Rituximab and Combination Chemotherapy in Treating Patients With Newly Diagnosed Primary CNS Lymphoma
Intensive Chemotherapy And Immunotherapy In Patients With Newly Diagnosed Primary CNS Lymphoma
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving rituximab with combination chemotherapy may kill more cancer cells.
PURPOSE: This phase II trial is studying how well rituximab given with combination chemotherapy works in treating patients with newly diagnosed primary CNS lymphoma.
Visão geral do estudo
Status
Condições
Descrição detalhada
OBJECTIVES:
Primary
- Determine the complete response rate after remission induction therapy with the combination of high-dose methotrexate (HDMTX), temozolomide, and rituximab at 4 months.
Secondary
- Determine the safety and feasibility of consolidation therapy comprising cytarabine and etoposide administered after induction therapy in these patients.
- Determine the percentage of patients who achieve durable (complete and partial) remission when treated with this regimen.
- Determine relapse-free survival after complete response in patients treated with this regimen.
- Correlate molecular markers with outcome in patients treated with this regimen.
- Determine the effects of this regimen on neurological function in these patients.
OUTLINE: This is a multicenter study.
Induction Chemotherapy: All induction therapy courses repeat every 28 days.
- Courses 1-3: Patients receive high-dose methotrexate IV over 4 hours on days 1 and 15, leucovorin calcium IV or orally every 6 hours beginning on days 2 and 16 and continuing until blood levels of methotrexate are in a safe range, and oral temozolomide on days 7-11. Patients also receive rituximab* IV on days 3, 10, 17, and 24 of course 1 and days 3 and 10 of course 2 (total of 6 doses).
NOTE: *Patients diagnosed with T-cell primary CNS lymphoma do not receive rituximab.
Course 4: Patients receive oral temozolomide on days 7-11, high-dose methotrexate IV over 4 hours on day 15, and leucovorin calcium IV or orally every 6 hours beginning on day 16 and continuing until blood levels of methotrexate are in a safe range. Patients achieving a complete response or a complete response unconfirmed proceed to consolidation therapy.
- Consolidation therapy I (course 5): Beginning 4 weeks after the start of course 4, patients receive high-dose methotrexate IV over 4 hours on day 1, leucovorin calcium IV or orally every 6 hours beginning on day 2 and continuing until blood levels of methotrexate are in a safe range, and oral temozolomide on days 7-11.
- Consolidation therapy II (course 6): Beginning 3-5 weeks after the start of course 5, patients receive cytarabine IV over 2 hours twice daily and etoposide IV over 12 hours twice daily on days 1-4 and filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously beginning on day 14 and continuing until blood counts recover.
Treatment continues in the absence of disease progression.
After completion of study treatment, patients are followed periodically for 3 years.
PROJECTED ACCRUAL: A total of 27-45 patients will be accrued for this study within 2-3 years.
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 2
Contactos e Locais
Locais de estudo
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California
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San Francisco, California, Estados Unidos, 94115
- UCSF Helen Diller Family Comprehensive Cancer Center
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Delaware
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Lewes, Delaware, Estados Unidos, 19958
- Tunnell Cancer Center at Beebe Medical Center
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Newark, Delaware, Estados Unidos, 19713
- CCOP - Christiana Care Health Services
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Illinois
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Chicago, Illinois, Estados Unidos, 60637-1470
- University of Chicago Cancer Research Center
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Indiana
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Fort Wayne, Indiana, Estados Unidos, 46845
- Fort Wayne Medical Oncology and Hematology
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Iowa
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Bettendorf, Iowa, Estados Unidos, 52722
- Hematology Oncology Associates of the Quad Cities
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Kansas
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Overland Park, Kansas, Estados Unidos, 66209
- Menorah Medical Center
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Overland Park, Kansas, Estados Unidos, 66213
- Saint Luke's Hospital - South
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Shawnee Mission, Kansas, Estados Unidos, 66204
- Shawnee Mission Medical Center
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Maryland
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Elkton MD, Maryland, Estados Unidos, 21921
- Union Hospital Cancer Program at Union Hospital
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Minnesota
