- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT00055653
Donor Umbilical Cord Blood Transplantation in Treating Patients With Leukemia, Lymphoma, or Nonmalignant Hematologic Disorders
Unrelated Umbilical Cord Blood As An Alternate Source Of Stem Cells Transplantation
RATIONALE: Umbilical cord blood transplantation may be able to replace immune cells that were destroyed by the chemotherapy or radiation therapy that was used to kill cancer cells.
PURPOSE: Phase II trial to study the effectiveness of allogeneic umbilical cord blood transplantation in treating patients who have leukemia, lymphoma, or nonmalignant hematologic disorders.
Descripción general del estudio
Estado
Condiciones
Descripción detallada
OBJECTIVES:
- Determine 180-day survival in patients with malignant or nonmalignant hematologic diseases treated with allogeneic umbilical cord blood transplantation. (Severe aplastic anemia, Fanconi anemia, and marrow failure syndromes strata are closed to accrual; adult [over 18 years of age] patient stratum is closed to accrual.)
- Determine disease-free and long-term survival in patients treated with this regimen.
- Determine the incidence of neutrophil engraftment, primary and secondary graft failure, platelet engraftment, and red blood cell engraftment in patients treated with this regimen.
- Determine the incidence and severity of acute and chronic graft-versus-host disease in patients treated with this regimen.
- Determine the incidence of complications, including infection, veno-occlusive disease, and interstitial pneumonitis, in patients treated with this regimen.
- Determine the incidence of relapse, other malignancies, lymphoproliferative disorders, and posttransplantation myelodysplasia in patients treated with this regimen.
- Determine the immune reconstitution in patients treated with this regimen.
OUTLINE: This is a multicenter study. Patients are grouped according to the following strata:
- Stratum I: Malignant disease, 5/6 or 6/6 HLA match, age 18 and under
- Stratum II: Malignant disease, 4/6 HLA match, age 18 and under
- Stratum III: Malignant disease, 3/6 HLA match, age 18 and under
- Stratum IV: Malignant disease, 2/6 or 1/6 HLA match, age 18 and under
- Stratum V (closed to accrual): Severe aplastic anemia, Fanconi anemia, or other marrow failure syndrome
- Stratum VI: Inborn errors of metabolism/storage diseases and other nonmalignant diseases not included in stratum V
- Stratum VII: Malignant disease receiving alternative conditioning regimen comprising busulfan and melphalan
- Stratum VIII (closed to accrual): Adult patients (over age 18)
Conditioning therapy: Patients are assigned to 1 of 5 groups according to diagnosis.
- Group I (malignant disease or severe aplastic anemia [severe aplastic anemia closed to accrual]): Patients undergo total body irradiation (TBI) once or twice daily on days -8 to -4. Patients then receive cyclophosphamide IV on days -3 and -2, methylprednisolone IV on days -3 to 0, and antithymocyte globulin (ATG) IV once or twice daily on days -3 to -1.
- Group II (Fanconi anemia [closed to accrual]): Patients undergo TBI on day -6, and then receive cyclophosphamide IV and fludarabine IV on days -5 to -2, and methylprednisolone IV and ATG IV on days -5 to -1.
- Group III (inborn errors of metabolism/storage disease): Patients receive oral busulfan 4 times daily on days -9 to -6, cyclophosphamide as in group II, and methylprednisolone and ATG as in group I.
- Group IV (other nonmalignant diseases): Patients receive conditioning therapy as in group III. Patients with familial erythrophagocytic lymphohistiocytosis or Langerhans cell histiocytosis also receive etoposide on days -5 to -3.
- Group V (non-TBI regimen for leukemia patients under 2 years of age): Patients receive oral busulfan 4 times daily on days -8 to -5, melphalan IV on days -4 to -2, and methylprednisolone and ATG as in group I.
- Allogeneic umbilical cord blood transplantation: All patients undergo umbilical cord blood transplantation on day 0. Beginning on day 0 or 1, patients receive filgrastim (G-CSF) IV or subcutaneously daily until blood counts recover.
