- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT00058240
Flavopiridol in Treating Patients With Previously Treated Chronic Lymphocytic Leukemia or Lymphocytic Lymphoma
A Dose-Escalation Study of Flavopiridol (NSC 649890) Administered as a 30 Minute Loading Dose Followed by a 4-Hour Infusion in Patients With Previously Treated B-Cell Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
PRIMARY OBJECTIVES:
I. To determine the toxicity profile, dose-limiting toxicity, and maximum tolerated dose of flavopiridol administered as a 30 minute loading dose followed by a 4-hour infusion once weekly for 4 consecutive weeks every 6 weeks.
II. To determine the safety and feasibility of performing dose escalation to 80 mg/m2 (30 mg/m2 30-minute IV bolus followed by 50 mg/m2 4-hour IV infusion) beginning dose 2 in patients who do not experience severe tumor lysis requiring hemodialysis during dose 1.
III. To determine the pharmacokinetics and cellular pharmacodynamics of flavopiridol administered in this schedule.
SECONDARY OBJECTIVES:
I. To determine the complete response (CR) and overall response rate (CR + PR) of flavopiridol in patients with previously-treated CLL administered as a 30 minute loading dose followed by a 4 hour infusion once weekly for 4 consecutive weeks every 6 weeks.
OUTLINE: This is a dose-escalation study.
Patients receive a loading dose of flavopiridol IV over 30 minutes followed by a 4-hour infusion on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in the absence of unacceptable toxicity or disease progression.
Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. After the MTD is determined, 12 additional patients are accrued and treated as above at the recommended phase II dose.
After completion of study treatment, patients are followed at 2 months and then every 3 months for 2 years.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
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Ohio
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Columbus, Ohio, Estados Unidos, 43210
- Ohio State University Medical Center
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
Diagnosis of B-cell chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma, including Waldenstrom's macroglobulinemia, as indicated by the following:
- Massive or progressive splenomegaly and/or lymphadenopathy
- Anemia (hemoglobin less than 11 g/dL) or thrombocytopenia (platelet count less than 100,000/mm^3)
- Weight loss of more than 10% within the past 6 months
- Grade 2 or 3 fatigue
- Fevers greater than 100.5º C or night sweats for more than 2 weeks with no evidence of infection
- Progressive lymphocytosis with an increase of more than 50% over a 2-month period or anticipated doubling time of less than 6 months
- Received at least 1 prior therapy for CLL
- Performance status - ECOG (Eastern Cooperative Oncology Group) 0-2
- See Disease Characteristics
- WBC (white blood count) less than 200,000/mm^3
- Bilirubin no greater than 1.5 times normal (unless due to Gilbert's disease or any of the conditions stated below)*
- AST (aspartate aminotransferase) no greater than 2 times normal*
- Creatinine no greater than 2.0 mg/dL
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No other malignancy that would limit survival to less than 2 years
- No history of inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis) unless inactive for more than 2 years
- No psychiatric condition that would preclude compliance with treatment or giving informed consent
- No other concurrent chemotherapy
- No concurrent chronic corticosteroids
- No concurrent hormonal therapy except steroids for new adrenal failure or hormonal agents for nondisease-related conditions (e.g., insulin for diabetes)
- No concurrent dexamethasone or other corticosteroid-based antiemetics
- No concurrent radiotherapy
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 |
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Experimental: Arm I
Patients receive a loading dose of flavopiridol IV over 30 minutes followed by a 4-hour infusion on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in the absence of unacceptable toxicity or disease progression.
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Dado IV
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Number of Patients With Dose Limiting Toxicities (DLTs)
Periodo de tiempo: up to 7 weeks
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DLTs were defined as non-hematologic toxicity of grade 3 or greater severity (excluding transient liver function abnormalities, transient electrolyte abnormalities that are not life threatening, fatigue, or diarrhea that resolve within 4 days), or in some case grade 2 toxicity (i.e.
irreversible renal, chronic pulmonary, neurologic, or cardiac toxicity).
Hematologic toxicity were evaluated by the modified NCI criteria and followed closely.
Dose limiting only if grade 4 thrombocytopenia or neutropenia persists for 7 days or greater.
