- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT00255710
Cyclophosphamide and/or Mycophenolate Mofetil With or Without Tacrolimus in Treating Patients Who Are Undergoing a Donor Bone Marrow or Peripheral Stem Cell Transplant for Hematologic Cancer
Nonmyeloablative Bone Marrow Transplants in Hematologic Malignancies: Dose Finding Study for Post-Transplant Immunosuppression
RATIONALE: Giving low doses of chemotherapy, such as fludarabine, and radiation therapy before a donor bone marrow or stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system 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 cyclophosphamide, mycophenolate mofetil, and tacrolimus after transplant may stop this from happening.
PURPOSE: This phase I trial is studying cyclophosphamide and/or mycophenolate mofetil with or without tacrolimus to see which is the best regimen in treating patients who are undergoing a donor bone marrow or stem cell transplant for hematologic cancer.
Descripción general del estudio
Estado
Condiciones
Descripción detallada
OBJECTIVES:
- Determine a minimal (short-duration) post-transplant immunosuppression regimen comprising cyclophosphamide and/or mycophenolate mofetil with or without tacrolimus that results in ≤ 20% incidence of grade II or higher acute graft-versus-host disease (GVHD) in patients with hematologic malignancies undergoing nonmyeloablative allogeneic bone marrow or peripheral blood stem cell transplantation from an HLA-identical related donor.
- Determine the post-transplant immunosuppression regimen that results in < 10% incidence of nonengraftment, defined as < 5% donor chimerism in peripheral blood at day 60, in these patients.
- Determine the incidence and severity of acute GVHD in patients treated with these regimens.
- Determine the frequency of mixed chimerism in patients treated with these regimens.
OUTLINE:
- Nonmyeloablative allogeneic bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT): Patients receive fludarabine IV on days -4 to -2 and undergo total-body irradiation on day -1. Patients undergo allogeneic BMT on day 0 or PBSCT on day 0 (and days 1 and 2, if needed). Patients receive filgrastim (G-CSF) beginning on day 5 and continuing until at least day 15 or until blood counts recover.
Sequentially increasing levels of post-transplant immunosuppression: Cohorts of patients are enrolled into 1 of the following regimens:
- Regimen 1 (post-BMT immunosuppression): Patients receive cyclophosphamide IV on day 3 only.
- Regimen 2 (post-BMT immunosuppression): Patients receive mycophenolate mofetil (MMF) once on day 3 and then twice daily on days 4-32.
- Regimen 3 (post-BMT immunosuppression): Patients receive cyclophosphamide IV on days 3 and 4 and MMF twice daily on days 4-33.
- Regimen 4 (post-PBSCT immunosuppression): Patients receive cyclophosphamide and MMF as in regimen 3.
- Regimen 5 (post-PBSCT immunosuppression): Patients receive cyclophosphamide and MMF as in regimen 3 and tacrolimus twice daily on days 4-33.
Cohorts of approximately 10-20 patients receive sequentially increasing levels of post-transplant immunosuppression until a minimal (short-duration) post-transplant immunosuppression regimen is identified. The minimal post-transplant immunosuppression regimen is defined as the regimen in which ≤ 3 of 10 or ≤ 6 of 20 patients develop grade II or higher acute graft-versus-host disease AND ≤ 2 of 10 or ≤ 4 of 20 patients fail to engraft 60 days post-transplantation. Once the minimal post-transplant immunosuppression regimen is identified, an additional 10 patients are treated with that regimen.
Patients are followed for 60 days after transplantation.
PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.
