecal chemotherapy in course 2 and subsequent courses at the discretion of the treating physician.
Plasma, bone marrow, and blood samples may be collected at baseline, during course 1, and before subsequent courses for pharmacokinetic analysis and correlative biology studies.
After completion of study treatment, patients are followed up for 30 days.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
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Alabama
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Birmingham, Alabama, Estados Unidos, 35294
- UAB Comprehensive Cancer Center
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California
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Orange, California, Estados Unidos, 92868
- Children's Hospital of Orange County
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San Francisco, California, Estados Unidos, 94115
- UCSF Helen Diller Family Comprehensive Cancer Center
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Colorado
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Aurora, Colorado, Estados Unidos, 80045
- Children's Hospital Colorado Center for Cancer and Blood Disorders
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District of Columbia
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Washington, District of Columbia, Estados Unidos, 20010-2970
- Children's National Medical Center
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Georgia
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Atlanta, Georgia, Estados Unidos, 30322
- AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
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Illinois
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Chicago, Illinois, Estados Unidos, 60611
- Children's Memorial Hospital - Chicago
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Indiana
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Indianapolis, Indiana, Estados Unidos, 46202
- Riley's Children Cancer Center at Riley Hospital for Children
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Maryland
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Baltimore, Maryland, Estados Unidos, 21231-2410
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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Bethesda, Maryland, Estados Unidos, 20892-1182
- Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02115
- Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
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Michigan
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Ann Arbor, Michigan, Estados Unidos, 48109-0286
- C.S. Mott Children's Hospital at University of Michigan Medical Center
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Minnesota
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Minneapolis, Minnesota, Estados Unidos, 55455
- Masonic Cancer Center at University of Minnesota
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Missouri
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St. Louis, Missouri, Estados Unidos, 63110
- Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
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New York
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New York, New York, Estados Unidos, 10032
- Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
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Ohio
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Cincinnati, Ohio, Estados Unidos, 45229-3039
- Cincinnati Children's Hospital Medical Center
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Oregon
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Portland, Oregon, Estados Unidos, 97239-3098
- Knight Cancer Institute At Oregon Health and Science University
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Pennsylvania
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Philadelphia, Pennsylvania, Estados Unidos, 19104
- Children's Hospital of Philadelphia
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Pittsburgh, Pennsylvania, Estados Unidos, 15213
- Children's Hospital of Pittsburgh of UPMC
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Tennessee
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Memphis, Tennessee, Estados Unidos, 38105
- St. Jude Children's Research Hospital
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Texas
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Dallas, Texas, Estados Unidos, 75390
- Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
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Houston, Texas, Estados Unidos, 77030-2399
- Baylor University Medical Center - Houston
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Washington
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Seattle, Washington, Estados Unidos, 98105
- Children's Hospital and Regional Medical Center - Seattle
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Wisconsin
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Milwaukee, Wisconsin, Estados Unidos, 53226
- Midwest Children's Cancer Center at Children's Hospital of Wisconsin
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
DISEASE CHARACTERISTICS:
Histologically confirmed diagnosis of one of the following:
- Relapsed or refractory extracranial solid tumor
Relapsed or refractory leukemia
- At least 25% blasts in the bone marrow (M3) with the exception of patients with acute myeloid leukemia (AML), who must have > 20% blasts in the bone marrow
Relapsed or refractory myeloproliferative neoplasm (MPN)
- At original diagnosis or relapse
- Current diagnostic criteria for MPNs include polycythemia vera, essential thrombocythemia, juvenile myelomonocytic leukemia, myelofibrosis, and atypical chronic myeloid leukemia
Relapsed or refractory leukemia or MPN that have confirmed JAK mutations and/or positive TSLPR surface staining
- Testing for JAK mutations and/or confirmed positive flow cytometry surface staining for the thymic stromal lymphopoietin receptor (TSLPR; encoded by CRLF2); eligibility for part C will be contingent upon patients demonstrating overexpression of CRLF2 by flow cytometric methods measured at either JHU or U. Washington flow laboratories (therefore, pre-enrollment samples need to be sent to one of these laboratories after discussion with Dr. Loh) or if the patient has a CLIA lab documented alteration in JAK1 or JAK2, SH2B3, IL7RA, or another gene that would predict sensitivity to JAK inhibition.
- Measurable or evaluable disease (for patients with solid tumors)
- Current disease state is one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
- No known active CNS involvement (radiographic or cytologic)
PATIENT CHARACTERISTICS:
Karnofsky performance status (PS) 50-100% (for patients > 16 years old) or Lansky PS 50-100% (for patients ≤ 16 years old)
- Patients who are unable to walk because of paralysis, but who can actively sit up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance status
Patients with solid tumors* must meet the following criteria:
- Peripheral ANC ≥ 1,000/mm^3
- Platelet count ≥ 100,000/mm^3 (transfusion-independent, defined as > 7 days since prior platelet transfusions)
Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusions)
- Not refractory to to red cell or platelet transfusion
- ALT ≤ 110 U/L NOTE: *Patients with solid tumors and known bone marrow metastatic disease are eligible for study, but not evaluable for hematologic toxicity. These patients must not be known to be refractory to RBC or platelet transfusions.