Inability to continue with cycle 2 by 7 weeks for reasons other than progression of disease will also be considered a DLT.The National Cancer Institute Common Toxicity Criteria will be used to characterize toxicity.
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up to 7 weeks
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Recommended Dose Level of Flavopiridol
Periodo de tiempo: Up to 6 weeks
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Recommended dose determined by number of DLTs [non-hematologic toxicity grade 3 or greater (excluding not life-threatening transient liver function or transient electrolyte abnormalities, fatigue, or diarrhea resolving within 4 days), some grade 2 toxicity (i.e.
irreversible renal, chronic pulmonary, neurologic, or cardiac toxicity), hematologic toxicity of grade 4 thrombocytopenia/neutropenia persisting for 7 days or greater, or inability to continue cycle 2 by 7 weeks for reasons other than disease progression] and consideration of number of patients with severe tumor lysis requiring hemodialysis with dose 1.
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Up to 6 weeks
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Overall Response Rate (CR + PR) of Flavopiridol in Patients Evaluated Utilizing the Revised National Cancer Institute-sponsored Working Group Guidelines
Periodo de tiempo: Up to 2 years
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Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
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Up to 2 years
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Colaboradores e Investigadores
Patrocinador
Publicaciones y enlaces útiles
Publicaciones Generales
- Lin TS, Ruppert AS, Johnson AJ, Fischer B, Heerema NA, Andritsos LA, Blum KA, Flynn JM, Jones JA, Hu W, Moran ME, Mitchell SM, Smith LL, Wagner AJ, Raymond CA, Schaaf LJ, Phelps MA, Villalona-Calero MA, Grever MR, Byrd JC. Phase II study of flavopiridol in relapsed chronic lymphocytic leukemia demonstrating high response rates in genetically high-risk disease. J Clin Oncol. 2009 Dec 10;27(35):6012-8. doi: 10.1200/JCO.2009.22.6944. Epub 2009 Oct 13.
- Pierceall WE, Warner SL, Lena RJ, Doykan C, Blake N, Elashoff M, Hoff DV, Bearss DJ, Cardone MH, Andritsos L, Byrd JC, Lanasa MC, Grever MR, Johnson AJ. Mitochondrial priming of chronic lymphocytic leukemia patients associates Bcl-xL dependence with alvocidib response. Leukemia. 2014 Nov;28(11):2251-4. doi: 10.1038/leu.2014.206. Epub 2014 Jul 3. No abstract available.
- Woyach JA, Lozanski G, Ruppert AS, Lozanski A, Blum KA, Jones JA, Flynn JM, Johnson AJ, Grever MR, Heerema NA, Byrd JC. Outcome of patients with relapsed or refractory chronic lymphocytic leukemia treated with flavopiridol: impact of genetic features. Leukemia. 2012 Jun;26(6):1442-4. doi: 10.1038/leu.2011.375. Epub 2012 Jan 13. No abstract available.
- Ni W, Ji J, Dai Z, Papp A, Johnson AJ, Ahn S, Farley KL, Lin TS, Dalton JT, Li X, Jarjoura D, Byrd JC, Sadee W, Grever MR, Phelps MA. Flavopiridol pharmacogenetics: clinical and functional evidence for the role of SLCO1B1/OATP1B1 in flavopiridol disposition. PLoS One. 2010 Nov 1;5(11):e13792. doi: 10.1371/journal.pone.0013792.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (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 (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Enfermedades cardiovasculares
- Enfermedades Vasculares
- Enfermedades del sistema inmunológico
- Neoplasias por tipo histológico
- Neoplasias
- Trastornos linfoproliferativos
- Enfermedades linfáticas
- Trastornos inmunoproliferativos
- Enfermedades hematológicas
- Trastornos hemorrágicos
- Trastornos hemostáticos
- Paraproteinemias
- Trastornos de proteínas en sangre
- Neoplasias De Células Plasmáticas
- Leucemia de células B
- Linfoma
- Leucemia
- Macroglobulinemia de Waldenström
- Leucemia Linfocítica Crónica De Células B
- Leucemia Linfoide
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Inhibidores de enzimas
- Agentes antineoplásicos
- Sustancias de crecimiento
- Inhibidores del crecimiento
- Inhibidores de la proteína quinasa
- Alvocidib
Otros números de identificación del estudio
- NCI-2012-01435 (Identificador de registro: CTRP (Clinical Trial Reporting Program))
- P30CA016058 (Subvención/contrato del NIH de EE. UU.)
