- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT00003816
Combination Chemotherapy and Donor Stem Cell Transplant in Treating Patients With Aplastic Anemia or Hematologic Cancer
Allogeneic Blood or Marrow Transplantation for Hematologic Malignancy and Aplastic Anemia
RATIONALE: Giving chemotherapy drugs and total-body irradiation before a donor stem cell helps stop the growth of cancer or abnormal cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. It is not yet known which combination chemotherapy regimen is most effective when given before a donor stem cell transplant in treating aplastic anemia or hematologic cancer.
PURPOSE: This phase II/III trial is studying different combination chemotherapy regimens to compare how well they work when given before donor stem cell transplant in treating patients with aplastic anemia or hematologic cancer.
Descripción general del estudio
Estado
Condiciones
Descripción detallada
OBJECTIVES:
- Compare the morbidity, mortality, and overall outcome of patients with severe aplastic anemia or hematologic malignancy treated with standard vs novel conditioning regimens followed by allogeneic stem cell transplantation.
- Examine the influence of donor histocompatibility on outcome by comparing matched/related, mismatched/related (with or without T-cell depletion), and matched/unrelated transplants with stratification for type of preparative regimen.
- Ensure that patients with uncommon diagnoses will be treated in a uniform fashion with the best therapy available.
OUTLINE: Patients are stratified according to risk of relapse (standard-risk: acute leukemia in first complete remission, chronic myelogenous leukemia in first chronic phase, lymphoma in sensitive first relapse or second remission, primary or untreated myelodysplastic syndromes, or untreated severe aplastic anemia vs high-risk: all others).
Patients are assigned to one of the following conditioning regimens based on diagnosis, risk of relapse, and donor relatedness:
- Regimen 1: Patients receive busulfan IV over 2 hours every 6 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2.
- Regimen 2: Patients receive cyclophosphamide IV over 2 hours on days -5 to -2 and anti-thymocyte globulin IV over 4-8 hours on days -5 to -3.
- Regimen 3: Patients receive cyclophosphamide IV over 2 hours on days -5 and -4 and total-body irradiation (TBI) twice daily on days -3 to -1.
- Regimen 4: Patients receive fludarabine IV over 30 minutes on days -6 to -2 and melphalan IV over 1 hour on days -3 and -2.
- Regimen 5: Patients receive etoposide IV over 26 hours beginning on day -5, cyclophosphamide IV over 2 hours on day -4, and TBI twice daily on days -3 to -1.
- Regimen 6: Patients receive cyclophosphamide IV over 24 hours, carboplatin IV over 24 hours, and thiotepa IV over 24 hours on days -7 to -4.
- Regimen 7: Patients receive fludarabine IV over 30 minutes on days -5 to -1 and anti-thymocyte globulin IV over 4-8 hours on days -5 to -2.
- Regimen 8: Patients receive cyclophosphamide IV over 2 hours on days -5 and -4, TBI twice daily on days -3 to -1, and anti-thymocyte globulin IV over 4-8 hours on days -3 to -1.
- Regimen 9: Patients receive busulfan IV over 2 hours every 6 hours and anti-thymocyte globulin IV over 4-8 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2.
All patients then receive donor stem cell infusions on day 0. Some patients may undergo involved-field radiotherapy 4-8 weeks after transplant.
Patients will be taken off study after a minimum of 4 years of follow up.
PROJECTED ACCRUAL: At least 405 patients will be accrued for this study within 5 years.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
- Fase 3
Contactos y Ubicaciones
Ubicaciones de estudio
-
-
New York
-
Buffalo, New York, Estados Unidos, 14263-0001
- Roswell Park Cancer Institute
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
DISEASE CHARACTERISTICS:
Diagnosis of one of the following:
Severe aplastic anemia as defined by either of the following:
- Marrow cellularity (< 25% [or 25-50% cellularity with < 30% of remaining cells hematopoietic in origin])
At least 2 of the following abnormal peripheral blood counts:
- Reticulocyte count < 1% (corrected for hematocrit)
- Platelet count < 20,000/mm^3
- Neutrophil count < 500/mm^3
Histologically confirmed hematologic malignancy, including any of the following:
Acute leukemia
- Resistant or recurrent disease after combination chemotherapy with at least one standard regimen OR in first remission and at high risk of relapse
- Acute myeloid leukemia (AML) (antecedent myelodysplastic syndromes [MDS], secondary AML, or high-risk cytogenetic abnormalities)
- Acute lymphoblastic leukemia (ALL) (high-risk cytogenetic abnormalities)
Chronic myeloid leukemia (CML)
- Chronic phase, accelerated phase, or blast phase
Myeloproliferative disorders or MDS, including any of the following:
