- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT00134004
Fludarabine, Cyclophosphamide, and Total-Body Irradiation in Treating Patients Who Are Undergoing a Donor Bone Marrow Transplant for Hematologic Cancer
A Phase II Trial of Non-Myeloablative Conditioning and Transplantation of Partially HLA-Mismatched Bone Marrow for Patients With Hematologic Malignancies
RATIONALE: Giving low doses of chemotherapy, such as fludarabine and cyclophosphamide, and radiation therapy before a donor bone marrow transplant helps stop the growth of cancer cells. Giving chemotherapy or radiation therapy before or after transplant also stops the patient's immune system from rejecting the donor's bone marrow stem cells. The donated stem cells may replace the patient's immune system cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus and mycophenolate mofetil after the transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well giving fludarabine and cyclophosphamide together with total-body irradiation works in treating patients who are undergoing a donor bone marrow transplant for hematologic cancer.
Descripción general del estudio
Estado
Condiciones
Descripción detallada
OBJECTIVES:
- Determine transplant-related mortality, risk of relapse, and progression-free survival of patients with standard- or high-risk hematologic malignancies undergoing nonmyeloablative conditioning comprising fludarabine, cyclophosphamide, and total-body irradiation followed by HLA-haploidentical allogeneic bone marrow transplantation.
- Determine donor hematopoietic chimerism in patients' peripheral blood at 30, 60, and 180 days after transplantation.
- Determine hematologic and nonhematologic toxic effects of this regimen in these patients.
- Determine, when feasible, surface expression of HLA molecules and death receptors, sensitivity to cytotoxic lymphocytes, and expression of anti-apoptotic genes (e.g., Bcl-2, Bcl-xL, X-IAP, and c-FLIP) in cancer cells from patients who relapse after treatment with this regimen.
OUTLINE: This is a multicenter study. Patients are stratified according to risk of relapse (standard [defined as ≤ 30% risk] vs high [defined as ≥ 70% risk]).
- Nonmyeloablative conditioning regimen: Patients receive fludarabine IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1-2 hours on days -6 and -5. Patients undergo total body irradiation on day -1.
- Allogeneic bone marrow transplantation: Patients undergo donor bone marrow infusion on day 0.
- Post-transplantation therapy: Patients receive cyclophosphamide IV over 1-2 hours on days 3 and 4.
- Graft-vs-host disease prophylaxis: Beginning on day 5, patients receive oral mycophenolate mofetil 3 times daily until day 35 and tacrolimus IV (then changing to orally) twice daily until day 180.
Treatment continues in the absence of disease progression.
After completion of study transplantation, patients are followed on days 30, 60, 100, and 180; at 1 year; and then annually for 4 additional years.
PROJECTED ACCRUAL: A total of 75-100 patients will be accrued for this study within 3-4 years.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
Contactos y Ubicaciones
Ubicaciones de estudio
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Georgia
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Atlanta, Georgia, Estados Unidos, 30342
- Blood and Marrow Transplant Program at Northside Hospital
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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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Pennsylvania
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Philadelphia, Pennsylvania, Estados Unidos, 19102-1192
- Hahnemann University Hospital
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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 1 of the following hematologic malignancies:
Acute leukemia
- In second or subsequent complete remission (CR), as defined by absence of abnormal blast population by flow cytometry
In first CR with any of the following poor-risk cytogenetic features:
- Alteration of chromosome 5 or 7
- Multiple abnormalities
- Philadelphia chromosome positive
Chronic phase chronic myelogenous leukemia (CML)
