Fludarabine Combined With Either Alemtuzumab or Rituximab in Treating Patients With Refractory or Relapsed B-Cell Chronic Lymphocytic Leukemia
Phase II Trial Comparing Combination Treatment With Fludarabine and Alemtuzumab to Fludarabine and Rituximab in Patients With B-Cell Chronic Lymphocytic Leukemia Requiring Treatment After First Line Therapy
RATIONALE: Drugs used in chemotherapy, such as fludarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies, such as alemtuzumab and rituximab, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining chemotherapy with monoclonal antibody therapy may kill more cancer cells. It is not yet known whether fludarabine is more effective when combined with alemtuzumab or with rituximab in treating chronic lymphocytic leukemia.
PURPOSE: Randomized phase II trial to compare the effectiveness of combining fludarabine with either alemtuzumab or rituximab in treating patients who have refractory or relapsed B-cell chronic lymphocytic leukemia.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
OBJECTIVES:
Primary
- Compare the complete response rate in patients with refractory or relapsed B-cell chronic lymphocytic leukemia treated with fludarabine and alemtuzumab vs fludarabine and rituximab.
Secondary
- Compare the overall response rate in patients treated with these regimens.
- Compare 1-year survival of patients treated with these regimens.
- Compare time to progression in patients treated with these regimens.
- Compare duration of response in patients treated with these regimens.
- Compare the adverse event profile of these regimens in these patients.
- Compare the molecular response rate in patients treated with these regimens.
- Compare lymphocyte and lymphocyte subset recovery (CD3, CD3/CD4, CD3/CD8, CD20) in patients treated with these regimens.
- Compare the time to complete response in patients treated with these regimens.
- Compare the rate of cytomegalovirus reactivation and time to reactivation in patients treated with these regimens.
OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to prior treatment with fludarabine (yes vs no). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive fludarabine IV over 30 minutes on days 1-5. At least 30 minutes before fludarabine administration, patients receive alemtuzumab subcutaneously (SC) on days 1-5.
- Arm II: Patients receive fludarabine as in arm I. At least 30 minutes before fludarabine administration, patients receive rituximab IV on days 1 and 4 of course 1 and on day 1 only in subsequent courses.
In both arms, treatment repeats every 28 days for 4-6 courses in the absence of disease progression or unacceptable toxicity. An interim assessment is performed during course 4. Patients achieving a partial response or stable disease receive 2 additional courses of therapy (for a total of 6 courses). Patients achieving a complete response (CR) do not receive further treatment beyond CR.
Patients are followed weekly for 2 months, monthly for 6 months, every 2 months for 6 months, and then every 6 months for 1 year.
PROJECTED ACCRUAL: A total of 150 patients (75 per treatment arm) will be accrued for this study.
Tipo de estudio
Fase
- Fase 2
Contactos y Ubicaciones
Ubicaciones de estudio
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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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Mississippi
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Jackson, Mississippi, Estados Unidos, 39202
- Jackson Oncology Associates, PLLC
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New Jersey
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New Brunswick, New Jersey, Estados Unidos, 08903
- Cancer Institute of New Jersey at Robert Wood Johnson University Hospital
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Pennsylvania
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Pittsburgh, Pennsylvania, Estados Unidos, 15224
- Western Pennsylvania Cancer Institute
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Pittsburgh, Pennsylvania, Estados Unidos, 15232
- Hillman Cancer Center at University of Pittsburgh Cancer Institute
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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:
Diagnosis of B-cell chronic lymphocytic leukemia (CLL), defined as:
- Peripheral lymphocyte count > 5,000/mm^3
- Clonal CD5-, CD19-, and CD23-positive lymphocytes
- Refractory to OR relapsed after prior first-line therapy
- No CNS involvement with CLL
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-2
Life expectancy
- Not specified
Hematopoietic
- See Disease Characteristics
Hepatic
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- Hepatitis B surface antigen negative
- Hepatitis C antibody negative
Renal
- Creatinine ≤ 1.5 times ULN
Immunologic
- No active cytomegalovirus
- No prior fludarabine-associated autoimmune hemolytic anemia or immune thrombocytopenic purpura
- No active infection requiring treatment with antibiotic, antiviral, or antifungal agents
- No prior significant allergic reaction to antibody therapies that required therapy to be discontinued
- HIV negative
Other
- No active secondary malignancy
- No other concurrent severe diseases or mental disorders
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy
- More than 4 weeks since prior alemtuzumab and/or rituximab
- No prior bone marrow transplantation
- No concurrent thrombopoietin or pegfilgrastim
Chemotherapy
- More than 3 weeks since prior fludarabine
Endocrine therapy
- Not specified
Radiotherapy
- Not specified
Surgery
- Not specified
Other
- More than 3 months since prior investigational drugs
- No other concurrent cytotoxic therapy
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Enmascaramiento: Ninguno (etiqueta abierta)
Colaboradores e Investigadores
Patrocinador
Investigadores
- Silla de estudio: Ann S. LaCasce, MD, Dana-Farber Cancer Institute
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
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 (Estimar)
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 del sistema inmunológico
- Neoplasias por tipo histológico
- Neoplasias
- Trastornos linfoproliferativos
- Enfermedades linfáticas
- Trastornos inmunoproliferativos
- Leucemia de células B
- Leucemia
- Leucemia Linfocítica Crónica De Células B
- Leucemia Linfoide
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Agentes antirreumáticos
- Antimetabolitos, Antineoplásicos
- Antimetabolitos
- Agentes antineoplásicos
- Agentes inmunosupresores
- Factores inmunológicos
- Agentes antineoplásicos inmunológicos
- Rituximab
- Fludarabina
- Fosfato de fludarabina
- Alemtuzumab
Otros números de identificación del estudio
- BRLX-FLUCAM106
- CDR0000365631 (Identificador de registro: PDQ (Physician Data Query))
- BRLX-STA1-03-058
- OHSU-HEM-03050-P
- DMS-F0334
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