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Flavopiridol in Treating Patients With Previously Treated Chronic Lymphocytic Leukemia or Lymphocytic Lymphoma

2 de junio de 2017 actualizado por: National Cancer Institute (NCI)

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)

This phase I/II trial studies the side effects and best dose of flavopiridol in treating patients with previously treated chronic lymphocytic leukemia or lymphocytic lymphoma. Drugs used in chemotherapy such as flavopiridol work in different ways to stop cancer cells from dividing so they stop growing or die.

Descripción general del estudio

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

Intervencionista

Inscripción (Actual)

52

Fase

  • Fase 2
  • Fase 1

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

    • Ohio
      • Columbus, Ohio, Estados Unidos, 43210
        • Ohio State University Medical Center

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:

  • 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

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: N / A
  • Modelo Intervencionista: Asignación de un solo grupo
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
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.
Dado IV
Otros nombres:
  • FLAVO
  • flavopiridol
  • HMR 1275
  • L-868275

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Number of Patients With Dose Limiting Toxicities (DLTs)
Periodo de tiempo: up to 7 weeks
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.
up to 7 weeks
Recommended Dose Level of Flavopiridol
Periodo de tiempo: Up to 6 weeks
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.
Up to 6 weeks

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
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
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
Up to 2 years

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Publicaciones y enlaces útiles

La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.

Publicaciones Generales

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)

1 de abril de 2003

Finalización primaria (Actual)

1 de febrero de 2009

Finalización del estudio (Actual)

1 de febrero de 2009

Fechas de registro del estudio

Enviado por primera vez

7 de abril de 2003

Primero enviado que cumplió con los criterios de control de calidad

8 de abril de 2003

Publicado por primera vez (Estimar)

9 de abril de 2003

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

2 de julio de 2017

Última actualización enviada que cumplió con los criterios de control de calidad

2 de junio de 2017

Última verificación

1 de junio de 2017

Más información

Términos relacionados con este estudio

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. .

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