- In first chronic phase and refractory to interferon alfa or imatinib mesylate
- In second or subsequent chronic phase
Chronic lymphocytic leukemia, meeting 1 of the following criteria:
- Received prior chemotherapy with a nucleoside analog and had remission lasting < 6 months
Received 1 prior therapy and has any of the following high-risk features:
- Cytogenetic abnormalities of 17p, 11q
- Mutations of the Zap70 gene
- Somatically unmutated immunoglobulin heavy chain variable region genes
Hodgkin's lymphoma
Ineligible for autologous stem cell transplantation (SCT) due to any of the following exclusion factors:
- LVEF < 45%
- FEV_1 or FVC < 50% of predicted (75% of predicted in patients with prior thoracic or mantle radiotherapy)
- Total bilirubin > 2.0 mg/dL (unless documented Gilbert's disease)
- Creatinine > 2.0 mg/dL
Non-Hodgkin's lymphoma (NHL)
- Low-grade NHL allowed provided patient had a remission duration of < 1 year after administration of any established, multi-agent chemotherapy regimen (e.g., CVP, CHOP, or rituximab in combination with CHOP)
- Intermediate- or high-grade NHL allowed provided patient is ineligible for autologous SCT according to the criteria listed above
- Multiple myeloma
- Myelodysplastic syndromes
- Paroxysmal nocturnal hemoglobinuria
Chronic myeloproliferative disorders other than CML, including any of the following:
- Chronic myelomonocytic leukemia
- Agnogenic myeloid metaplasia (or myeloid metaplasia with myelofibrosis), with hemoglobin < 10 g/dL OR WBC < 4,000/mm^3 or > 30,000/mm^3
Polycythemia vera or essential thrombocythemia in "spent" phase, with a history of 2 of the following:
- Marrow fibrosis
- Splenomegaly
- Cytopenia (i.e., absolute neutrophil count < 1,500/mm^3, platelet count < 100,000/mm^3, hemoglobin < 10 g/dL)
- Polycythemia vera or essential thrombocythemia with transformation to myelodysplastic syndromes or acute myeloid leukemia (requires treatment to achieve < 20% blasts in marrow)
- No smoldering myeloma
- Patients with acute myeloid leukemia or myelodysplastic syndromes must have had comprehensive cytogenetic evaluation of bone marrow specimen during active disease
- Ineligible for or refused bone marrow transplantation from an HLA-matched sibling or unrelated donor
- Ineligible for or refused autologous SCT
Must have an HLA mismatched (i.e., 3/6, 4/6, or 5/6) related (first-degree relative)* donor available
- Donor ≥ 18 years of age NOTE: *Patients with an inherited recombinant HLA haplotype may receive marrow from the parent in whose gamete the recombination occurred
NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.
PATIENT CHARACTERISTICS:
Age
- 6 months to 74 years
Performance status
- ECOG 0-1
Life expectancy
- Not specified
Hematopoietic
- See Disease Characteristics
Hepatic
- See Disease Characteristics
- Bilirubin < 3.1 mg/dL
Renal
- See Disease Characteristics
Cardiovascular
- See Disease Characteristics
- LVEF ≥ 35%
Pulmonary
- See Disease Characteristics
- FEV_1 or FVC ≥ 40% of predicted in patients without prior thoracic or mantle radiotherapy (60% of predicted in patients with prior thoracic or mantle radiotherapy)
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
- Geographically accessible
- No debilitating medical or psychiatric illness that would preclude giving informed consent or receiving optimal treatment or follow-up
PRIOR CONCURRENT THERAPY:
Biologic therapy
- See Disease Characteristics
- No prior transfusions from donor
Chemotherapy
- See Disease Characteristics
Endocrine therapy
- Not specified
Radiotherapy
- See Disease Characteristics
Surgery
- Not specified
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: Mini-haplo Transplant
Non-myeloablative haploidentical bone marrow transplant with a fludarabine, cyclophosphamide (Cy), TBI (total body irradiation) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis.
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Transplant-related Mortality
Periodo de tiempo: Cumulative incidence for the entire study, up to 11 years
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Percentage of participants who die for any reason other than recurrence of disease.
