Estudio de leucemia y linfoma de células B maduras III
This is a phase III clinical trial using risk-adapted therapy. Treatment outcomes for children with B-cell NHL are excellent. Further improvements in outcome will likely be achieved through more focused study of the biology of the tumors and prospective studies of the late effects of treatment. Toward this end, this study features a spectrum of prospective biologic and late effect studies performed in patients treated with a modified regimen derived from the very successful LMB-96 regimen.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
- This study will perform analysis of newly diagnosed mature B-cell lymphomas (e.g. Burkitt lymphoma/leukemia, DLBCL, and MLBCL) obtained from participants in different parts of the world.
- This study will describe the types and frequency of mutations in the ARF-HDM2-TP53 pathway, in B-cell lymphomas in the United States and that found in selected geographic regions of the world.
- This study will describe the expression of ARF-HDM2-TP53 and PUMA-associated pathways in B-cell lymphomas in the United States and that found in B-cell lymphomas of other selected geographic regions of the world.
- This study will describe the pattern and frequency of XLP gene mutations presenting with B-cell lymphomas in the United States and selected geographic regions.
- This study will describe the frequency of EBV-positive B-cell lymphomas in the United States and selected geographic regions of the world: and will describe the pattern of EBV protein and gene expression (e.g., EBNA 3) in EBV-positive lymphomas and the study will compare patterns of EBV protein and gene expression with clinical, laboratory and outcome data.
Exploratory Aims:
To estimate the complete response rate, event-free survival, and overall survival rates in patients with Burkitt lymphoma (BL), Burkitt leukemia/B-cell acute leukemia (B-ALL) and diffuse large B-cell lymphoma (DLBCL) treated with a stage-adapted regimen based on the St. Jude B-cell II protocol.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
- Fase 3
Contactos y Ubicaciones
Ubicaciones de estudio
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Cairo, Egipto, 11787
- Children's Cancer Hospital
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California
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San Diego, California, Estados Unidos, 92123
- Rady Children's Hospital San Diego
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Tennessee
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Memphis, Tennessee, Estados Unidos, 38105
- St. Jude Children's Research Hospital
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Singapore, Singapur, 119228
- National University Health System
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
St. Jude participants and collaborating sites participating in therapeutic and biological objectives:
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Participant must have a histologic diagnosis of a mature B cell lymphoma (e.g., Burkitt lymphoma/leukemia, atypical Burkitt lymphoma, diffuse large B-cell lymphoma, mediastinal large B-cell lymphoma, mature B-cell lymphoma NOS) as defined in the WHO classification.
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Participant must be previously untreated, (no more than 72 hours of steroids, one intrathecal chemotherapy treatment, and/or emergency radiation).
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Participant must be < 22 years of age at the time of diagnosis
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For selected higher-risk CD20+ Group B and all CD20+ Group C participants receiving rituximab only (e.g., those with MLBLC, Stage III with LDH ≥ 2 times upper limit of normal (ULN), and/or bone marrow/CNS involvement: All participants who will receive rituximab must have hepatitis screening prior to enrollment. Participants whose results indicate that they are carrier of hepatitis B can still be treated per Group B or C but will NOT receive rituximab. This screening must be done for eligibility for participants who will receive rituximab, BUT the results are not needed prior to enrollment:
- Hepatitis B immunization status (vaccination Yes or No)
- HBsAg
- Anti-HBs antibody
- Anti-HBc antibody.
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All participants must have screening prior to enrollment; participants whose results indicate that they are carrier of hepatitis B can still be treated per group B and C but will NOT receive rituximab
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HIV test has been obtained within 42 days. Participants who test positive for HIV cannot be enrolled on therapeutic part of study, but are still eligible for biology studies.
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Informed consent must be obtained according to St. Jude guidelines before enrollment into study.
Participants from Collaborating Sites Participating in Biological Objectives Only:
- Participant must have a histologic diagnosis of a mature B cell lymphoma (e.g., Burkitt lymphoma/leukemia, atypical Burkitt lymphoma, diffuse large B-cell lymphoma, mediastinal large B-cell lymphoma, mature B-cell lymphoma NOS) as defined in the WHO classification.
- Participant must be < 22 years of age at the time of diagnosis.
- Participant must be previously untreated (no more than 72 hours of steroids, one intrathecal chemotherapy treatment, and/or emergency radiation) at the time of the diagnostic biopsy.
- Informed consent must be obtained by local PI or his/her designee according to ICH/Good Clinical Practice and local guidelines before enrollment into study.
