Células T Autólogas Expandidas Ex-Vivo para Leucemia Mielógena Crónica (LMC) Después de Autotrasplante
Este estudio de fase 2 tiene como objetivo evaluar la respuesta, como mejoras genéticas o moleculares mayores, dentro de los 12 meses después de completar la terapia utilizando células T autólogas expandidas ex-vivo en individuos con Leucemia Mielógena Crónica (LMC) después de un autotransplante, así como también monitorear la tasa de mortalidad.
filgrastim
+ recombinant interferon alfa
+ sargramostim
Enfermedades de la Médula Ósea+10
+ Enfermedad Crónica
+ Enfermedades Hematológicas
Estudio de Tratamiento
Resumen
Fecha de inicio: 1 de marzo de 1999
Fecha en la que se inscribió al primer participante.OBJECTIVES: Determine the feasibility of ex vivo expansion and reinfusion of autologous CD4+ T cells after interferon therapy or high-dose chemotherapy with CD34-selected autologous peripheral blood stem cell rescue in patients with chronic phase chronic myelogenous leukemia (CML). Determine the frequency of hematologic, cytogenetic, and molecular remissions of CML following infusion of ex vivo expanded T cells. OUTLINE: Patients undergo mononuclear cell leukapheresis to obtain T cells for ex-vivo expansion, preferably before they receive interferon alfa subcutaneously (SC) daily on a therapeutic trial. At least 1 month after interferon is stopped, mobilization chemotherapy is administered. Patients receive cyclophosphamide IV over 12 hours on day 0, etoposide IV over 2 hours on day 1, sargramostim (GM-CSF) SC on days 3 and 4, and filgrastim (G-CSF) SC beginning on day 5. Peripheral blood stem cells (PBSC) are collected by leukapheresis when blood cell counts have recovered. Approximately 2-3 weeks later, high-dose chemotherapy begins. Patients receive gemcitabine IV over 100 minutes on day -5, carmustine IV over 2 hours on day -2, followed 6 hours later by gemcitabine IV again, and melphalan IV over 20 minutes on day -1. CD34 selected PBSCs are infused on day 0, at least 18 hours after melphalan administration. Patients receive GM-CSF SC beginning on day 1 and continuing until blood cell counts recover. Patients then receive ex vivo expanded autologous T cells on day 14 after autotransplantation. Interferon alfa is administered three times a week starting about 3 months after transplantation. Patients who only receive expanded T cells, without high-dose chemotherapy and autotransplantation, but show no response after 3 months, may proceed to autotransplantation followed by a second ex vivo expanded T-cell infusion. Patients are followed at 1, 2, 3, 6, 9, and 12 months, then every 6 months thereafter. PROJECTED ACCRUAL: A total of 7-22 patients will be accrued for this study.
Protocolo
Esta sección proporciona detalles del plan del estudio, incluyendo cómo está diseñado y qué se está evaluando.Se reclutarán 22 pacientes
Número total de participantes que el ensayo clínico espera reclutar.Estudio de Tratamiento
Elegibilidad
Los investigadores buscan pacientes que cumplan ciertos criterios, conocidos como criterios de elegibilidad: estado general de salud o tratamientos previos.Cualquier sexo
Sexo biológico de los participantes elegibles para inscribirse.Hasta 120 Años
Rango de edades de los participantes que pueden unirse al estudio.Voluntarios sanos no permitidos
Indica si personas sanas, sin la condición que se estudia, pueden participar.Condiciones
Patología
Criterios
DISEASE CHARACTERISTICS: Diagnosis of chronic myelogenous leukemia based on clinical features and molecular evidence for bcr/abl gene rearrangement First or second chronic phase at the time of stem cell collection Ineligible for allogeneic transplantation Should receive interferon alfa (IFN-A) with or without low-dose cytarabine for at least 3-6 months before autotransplantation and meet one of the following conditions: After 3 months of IFN-A, hematologic response is partial or less and poor clinical feature was present at diagnosis After 6 months of IFN-A, hematologic response is partial or complete (but 100% Ph+) and poor clinical feature was present at diagnosis After 9 or 12 months of IFN-A, no cytogenetic response occurred (100% Ph+), regardless of pretreatment clinical features After at least 12 months of IFN-A (or on 2 separate tests, 3 months apart), only minor cytogenetic response (35-90% Ph+) occurred, then eligible for ex vivo expanded autologous T cells only (without high-dose chemotherapy or autografting) or high-dose therapy plus autographing at physicians' discretion After at least 12 months of IFN-A (or on 2 tests, 3 months apart), major but not complete cytogenetic response (0-34% Ph+) occurred, then eligible for ex vivo expanded autologous T cells only (without high-dose chemotherapy or autografting) After at least 18 months of IFN-A, complete cytogenetic response (0% Ph+) occurred but remain positive for BCR/ABL gene rearrangement then eligible for ex vivo expanded autologous T cells only (without high-dose chemotherapy or autografting) Unsatisfactory response to prior STI571 allowed (regardless of prior IFN-A) PATIENT CHARACTERISTICS: Age: Not specified Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Bilirubin no greater than 2 times upper limit of normal (ULN) (unless due to Gilbert's disease) AST and ALT no greater than 2 times ULN (unless liver involvement with CML) Renal: Creatinine no greater than 2.5 mg/dL Cardiovascular: LVEF at least 45% (lower allowed if no significant functional impairment) Pulmonary: FEV_1, FVC, and DLCO at least 50% predicted Other: No active infections requiring IV antibiotics HIV negative Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics At least 1 month since prior interferon Chemotherapy: At least 1 week since hydroxyurea before leukapheresis Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified
Plan de Estudio
Conoce todos los tratamientos administrados en este estudio, su descripción detallada y en qué consisten.Objetivos del Estudio
Objetivos Primarios
Centros del Estudio
Estos son los hospitales, clínicas o centros de investigación donde se lleva a cabo el estudio. Puedes encontrar la ubicación más cercana a ti y su estado de reclutamiento.Este estudio tiene una ubicación
Greenebaum Cancer Center at University of Maryland Medical Center
Baltimore, United StatesAbrir Greenebaum Cancer Center at University of Maryland Medical Center en Google Maps