- U01CA076576 (Subvención/contrato del NIH de EE. UU.)
- CDR0000287197
- NCI-5746
- OSU-0055
- OSU 0055 (Otro identificador: Ohio State University Medical Center)
- 5746 (Otro identificador: CTEP)
- R21CA112947 (Subvención/contrato del NIH de EE. UU.)
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. .
Ensayos clínicos sobre Macroglobulinemia de Waldenström
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Weill Medical College of Cornell UniversityMayo Clinic; Janssen Scientific Affairs, LLCTerminadoMacroglobulinemia de Waldenström | Macroglobulinemia de Waldenstrom Recurrente | Macroglobulinemia de Waldenstrom refractaria | Enfermedad de Waldenström | Waldenström; Hipergammaglobulinemia | Macroglobulinemia de Waldenstrom de los ganglios linfáticos | Macroglobulinemia de Waldenstrom, sin mención...Estados Unidos
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M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Activo, no reclutandoMacroglobulinemia de Waldenstrom recurrente | Macroglobulinemia de Waldenstrom refractariaEstados Unidos
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BeiGeneReclutamientoMacroglobulinemia de Waldenström | Macroglobulinemia de Waldenstrom Recurrente | Macroglobulinemia de Waldenstrom refractariaEstados Unidos, Australia, Porcelana, España, Reino Unido
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Mayo ClinicNational Cancer Institute (NCI)Activo, no reclutandoMacroglobulinemia de Waldenström | Macroglobulinemia de Waldenstrom recurrente | Macroglobulinemia de Waldenstrom refractariaEstados Unidos
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Beijing InnoCare Pharma Tech Co., Ltd.Activo, no reclutandoMacroglobulinemia de Waldenstrom Recurrente | Macroglobulinemia de Waldenstrom refractariaPorcelana
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University of WashingtonNational Cancer Institute (NCI)TerminadoLinfoma recidivante de la zona marginal | Macroglobulinemia de Waldenström | Linfoma de zona marginal | Linfoma refractario de la zona marginal | Macroglobulinemia de Waldenstrom recurrente | Macroglobulinemia de Waldenstrom refractariaEstados Unidos
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Poitiers University HospitalReclutamientoMacroglobulinemia de Waldenstrom refractariaFrancia
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European Myeloma NetworkUniversitaire Ziekenhuizen KU Leuven; University of Roma La Sapienza; Hospital... y otros colaboradoresTerminadoMacroglobulinemia de WaldenstromGrecia
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Cancer Trials AustraliaHuman Genome Sciences Inc.DesconocidoMacroglobulinemia de Waldenstrom sintomáticaAustralia
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Mustang BioNational Cancer Institute (NCI)ReclutamientoLinfoma de células del manto recurrente | Linfoma de células del manto refractario | Linfoma de linfocitos pequeños, en recaída | Macroglobulinemia de Waldenstrom Recurrente | Linfoma no Hodgkin folicular de células B | Linfoma de células B refractario | Macroglobulinemia de Waldenstrom refractaria y otras condicionesEstados Unidos
Ensayos clínicos sobre alvocidib
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Sumitomo Pharma America, Inc.TerminadoLeucemia mieloide aguda (LMA)Estados Unidos
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National Cancer Institute (NCI)TerminadoLinfoma | Cáncer de intestino delgado | Cancer de prostata | Tumor sólido adulto no especificado, protocolo específicoEstados Unidos
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National Cancer Institute (NCI)Terminado
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Gynecologic Oncology GroupNational Cancer Institute (NCI)TerminadoCáncer endometrialEstados Unidos, Canadá, Noruega, Reino Unido, Australia
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National Cancer Institute (NCI)TerminadoCancer de prostataEstados Unidos
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NCIC Clinical Trials GroupTerminado
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Southwest Oncology GroupNational Cancer Institute (NCI)TerminadoCancer de RIÑONEstados Unidos
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National Cancer Institute (NCI)Terminado
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NCIC Clinical Trials GroupTerminadoSarcomaCanadá, Estados Unidos
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NCIC Clinical Trials GroupTerminado