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Cumulative incidence for the entire study, up to 11 years
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Relapse Rate
Periodo de tiempo: Cumulative incidence for the entire study, up to 11 years
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Percentage of participants who experience disease relapse.
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Cumulative incidence for the entire study, up to 11 years
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Progression-free Survival
Periodo de tiempo: 2 years
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Percentage of participants who do not experience disease relapse, disease progression, or death.
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2 years
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Graft Failure Rate
Periodo de tiempo: Cumulative incidence for the entire study, up to 11 years
|
Percentage of participants who experienced failure to engraft (also called graft failure or graft rejection).
Failure to engraft is defined as <5% donor chimerism and absence of relapse or any other reason for that chimerism value.
All participants who met this criterion were included in this outcome measure.
|
Cumulative incidence for the entire study, up to 11 years
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Hematologic and Non-hematologic Toxicities as Measured by NCI Common Toxicity Criteria for Adverse Events, v 3.0 Weekly Until 1 Year After Transplantation
Periodo de tiempo: 1 year
|
Percentage of study participants who experienced a serious adverse event (SAE) within 1 year of bone marrow transplant.
Complete data is provided in the Adverse Event tables.
|
1 year
|
Colaboradores e Investigadores
Colaboradores
Investigadores
- Silla de estudio: Ephraim J. Fuchs, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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
Palabras clave
- Linfoma difuso de células grandes en adultos en estadio III
- Linfoma inmunoblástico de células grandes en adultos en estadio III
- Linfoma de Burkitt en adultos en estadio III
- linfoma folicular de grado 3 en estadio IV
- Linfoma difuso de células grandes en adultos en estadio IV
- Linfoma inmunoblástico de células grandes en adultos en estadio IV
- Linfoma de Burkitt en adultos en estadio IV
- linfoma folicular grado 3 recurrente
- Linfoma difuso de células grandes en adultos recidivante
- Linfoma inmunoblástico de células grandes en adultos recidivante
- Linfoma de Burkitt en adultos recidivante
- Linfoma de células pequeñas no hendidas infantil recidivante
- linfoma de células grandes infantil recurrente
- leucemia mielomonocítica crónica
- síndromes mielodisplásicos de novo
- síndromes mielodisplásicos previamente tratados
- síndromes mielodisplásicos secundarios
- leucemia mieloide aguda en adultos con anomalías 11q23 (MLL)
- leucemia mieloide aguda en adultos con inv(16)(p13;q22)
- leucemia mieloide aguda en adultos con t(15;17)(q22;q12)
- leucemia mieloide aguda en adultos con t(16;16)(p13;q22)
- leucemia mieloide aguda en adultos con t(8;21)(q22;q22)
- leucemia linfoblástica aguda infantil en remisión
- leucemia mieloide aguda infantil en remisión
- leucemia mielógena crónica en fase crónica
- leucemia mieloide cronica infantil
- síndromes mielodisplásicos infantiles
- leucemia mieloide aguda del adulto en remisión
- linfoma de Hodgkin adulto recurrente
- Linfoma de Hodgkin infantil recurrente/refractario
- Linfoma difuso de células pequeñas hendidas en adultos recidivante
- Linfoma difuso de células mixtas en adultos recidivante
- leucemia mielógena crónica recidivante
- linfoma folicular de grado 1 en estadio III
- linfoma folicular de grado 2 en estadio III
- linfoma folicular de grado 3 en estadio III
- Linfoma difuso de células pequeñas hendidas en adultos en estadio III