- Myelofibrosis
- Polycythemia vera*
- Essential thrombocythemia*
- Refractory anemia
- Refractory anemia with excess blasts
- Refractory anemia with excess blasts in transformation
- Chronic myelomonocytic leukemia NOTE: * Only if transformed to AML or MDS
Lymphoproliferative disease
Recurrent or persistent, symptomatic disease after first-line chemotherapy, including any of the following:
- Chronic lymphocytic leukemia (CLL) (≥ 20% marrow involvement)
- Waldenstrom macroglobulinemia
- Low-grade non-Hodgkin lymphoma
Intermediate or high-grade non-Hodgkin lymphoma, meeting 1 of the following criteria:
- Resistant or recurrent disease after combination chemotherapy with one standard regimen
- Lymphoblastic lymphoma or small noncleaved cell lymphoma in first remission and at high risk of relapse
- CNS disease
- Bone marrow disease and LDH greater than 300
- Solid tumor that would otherwise be treated on RPCI-DS-9115 (or equivalent autologous stem transplant protocol) AND has a syngeneic donor
Autologous bone marrow transplant not possible (or desirable) due to 1 of the following:
- History of marrow tumor
- Inadequate marrow dose
- Abnormal marrow histology or function prior to storage
- Thrombocytopenia or leukopenia
- Marrow cellularity < 20%
Histocompatible donor identified
Well-matched donor, as defined by 1 of the following:
- Family member matched for 5 or 6 HLA specificities (A, B, DR)*
- Unrelated donor meeting compatibility criteria of the National Marrow Donor Program (matched for HLA A, B, and DRB1 antigens)*
- Identical twin sibling
- If a compatible cord blood donor is identified and there is no suitable unrelated donor available, patient may receive cord blood transplant NOTE: *Patients ≤ 25 years of age may be singly mismatched at the A or B loci
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:
- 4 to 70
Performance status:
- Zubrod 0-2 OR
- Karnofsky 70-100%
Life expectancy:
- Not specified
Hematopoietic:
- See Disease Characteristics
Hepatic:
- Bilirubin < 3 times normal (unless due to disease)
- Alkaline phosphatase < 3 times normal (unless due to disease)
- SGOT < 3 times normal (unless due to disease)
- Hepatitis B surface antigen negative
- No severe hepatic disease that would preclude study participation
Renal:
- Creatinine normal
- Creatinine clearance ≥ 50 mL/min
- No severe renal disease that would preclude study participation
Cardiovascular:
- Cardiac ventricular ejection fraction ≥ 50% by MUGA or echocardiogram
- No uncontrolled or severe cardiovascular disease (e.g., myocardial infarction, congestive heart failure, symptomatic angina, life threatening arrhythmia, or hypertension within the past 6 months)
Pulmonary:
- DLCO or DLVA ≥ 50% predicted (corrected for hemoglobin or alveolar ventilation)
Other:
- No serious concurrent medical or psychiatric illness
No other serious organ dysfunction (unless due to underlying disease), including the following:
- Uncontrolled bacterial, viral, or fungal infection
- Uncontrolled peptic ulcer disease
- Uncontrolled diabetes mellitus
- HIV negative
- Cytomegalovirus status known
- Not pregnant
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Not specified
Chemotherapy:
- See Disease Characteristics
- Pretransplant cytoreductive chemotherapy allowed for patients with relapsed or refractory disease
Endocrine therapy:
- Not specified
Radiotherapy:
Not eligible for total-body irradiation if prior radiotherapy exceeded the following limits:
- Mediastinum: 3,600 cGy
- Heart: 3,600 cGy
- Whole lungs: 1,200 cGy
- Small bowel: 3,600 cGy
- Kidneys: 1,200 cGy
- Whole liver: 1,600 cGy
- Cranial spinal: 3,600 cGy
- Brain: 4,000 cGy
- Retina: 4,000 cGy
Surgery:
- Not specified
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: No aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
---|---|
Experimental: Regimen 1
Patients receive busulfan IV over 2 hours every 6 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2.
|
Dado IV
Dado IV
|
Experimental: Regimen 2
Patients receive cyclophosphamide IV over 2 hours on days -5 to -2 and anti-thymocyte globulin IV over 4-8 hours on days -5 to -3.
|
Dado IV
Dado IV
|
Experimental: Regimen 3
Patients receive cyclophosphamide IV over 2 hours on days -5 and -4 and total-body irradiation (TBI) twice daily on days -3 to -1.
|
Dado IV
Given twice daily for 3 days
|
Experimental: Regimen 4
Patients receive fludarabine IV over 30 minutes on days -6 to -2 and melphalan IV over 1 hour on days -3 and -2.
|
Dado IV
Dado IV
|
Experimental: Regimen 5
Patients receive etoposide IV over 26 hours beginning on day -5, cyclophosphamide IV over 2 hours on day -4, and TBI twice daily on days -3 to -1.
|
Dado IV
Dado IV
Given twice daily for 3 days
|
Experimental: Regimen 6
Patients receive cyclophosphamide IV over 24 hours, carboplatin IV over 24 hours, and thiotepa IV over 24 hours on days -7 to -4.