- Graft-versus-host disease prophylaxis: Patients receive cyclosporine (IV or oral) beginning between days -3 and -1 and continuing for 1 year after transplantation and methylprednisolone twice daily beginning on day 1 and continuing until blood counts recover.
Patients are followed weekly for 14 weeks, at 100 days, and at 4, 5, 6, 9, 12, 18, 24, and 36 months.
PROJECTED ACCRUAL: A total of 360 patients will be accrued for this study.
Tipo de estudio
Fase
- Fase 2
Contactos y Ubicaciones
Ubicaciones de estudio
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California
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Duarte, California, Estados Unidos, 91010-3000
- City of Hope Comprehensive Cancer Center
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Los Angeles, California, Estados Unidos, 90095-1781
- Jonsson Comprehensive Cancer Center, UCLA
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Los Angeles, California, Estados Unidos, 90027-0700
- Children's Hospital Los Angeles
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Orange, California, Estados Unidos, 92868
- Children's Hospital of Orange County
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San Francisco, California, Estados Unidos, 94143-1278
- Children's Medical Center, University of California San Francisco
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District of Columbia
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Washington, District of Columbia, Estados Unidos, 20010-2970
- Children's National Medical Center
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Indiana
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Indianapolis, Indiana, Estados Unidos, 46202-5289
- Indiana University Cancer Center
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Louisiana
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New Orleans, Louisiana, Estados Unidos, 70118
- Children's Hospital of New Orleans
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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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Michigan
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Grand Rapids, Michigan, Estados Unidos, 49503
- Spectrum Health and DeVos Children's Hospital
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Minnesota
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Minneapolis, Minnesota, Estados Unidos, 55455
- University of Minnesota Cancer Center
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Missouri
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Kansas City, Missouri, Estados Unidos, 64108
- Children's Mercy Hospital
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Saint Louis, Missouri, Estados Unidos, 63104-1095
- Cardinal Glennon Children's Hospital
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New Jersey
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Hackensack, New Jersey, Estados Unidos, 07601
- Hackensack University Medical Center
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New York
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Buffalo, New York, Estados Unidos, 14263-0001
- Roswell Park Cancer Institute
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Manhasset, New York, Estados Unidos, 11030
- North Shore University Hospital
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Rochester, New York, Estados Unidos, 14642
- James P. Wilmot Cancer Center at University of Rochester Medical Center
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North Carolina
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Durham, North Carolina, Estados Unidos, 27710
- Duke Comprehensive Cancer Center
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Ohio
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Cleveland, Ohio, Estados Unidos, 44106-5065
- Ireland Cancer Center
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Pennsylvania
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Pittsburgh, Pennsylvania, Estados Unidos, 15213
- Children's Hospital of Pittsburgh
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Tennessee
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Nashville, Tennessee, Estados Unidos, 37232-6310
- Vanderbilt-Ingram Cancer Center
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Texas
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Dallas, Texas, Estados Unidos, 75230
- Medical City Dallas Hospital
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Dallas, Texas, Estados Unidos, 75235
- Children's Medical Center of Dallas