Tipo de estudio
Inscripción (Anticipado)
Fase
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
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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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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:
- Stage II or III multiple myeloma
- Amyloidosis
Myelofibrosis with ≥ 2 of the following high-risk features:
- Over 55 years of age
- Hemoglobin < 10 g/dL
- WBC < 3,000/mm^3 OR > 10,000/mm^3
- Platelet count < 100,000/mm^3
- Cytogenetic abnormalities
Mycosis fungoides, meeting 1 of the following criteria:
Stage IIB or III disease with evidence of histologic conversion to an aggressive lymphoma
- Must demonstrate chemosensitivity
- Stage IV disease
Paroxysmal nocturnal hemoglobinuria
- Not meeting criteria for other bone marrow transplantation (BMT) or treatment studies
Diagnosis of 1 of the following hematologic malignancies, for which patient is not eligible for potentially curative allogeneic BMT due to end-organ dysfunction, age 65 to 75, or the amount of prior chemotherapy:
Acute myeloid or acute lymphoblastic leukemia
- High-risk disease in first or second (or further) complete remission
Relapsed aggressive non-Hodgkin's lymphoma
- Not eligible for autologous or standard allogeneic BMT
Hodgkin's lymphoma in second or further complete or partial remission
- Not eligible for autologous or standard allogeneic BMT
Myelodysplastic syndromes or myelodysplastic/myeloproliferative diseases
Any of the following subtypes:
- Refractory anemia with excess blasts (RAEB)
- RAEB in transformation
- Chronic myelomonocytic leukemia
- Any morphologic subtype with multiple chromosomal abnormalities
- Any subset with life-threatening cytopenias in all 3 cell lines, defined as platelet count ≤ 20,000/mm^3, absolute neutrophil count ≤ 500/mm^3, and reticulocyte count ≤ 50,000/mm^3
Meets both of the following criteria:
- Less than 20% blasts by bone marrow biopsy
- Not eligible for standard allogeneic BMT
- No refractory anemia with ringed sideroblasts
- No 5q syndrome
Stage III or IV chronic lymphocytic leukemia
- Not meeting criteria for other BMT studies
Chronic myelogenous leukemia in first or second chronic phase
- Not meeting criteria for other BMT studies or treatment
Stage III or IV indolent small lymphocytic or follicular lymphoma
- Not eligible for autologous or standard allogeneic BMT or other active protocols at Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- Must have an HLA-identical related donor available
PATIENT CHARACTERISTICS:
Performance status
- ECOG 0-2
Life expectancy
- Not specified
Hematopoietic
- See Disease Characteristics
Hepatic
- Bilirubin ≤ 3.0 mg/dL
- AST ≤ 175 U/L
- ALT ≤ 200 U/L
Renal
- Creatinine ≤ 3.0 mg/dL
Cardiovascular
- LVEF ≥ 30%
Pulmonary
- FEV_1 ≥ 40% predicted
- Forced vital capacity ≥ 40% predicted
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
PRIOR CONCURRENT THERAPY:
Chemotherapy
- See Disease Characteristics
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Cuidados de apoyo
- Enmascaramiento: Ninguno (etiqueta abierta)
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
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Post-transplant immunosuppression regimen with ≤ 20% incidence of a grade II-IV graft-versus-host-disease (GVHD) and < 10% incidence of nonengraftment (< 5% donor chimerism) at day 60 following transplant
|
Incidence and severity of acute GVHD at day 60 following transplant
|
Frequency of mixed chimerism defined as any detectable donor cells at day 60 following transplant
|
Colaboradores e Investigadores
Colaboradores
Investigadores
- Silla de estudio: Carol A. Huff, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
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 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
- anemia refractaria con exceso de blastos
- anemia refractaria con exceso de blastos en transformación
- 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 mieloide aguda secundaria
- leucemia mielógena crónica en fase crónica
- amiloidosis sistémica primaria
- leucemia mieloide crónica atípica
- enfermedad mielodisplásica/mieloproliferativa, inclasificable
- leucemia mieloide aguda del adulto en remisión
- Linfoma difuso de células mixtas en adultos recidivante
- linfoma folicular de grado 1 en estadio III
- linfoma folicular de grado 2 en estadio III
- linfoma folicular de grado 1 en estadio IV
- linfoma folicular de grado 2 en estadio IV
- mieloma múltiple en estadio II
- mieloma múltiple en estadio III
- Linfoma de linfocitos pequeños en estadio III
- Linfoma de linfocitos pequeños en estadio IV
- linfoma linfoblástico adulto recurrente
- linfoma de células del manto recurrente
- leucemia linfocítica crónica en estadio III
- leucemia linfocítica crónica en estadio IV
- Linfoma de Hodgkin en adultos en estadio III
- Linfoma de Hodgkin en adultos en estadio IV
- micosis fungoide estadio III/síndrome de Sézary
- micosis fungoide estadio IV/síndrome de Sézary
- leucemia linfoblástica aguda del adulto en remisión
- mielofibrosis idiopática crónica
- micosis fungoide estadio II/síndrome de Sézary
- citopenia refractaria con displasia multilinaje
- Enfermedad de injerto contra huésped
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
- Enfermedades mielodisplásicas-mieloproliferativas
- Enfermedad de injerto contra huésped
- 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
- CDR0000449652
- P30CA006973 (Subvención/contrato del NIH de EE. UU.)
- P01CA015396 (Subvención/contrato del NIH de EE. UU.)
- JHOC-J0169
- WIRB-20020304
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