|
Dado IV
Dado IV
Dado IV
|
Experimental: Regimen 7
Patients receive fludarabine IV over 30 minutes on days -5 to -1 and anti-thymocyte globulin IV over 4-8 hours on days -5 to -2.
|
Dado IV
Dado IV
|
Experimental: Regimen 8
Patients receive cyclophosphamide IV over 2 hours on days -5 and -4, TBI twice daily on days -3 to -1, and anti-thymocyte globulin IV over 4-8 hours on days -3 to -1.
|
Dado IV
Dado IV
Given twice daily for 3 days
|
Experimental: Regimen 9
Patients receive busulfan IV over 2 hours every 6 hours and anti-thymocyte globulin IV over 4-8 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2.
|
Dado IV
Dado IV
Dado IV
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
CR Rate
Periodo de tiempo: day 100
|
Rate of Complete Remission by Day +100
|
day 100
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Toxicity/TRM at Day 100
Periodo de tiempo: Day +100
|
Death due to treatment related causes before day +100 after BMT
|
Day +100
|
4 Year PFS
Periodo de tiempo: 4 years
|
progression free survival estimate at 4 years post BMT (events are disease progression/relapse and death due to any cause)
|
4 years
|
4 yr OS
Periodo de tiempo: 4-year
|
Overall survival estimate at 4 years post BMT
|
4-year
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Silla de estudio: Philip L. McCarthy, MD, Roswell Park Cancer Institute
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
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 (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
- tumor sólido infantil no especificado, protocolo específico
- tumor sólido adulto no especificado, protocolo específico
- mielofibrosis primaria
- 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
- anemia refractaria
- 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 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 recurrente en adultos
- leucemia mieloide crónica atípica
- enfermedad mielodisplásica/mieloproliferativa, inclasificable
- leucemia mieloide aguda del adulto en remisión
- Linfoma difuso de células pequeñas hendidas en adultos recidivante
- Linfoma difuso de células mixtas en adultos recidivante
- leucemia mielógena crónica en fase blástica
- leucemia mielógena crónica recidivante
- Macroglobulinemia de Waldenström
- linfoma folicular grado 1 recurrente
- linfoma folicular grado 2 recurrente
- linfoma de la zona marginal recurrente
- linfoma de linfocitos pequeños recurrente
- 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
- linfoma linfoblástico adulto recurrente
- linfoma de células del manto recurrente
- anemia aplásica
- leucemia linfocítica crónica refractaria
- Linfoma no Hodgkin cutáneo de células T recidivante
- leucemia/linfoma recurrente de células T en adultos
- linfoma intraocular
- linfoma angioinmunoblástico de células T
- linfoma anaplásico de células grandes
- micosis fungoide recurrente/síndrome de Sézary
- leucemia linfoblástica aguda recurrente en adultos
- policitemia vera
- trombocitemia esencial
- leucemia prolinfocítica
- leucemia linfoblástica aguda infantil recurrente
- leucemia mielógena crónica en fase acelerada
- leucemia linfoblástica aguda del adulto en remisión
- leucemia mieloide aguda infantil recurrente
- linfoma linfoblástico infantil recurrente
- leucemia aguda indiferenciada
- Leucemia de linfocitos granulares grandes de células T
- Linfoma de Burkitt
Términos MeSH relevantes adicionales
- Procesos Patológicos
- Enfermedades del sistema inmunológico
- Neoplasias por tipo histológico
- Trastornos linfoproliferativos
- Enfermedades linfáticas
- Trastornos inmunoproliferativos
- Enfermedad
- Enfermedades de la médula ósea
- Enfermedades hematológicas
- Condiciones precancerosas
- Trastornos de insuficiencia de la médula ósea
- Neoplasias
- Linfoma
- Síndrome
- Síndromes mielodisplásicos
- Leucemia
- Preleucemia
- Anemia
- Trastornos mieloproliferativos
- Enfermedades mielodisplásicas-mieloproliferativas
- Anemia Aplásica
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Inhibidores de enzimas
- Agentes antirreumáticos
- Antimetabolitos, Antineoplásicos
- Antimetabolitos
- Agentes antineoplásicos
- Agentes inmunosupresores
- Factores inmunológicos
- Agentes antineoplásicos, alquilantes
- Agentes alquilantes
- Agonistas mieloablativos
- Agentes antineoplásicos, fitogénicos
- Inhibidores de la topoisomerasa II
- Inhibidores de la topoisomerasa
- Ciclofosfamida
- Carboplatino
- Etopósido
- Melfalán
- Fludarabina
- Fosfato de fludarabina
- Tiotepa
- Busulfán
- Suero Antilinfocito
Otros números de identificación del estudio
- RP 98-15 (Otro identificador: Roswell Park Cancer Institute)
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