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San Antonio, Texas, Estados Unidos, 78229
- Texas Transplant Institute
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Washington
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Seattle, Washington, Estados Unidos, 98109-1024
- Fred Hutchinson Cancer Research Center
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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 myeloid leukemia (AML)*
- With or without history of myelodysplastic syndromes (MDS)
- Patients in first complete remission (CR) (no greater than 5% blasts in marrow) with translocations t(8;21) and inv(16) are allowed provided they failed first-line induction therapy
Patients in first CR (no greater than 5% blasts in marrow) with translocations t(15;17) are allowed provided at least 1 of the following is true:
- Failed first-line induction therapy
- Molecular evidence of persistent disease
- No patients in first CR and with Down syndrome
Acute lymphoblastic leukemia (ALL)*, meeting 1 of the following criteria:
- Not in first CR (no greater than 5% blasts in marrow)
In first CR and high risk as defined by 1 of the following:
- Hypoploidy (no more than 44 chromosomes)
- Pseudodiploidy with translocations or molecular evidence of t(9;22), 11q23, or t(8;14) (excluding B-ALL) or +MLL gene rearrangement
One of the following elevated WBC levels:
- WBC greater than 100,000/mm^3 if 6 to 12 months of age
- WBC greater than 200,000/mm^3 if between 10 and 17 years of age
- WBC greater than 20,000/mm^3 if 18 years of age and over (adult [over 18 years of age] patient stratum closed to accrual)
- Failed to achieve CR after 4 weeks of induction therapy
B-ALL that is not in first CR or that meets at least 1 of the high-risk criteria specified above
- No translocation t(8;14)
- No blasts with surface immunoglobulins
- CD10 negative
- Undifferentiated leukemia*
- Infant leukemia*
- Biphenotypic leukemia*
Chronic myelogenous leukemia, meeting 1 of the following criteria:
- Accelerated phase
Chronic phase
- At least 1 year from diagnosis without an identified matched unrelated bone marrow donor AND unresponsive to or unable to tolerate interferon
- Blast crisis* (greater than 30% promyelocytes plus blasts in the marrow)
One of the following MDS:
- Refractory anemia
- Refractory anemia with ringed sideroblasts
- Refractory anemia with excess blasts (RAEB)
- RAEB in transformation
- Chronic myelomonocytic leukemia
- Paroxysmal nocturnal hemoglobinuria
Hodgkin's or non-Hodgkin's lymphoma beyond first CR or failed primary induction therapy
- Tumor displays chemosensitivity (greater than 50% reduction in mass size after the most recent therapy) NOTE: *Patients in third or greater medullary relapse or refractory disease (other than primary induction failures) or blast crisis receive the study busulfan/melphalan conditioning regimen)
OR
Diagnosis of one of the following nonmalignant diseases :
Acquired severe aplastic anemia (stratum closed to accrual)
- Unresponsive to medical therapy with anti-thymocyte globulin and/or cyclosporine
Inborn errors of metabolism, including, but not limited to the following:
- Hurler's syndrome
- Adrenoleukodystrophy
- Maroteaux-Lamy syndrome
- Globoid cell leukodystrophy
- Metachromatic leukodystrophy
- Fucosidosis
- Mannosidosis
Fanconi anemia documented by increased chromosomal fragility assays and meeting 1 of the following criteria (stratum closed to accrual):
Severe pancytopenia
- Absolute neutrophil count less than 500/mm^3
- Platelet count less than 20,000/mm^3
- Hemoglobin less than 8 g/dL
- Morphologic evidence of MDS with clonal chromosomal abnormalities
- Leukemia transformation
Other marrow failure syndromes, including any of the following (stratum closed to accrual):
- Blackfan-Diamond syndrome that is unresponsive to medical therapy
- Kostmann's congenital agranulocytosis unresponsive to medical therapy
- Congenital amegakaryocytic thrombocytopenia
- Thrombocytopenia absent radius
Combined immune deficiencies including, but not limited to the following:
- Severe combined immunodeficiency (SCID)
- Wiskott-Aldrich syndrome
- Leukocyte adhesion defect
- Chediak-Higashi disease
- X-linked lymphoproliferative disease
- Adenosine deaminase deficiency
- Purine nucleoside phosphorylase deficiency
- X-linked SCID
- Common variable immune deficiency
- Nezeloff's syndrome
- Cartilage hair hypoplasia
- Reticular dysgenesis
- No active CNS leukemia (cerebrospinal fluid with WBC greater than 5/mm^3 and malignant cells on cytospin)
- No SCID patients who do not require cytoreduction