- Linfoma difuso de células mixtas en adultos en estadio III
- linfoma folicular de grado 1 en estadio IV
- linfoma folicular de grado 2 en estadio IV
- Linfoma difuso de células pequeñas hendidas en adultos en estadio IV
- Linfoma difuso de células mixtas en adultos en estadio IV
- linfoma de células del manto en estadio III
- linfoma de células del manto en estadio IV
- mieloma múltiple en estadio II
- mieloma múltiple en estadio III
- linfoma folicular grado 1 recurrente
- linfoma folicular grado 2 recurrente
- Linfoma folicular grado 1 en estadio II no contiguo
- Linfoma folicular grado 2 no contiguo en estadio II
- Linfoma difuso de células pequeñas hendidas en adultos no contiguos en estadio II
- Linfoma de linfocitos pequeños no contiguos en estadio II
- Linfoma no contiguo de la zona marginal en estadio II
- linfoma de la zona marginal recurrente
- linfoma de linfocitos pequeños recurrente
- Linfoma de linfocitos pequeños en estadio III
- linfoma de la zona marginal en estadio III
- Linfoma de linfocitos pequeños en estadio IV
- linfoma de la zona marginal en estadio IV
- Linfoma extraganglionar de células B de la zona marginal de tejido linfoide asociado a mucosas
- linfoma de células B de la zona marginal ganglionar
- linfoma esplénico de la zona marginal
- mieloma múltiple en estadio I
- linfoma linfoblástico adulto recurrente
- linfoma de células del manto recurrente
- leucemia linfocítica crónica refractaria
- Linfoma de Hodgkin en adultos en estadio III
- Linfoma de Hodgkin en adultos en estadio IV
- Linfoma linfoblástico en adultos en estadio III
- Linfoma linfoblástico en adultos en estadio IV
- mieloma múltiple refractario
- policitemia vera
- trombocitemia esencial
- Linfoma de células del manto en estadio II no contiguo
- Linfoma difuso de células grandes en adultos no contiguos en estadio II
- Linfoma difuso de células mixtas en adultos no contiguos en estadio II
- Linfoma linfoblástico no contiguo en adultos en estadio II
- Linfoma folicular grado 3 no contiguo en estadio II
- leucemia linfoblástica aguda del adulto en remisión
- Linfoma de Burkitt en adultos no contiguos en estadio II
- Linfoma inmunoblástico de células grandes en adultos en estadio II no contiguo
- linfoma linfoblástico infantil recurrente
- mielofibrosis idiopática crónica
Términos MeSH relevantes adicionales
- Procesos Patológicos
- Enfermedades cardiovasculares
- Enfermedades Vasculares
- Enfermedades del sistema inmunológico
- Neoplasias por tipo histológico
- Neoplasias
- Trastornos linfoproliferativos
- Enfermedades linfáticas
- Trastornos inmunoproliferativos
- Enfermedad
- Enfermedades de la médula ósea
- Enfermedades hematológicas
- Trastornos hemorrágicos
- Trastornos hemostáticos
- Paraproteinemias
- Trastornos de proteínas en sangre
- Condiciones precancerosas
- Linfoma
- Síndrome
- Síndromes mielodisplásicos
- Mieloma múltiple
- Neoplasias De Células Plasmáticas
- Leucemia
- Preleucemia
- Plasmacitoma
- Trastornos mieloproliferativos
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Agentes antiinfecciosos
- Inhibidores de enzimas
- Agentes antirreumáticos
- Antimetabolitos, Antineoplásicos
- Antimetabolitos
- Agentes antineoplásicos
- Agentes inmunosupresores
- Factores inmunológicos
- Agentes antineoplásicos, alquilantes
- Agentes alquilantes
- Agonistas mieloablativos
- Agentes antibacterianos
- Antibióticos, Antineoplásicos
- Agentes antituberculosos
- Antibióticos, Antituberculosos
- Inhibidores de calcineurina
- Ciclofosfamida
- Fludarabina
- Fosfato de fludarabina
- Tacrolimus
- Ácido micofenólico
Otros números de identificación del estudio
- J0457 CDR0000440990
- P30CA006973 (Subvención/contrato del NIH de EE. UU.)
- P01CA015396 (Subvención/contrato del NIH de EE. UU.)
- JHOC-J0457 (Otro identificador: Johns Hopkins SKCCC)
- JHOC-04072704
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