Exclusion Criteria:
Participants from Collaborating Sites Participating in Therapeutic and Biological Objectives:
- Participants known to be HIV positive (for therapeutic part of protocol, HIV participants are eligible for biology studies).
- Participants who are pregnant or lactating.
- Inability or unwillingness of research participant or legal guardian to consent.
Participants from Collaborating Sites Participating in Biological Objectives Only:
- Inability or unwillingness of research participant or legal guardian to consent.
- Histologic diagnosis other than a mature B-cell lymphoma as defined in the WHO classification.
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 |
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Otro: Group A
Completely resected stage I or completely resected abdominal stage II lesions. Group A will include: COPAD x 2 cycles. |
Vincristine Prednis(ol)one, Cyclophosphamide, Doxorubicin, G-CSF In the event the patient cannot receive G-CSF, Pegfilgrastim can be substituted.
Otros nombres:
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Otro: Group B
All cases not eligible for Group A or Group C. (Murphy Stage III and non-CNS Stage IV) Group B will include the intervention COP, COPD M3, CYM as follows: Pre-Phase: COP Induction: COPAD M3 x 2 cycles Consolidation: CYM x 2 cycles. |
GROUP B Treatment Details Intravenous fluids should be given at a rate of 3000 mL/m2/day. Use of rasburicase may preclude the need for HCO3 Pre-Phase: Cyclophosphamide, Vincristine, Prednis(ol)one, IT medications Induction (2 cycles): Vincristine, Prednis(ol)one, Methotrexate, Leucovorin, Cyclophosphamide, Doxorubicin, IT medications, G-CSF, Rituximab Consolidation (2 cycles): Methotrexate, Leucovorin, Cytarabine, IT medications, G-CSF, Rituximab In the event the patient cannot receive G-CSF, Pegfilgrastim can be substituted.
Otros nombres:
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Otro: Group C
Any CNS involvement and/or bone marrow involvement ≥ 25% blasts. For CNS involvement one or more of the following applies:
Group C will include the intervention COP, COPADM8, CYVE as follows: Pre-Phase: COP Induction: COPADM8 cycle 1 Induction: COPADM8 Cycle 2 Consolidation: CYVE x 2 cycles and Maintenance |
Treatment: Intravenous fluids should be given at a rate of 3000 mL/m2/day. Use of rasburicase may preclude the need for HCO3. COP Pre-Phase: Cyclophosphamide, Vincristine, Prednis(ol)one, IT medications, Leucovorin. COPADM8 Induction (2 cycles): Vincristine, Prednis(ol)one, Methotrexate, Leucovorin, Cyclophosphamide, Doxorubicin, Rituximab, IT medications, G-CSF CYVE Consolidation (2 cycles): Cytarabine, High-Dose Ara-C, Etoposide, Rituximab, G-CSF. Maintenance No.1: Vincristine, Prednis(ol)one, Cyclophosphamide, Methotrexate, Leucovorin, Doxorubicin, IT medications, G-CSF. Maintenance No.2: Cytarabine, Etoposide, G-CSF, IT Medications. Maintenance No.3: Vincristine, Prednis(ol)one, Cyclophosphamide, Doxorubicin, G-CSF, IT Medications. Maintenance No. 4: Cytarabine, Etoposide, G-CSF, IT Medications. In the event the patient cannot receive G-CSF, Pegfilgrastim can be substituted.