- No dyskeratosis congenita
- No primary myelofibrosis
- No grade 3 or greater myelofibrosis
Familial erythrophagocytic lymphohistiocytosis patients must not have any of the following:
- Abnormal brain MRI
- Neurologic symptoms
- Lymphocytes and monocytes greater than 7/mm^3 in the cerebrospinal fluid
- No available 5/6 or 6/6 HLA-matched related donor
PATIENT CHARACTERISTICS:
Age
- 55 and under (over 18 closed to accrual)
Performance status
- Karnofsky 70-100% OR
- Lansky 50-100% (patients under 16 years old)
Life expectancy
- Not specified
Hematopoietic
- See Disease Characteristics
Hepatic
- SGOT less than 5 times upper limit of normal
- Bilirubin less than 2.5 mg/dL
Renal
- Creatinine normal for age OR
- Creatinine clearance or glomerular filtration rate greater than 50% of lower limit of normal
Cardiovascular
- LVEF greater than 40% at rest and must improve with exercise* OR
- Shortening fraction greater than 26%* NOTE: *If symptomatic
Pulmonary
- DLCO greater than 45% of predicted* (corrected for hemoglobin)
- FEV_1 and FEC greater than 45% of predicted (corrected for hemoglobin) OR
- Room air oxygen saturation greater than 85%* NOTE: *If symptomatic
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No uncontrolled viral, bacterial, or fungal infection
- HIV negative
PRIOR CONCURRENT THERAPY:
Biologic therapy
- See Disease Characteristics
- More than 12 months since prior allogeneic stem cell transplantation with cytoreductive preparative therapy
- More than 6 months since prior autologous stem cell transplantation
Chemotherapy
- See Biologic therapy
Endocrine therapy
- Not specified
Radiotherapy
- Not specified
Surgery
- Not specified
Other
- No prior enrollment on this study
- No continuous life support (e.g., mechanical ventilation) within 1 year after study transplantation (for patients with inborn errors of metabolism)
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Enmascaramiento: Ninguno (etiqueta abierta)
Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Silla de estudio: Philip L. McCarthy, MD, Roswell Park 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
Palabras clave
- Linfoma de células pequeñas no hendidas infantil recidivante
- linfoma de células grandes infantil recurrente
- anemia refractaria
- anemia refractaria con sideroblastos anillados
- 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 secundaria
- leucemia linfoblástica aguda infantil en remisión
- leucemia mieloide aguda infantil en remisión
- leucemia mielógena crónica en fase crónica
- leucemia mieloide crónica atípica
- enfermedad mielodisplásica/mieloproliferativa, inclasificable
- leucemia linfoblástica aguda infantil no tratada
- Linfoma de Hodgkin infantil recurrente/refractario
- leucemia mielógena crónica en fase blástica
- leucemia linfoblástica aguda infantil recurrente
- leucemia mielógena crónica en fase acelerada
- leucemia mieloide aguda infantil recurrente
- linfoma linfoblástico infantil recurrente
- leucemia aguda indiferenciada
- leucemia mieloide aguda infantil no tratada y otras neoplasias malignas mieloides
Términos MeSH relevantes adicionales
- Procesos Patológicos
- Enfermedades del sistema inmunológico
- Neoplasias por tipo histológico
- Neoplasias
- Trastornos linfoproliferativos
- Enfermedades linfáticas
- Trastornos inmunoproliferativos
- Enfermedad
- Enfermedades de la médula ósea
- Enfermedades hematológicas
- Condiciones precancerosas
- Linfoma
- Síndrome
- Síndromes mielodisplásicos
- Leucemia
- Preleucemia
- Trastornos mieloproliferativos
- Enfermedades mielodisplásicas-mieloproliferativas
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Agentes antiinfecciosos
- Agentes Autonómicos
- Agentes del sistema nervioso periférico
- Inhibidores de enzimas
- Agentes antiinflamatorios
- Agentes antirreumáticos
- Antimetabolitos, Antineoplásicos
- Antimetabolitos
- Agentes antineoplásicos
- Agentes inmunosupresores
- Factores inmunológicos
- Antieméticos
- Agentes Gastrointestinales
- Glucocorticoides
- Hormonas
- Hormonas, sustitutos hormonales y antagonistas hormonales
- Agentes neuroprotectores
- Agentes Protectores
- Agentes antineoplásicos, alquilantes
- Agentes alquilantes
- Agonistas mieloablativos
- Agentes dermatológicos
- Agentes antifúngicos
- Inhibidores de calcineurina
- Metilprednisolona
- Ciclofosfamida
- Melfalán
- Fludarabina
- Fosfato de fludarabina
- Busulfán
- Suero Antilinfocito
- Ciclosporina
- Ciclosporinas
Otros números de identificación del estudio
- CDR0000270487
- RPCI-DS-00-22
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