Patients with leukemia or MPNs must meet the following criteria:
- Platelet count ≥ 20,000/mm^3 (may receive platelet infusions)
- Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusions)
- ALT ≤ 225 U/L
Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR serum creatinine based on age/gender as follows:
- ≤ 0.6 mg/dL (for patients 1 to < 2 years old)
- ≤ 0.8 mg/dL (for patients 2 to < 6 years old)
- ≤ 1 mg/dL (for patients 6 to < 10 years old)
- ≤ 1.2 mg/dL (for patients 10 to < 13 years old)
- ≤ 1.4 mg/dL (for female patients ≥ 13 years old)
- ≤ 1.5 mg/dL (for male patients 13 to < 16 years old)
- ≤ 1.7 mg/dL (for male patients ≥ 16 years old)
- Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 times upper limit of normal for age
- Serum albumin ≥ 2 g/dL
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
Able to swallow crushed or whole tablets
- Nasogastric or G tube administration is not allowed
- Body surface area ≥ 0.65 m^2 (for patients at dose level -1, 1, and 2)
- No uncontrolled infection, including patients with known active HIV or chronic hepatitis
- No patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study
PRIOR CONCURRENT THERAPY:
- Fully recovered from the acute toxic effects of all prior anticancer therapy
- At least 2 weeks since prior local palliative radiotherapy (small port)
- At least 6 months since prior total-body irradiation (TBI), craniospinal radiotherapy, or radiotherapy to ≥ 50% of the pelvis (for patients with solid tumors)
- At least 3 months since prior TBI, craniospinal radiotherapy, or radiotherapy to ≥ 50% of the pelvis (for patients with leukemia)
- At least 3 months since prior stem cell transplantation or rescue without TBI and no evidence of active graft-vs-host disease
- At least 6 weeks since other substantial bone marrow radiation
- At least 3 weeks since prior myelosuppressive therapy (6 weeks for nitrosourea) (for patients with solid tumors)
At least 2 weeks since prior cytoxic chemotherapy (for patients with leukemia or MPNs)
- Hydroxyurea may be initiated and continued for up to 24 hours before the start of study treatment
- Intrathecal cytarabine (Ara-C) is not myelosuppressive chemotherapy
- Patients with leukemia are permitted to receive intrathecal chemotherapy, including methotrexate or cytarabine, only if this is given at the time of diagnostic lumbar puncture at least 24 hours prior to the start of INCB018424
At least 2 weeks since prior long-acting hematopoietic growth factor (e.g., Neulasta) or 1 week for a short-acting growth factor
- For agents that have known adverse events occurring beyond 1 week, this period must be extended beyond the time during which adverse events are known to occur (as discussed with the study chair)
At least 1 week since prior therapy with a biologic (antineoplastic) agent
- For agents that have known adverse events occurring beyond 1 week, this period must be extended beyond the time during which adverse events are known to occur (as discussed with the study chair)
- At least 3 half-lives of antibody since prior monoclonal antibody
- No other concurrent investigational drugs
- No other concurrent anticancer agents, including chemotherapy, radiotherapy, immunotherapy, or biologic therapy
- No concurrent systemic steroids (i.e., prednisone > 10 mg)
- No concurrent aspirin > 150 mg/day
- No concurrent medications for myelofibrosis (e.g., hydroxyurea, interferon, thalidomide, busulfan, lenalidomide, or anagrelide)
- No concurrent cyclosporine, tacrolimus, or other agents to prevent graft-vs-host disease after bone marrow transplant or organ rejection after transplant
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
---|---|
Experimental: Treatment (Ruxolitinib)
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
---|---|
Maximum-tolerated dose and/or recommended phase II dose
Periodo de tiempo: 28 days
|
28 days
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Toxicity
Periodo de tiempo: 30 days post treatment
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30 days post treatment
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Pharmacokinetics
Periodo de tiempo: Up to 28 days
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Up to 28 days
|
Medidas de resultado secundarias
Medida de resultado |
Periodo de tiempo |
---|---|
Antitumor activity
Periodo de tiempo: Up to 30 days post treatment
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Up to 30 days post treatment
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Toxicity and biologic activity
Periodo de tiempo: Day 1 and Day 15
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Day 1 and Day 15
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
- tumor sólido infantil no especificado, protocolo específico
- mielofibrosis primaria
- leucemia mielomonocítica crónica
- síndromes mielodisplásicos previamente tratados
- leucemia mielomonocítica juvenil
- síndromes mielodisplásicos infantiles
- leucemia mielógena crónica recidivante
- leucemia linfocítica crónica refractaria
- policitemia vera
- trombocitemia esencial
- leucemia linfoblástica aguda infantil recurrente
- leucemia mieloide aguda infantil recurrente
- neoplasia mielodisplásica/mieloproliferativa, inclasificable
- leucemia mieloide crónica atípica, BCR-ABL1 negativo
- leucemia promielocítica aguda infantil (M3)
- leucemia mieloide aguda/trastorno mieloproliferativo transitorio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- ADVL1011
- COG-ADVL1011 (Otro identificador: Children's Oncology Group)
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. .
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