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Gene Differential Expression Profiling of Burkitt Lymphoma (BL) vs. Non-BL in the US and Other Selected Geographic Regions of the World
Periodo de tiempo: 1 year after the participant is enrolled
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Gene expression levels in BL vs. non-BL will be analyzed through approximately 22,000 probesets on the Affymetrix U133A GeneChip by using two-factor analysis of variance model for each gene. |
1 year after the participant is enrolled
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Catalog and Estimate Frequencies of Copy Number Variations in Childhood Lymphomas
Periodo de tiempo: 1 year after the participant is enrolled
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The prevalence of CNVs between different subtypes of childhood lymphomas and geographic regions will be reported and compared with exact chi-square or Fisher's test. The CNVs are derived from Affymetrix SNP arrays. |
1 year after the participant is enrolled
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Integrated Analysis of CNVs and Gene Expressions in the US and Other Selected Geographic Regions of the World
Periodo de tiempo: 1 year after the participant is enrolled
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The association between the identified CNVs and gene expressions in the study cohort will be examined by using general linear models, and multiple tests will be considered. Gene expressions are measured by Affymetrix U133A arrays and CNVs are derived from Affymetrix SNP arrays. |
1 year after the participant is enrolled
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Pattern and Frequency of XLP Gene Mutations Presenting With B-cell Lymphomas in the United States and Selected Geographic Regions
Periodo de tiempo: 1 year after the participant enrollment
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Frequency of XLP mutation among boys will be calculated in each geographical region as well as in all regions pooled. The frequency is reported here as the number of boys with XLP gene mutations found in B-cell lymphomas boys. |
1 year after the participant enrollment
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Frequency of EBV Protein Expression (e.g., EBNA 3) in EBV-positive Lymphomas
Periodo de tiempo: 1 year after the participant is enrolled
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Frequency of EBV-positive BL will be calculated for each geographical region. |
1 year after the participant is enrolled
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Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Overall Survival
Periodo de tiempo: Up to 5 years after completion of therapy
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Overall survival (OS) will be estimated among eligible patients treated at SJCRH by the Kaplan-Meier estimator. |
Up to 5 years after completion of therapy
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Event-free Survival
Periodo de tiempo: Up to 5 years after completion of therapy
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Event-free survival (EFS) will be estimated among eligible patients treated at SJCRH by the Kaplan-Meier estimator. The events will include: (1) death while in continuous CR, (2) relapse, (3) secondary malignancy, and (4) failure to achieve complete response (CR). |
Up to 5 years after completion of therapy
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Complete Response Rate
Periodo de tiempo: Up to 5 years after completion of therapy
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Complete response rate will be estimated with exact 95% CI based on the binomial distribution, and it will be reported as the percentage of patients who reached complete remission among eligible patients treated at SJCRH |
Up to 5 years after completion of therapy
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Raul Ribeiro, MD, St. Jude Children's Research Hospital
Publicaciones y enlaces útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimado)
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
Términos MeSH relevantes adicionales
- Neoplasias
- Enfermedades del sistema inmunológico
- Neoplasias por tipo histológico
- Enfermedades hematológicas
- Enfermedades linfáticas
- Trastornos linfoproliferativos
- Trastornos inmunoproliferativos
- Enfermedades hemic y linfáticas
- Leucemia
- Linfoma
- Linfoma No Hodgkin
- Péptidos
- Aminoácidos, péptidos y proteínas
- Proteínas
- Químicos orgánicos
- Compuestos heterocíclicos, 1 anillo
- Compuestos heterocíclicos
- Compuestos heterocíclicos, 2 anillos
- Compuestos heterocíclicos, anillo fusionado
- Ácidos nucleicos, nucleótidos y nucleósidos
- Hidrocarburos
- Hidrocarburos, cíclico
- Factores biológicos
- Carbohidratos
- Podoflotoxina
- Tetrahidronaftalenos
- Naftalenos
- Hidrocarburos aromáticos policíclicos
- Hidrocarburos, aromáticos
- Compuestos policíclicos
- Glucósidos
- Glucósidos
- Enzimas y coenzimas
- Anticuerpos, monoclonal
- Anticuerpos
- Inmunoglobulinas
- Inmunoproteínas
- Proteínas de la sangre
- Globulinas séricas
- Globulinas
- Citidina
- Nucleósidos de pirimidina
- Pirimidinas
- Espierra
- Embarazos
- Esteroides
- Compuestos de anillo fusionado
- Mostaza de fosforamida
- Compuestos de mostaza de nitrógeno
- Compuestos de mostaza
- Hidrocarburos, halogenados
- Fosforamidas
- Compuestos organofosforados
- Nucleósidos
- Formiltetrahidrofolatos
- Tetrahidrofolatos
- Ácido fólico
- Pterins
- Pteridinas
- Péptidos de señalización intercelular y proteínas
- Madreadiediols
- Arabinonucleósidos
- Antraciclinas
- Naftacenos
- Aminoglucósidos
- Coenzimas
- Glicoproteínas
- Glucoconjugados
- Anticuerpos, monoclonales, derivados de murino
- Daunorrubicina
- Factores estimulantes de colonias
- Factores de crecimiento de células hematopoyéticas
- Citocinas
- Factor estimulador de colonias de granulocitos
- Rituximab
- Prednisona
- Ciclofosfamida
- Citarabina
- Etopósido
- Leucovorina
- Doxorrubicina
- Filgrastim
- pegfilgrastim
- rasburicasa
Otros números de identificación del estudio
- SJBC3
- NCI-2011-01251 (Identificador de registro: NCI Clinical Trial Registration Program)
Información sobre medicamentos y dispositivos, documentos del estudio
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Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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