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Minneapolis, Minnesota, Estados Unidos, 55455
- Masonic Cancer Center at University of Minnesota
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Missouri
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Kansas City, Missouri, Estados Unidos, 64131
- CCOP - Kansas City
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Kansas City, Missouri, Estados Unidos, 64116
- North Kansas City Hospital
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Kansas City, Missouri, Estados Unidos, 64132
- Research Medical Center
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Kansas City, Missouri, Estados Unidos, 64108
- Truman Medical Center - Hospital Hill
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Kansas City, Missouri, Estados Unidos, 64111
- Saint Luke's Cancer Institute at Saint Luke's Hospital
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Kansas City, Missouri, Estados Unidos, 64114
- St. Joseph Medical Center
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Kansas City, Missouri, Estados Unidos, 64116
- Parvin Radiation Oncology
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Lee's Summit, Missouri, Estados Unidos, 64086
- Saint Luke's East - Lee's Summit
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Liberty, Missouri, Estados Unidos, 64068
- Liberty Hospital
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Saint Joseph, Missouri, Estados Unidos, 64506
- Heartland Regional Medical Center
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New Jersey
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Voorhees, New Jersey, Estados Unidos, 08043
- Cancer Institute of New Jersey at Cooper - Voorhees
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New York
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Stony Brook, New York, Estados Unidos, 11794-9446
- Stony Brook University Cancer Center
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Syracuse, New York, Estados Unidos, 13210
- SUNY Upstate Medical University Hospital
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Ohio
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Columbus, Ohio, Estados Unidos, 43210-1240
- Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
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Rhode Island
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Providence, Rhode Island, Estados Unidos, 02906
- Miriam Hospital
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Providence, Rhode Island, Estados Unidos, 02903
- Rhode Island Hospital Comprehensive Cancer Center
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Vermont
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Berlin, Vermont, Estados Unidos, 05602
- Mountainview Medical
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Burlington, Vermont, Estados Unidos, 05401
- Fletcher Allen Health Care - University Health Center Campus
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Virginia
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Danville, Virginia, Estados Unidos, 24541
- Danville Regional Medical Center
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Filho
- Adulto
- Adulto mais velho
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
DISEASE CHARACTERISTICS:
Histologically confirmed newly diagnosed primary CNS lymphoma confirmed by 1 of the following methods:
- Brain biopsy or resection
Cerebrospinal fluid (CSF) cytology
- Positive CSF cytology with or without measurable intracranial disease
No evidence of systemic non-Hodgkin's lymphoma
- CT scan or MRI of the chest, abdomen, and pelvis AND bilateral bone marrow biopsy or unilateral biopsy with a 2cm core biopsy specimen that is negative for extracerebral source of lymphoma
- Measurable contrast-enhancing disease by MRI of the brain and spine (plus gadolinium) unless CSF cytology positive
- No evidence of pleural effusions or ascites
PATIENT CHARACTERISTICS:
Age
- Any age
Performance status
- ECOG 0-2
Life expectancy
- Not specified
Hematopoietic
- Absolute neutrophil count ≥ 1,500/mm^3
Hepatic
- ALT and AST ≤ 2 times upper limit of normal
- Bilirubin ≤ 2 mg/dL
Renal
- Creatinine clearance ≥ 50 mL/min
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for at least 6 months after study participation
- HIV negative
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- Not specified
Endocrine therapy
- Concurrent steroids for the management of symptoms related to lymphoma allowed
Radiotherapy
- No concurrent palliative radiotherapy
Surgery
- Not specified
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: N / D
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Experimental: Intensive Combination Chemo & Immunotherapy
Induction Cycles 1-3: Methotrexate 8gm/m^2 days 1 & 15; Leucovorin 100 mg/m^2 days 2 & 16; Rituximab 375 mg/m^2 days 3, 10, 17 & 24 of cycle 1, days 3 & 10 of cycle 2; Temozolomide 150 mg/m^2/day PO days 7-11 Induction Cycle 4: Temozolomide 150 mg/m^2/day PO days 7-11; Methotrexate 8gm/m^2 day 15; Leucovorin 100 mg/m^2 day 16 Consolidation Cycle 5: Methotrexate 8gm/m^2 days 1; Leucovorin 100 mg/m^2 days 2; Temozolomide 150 mg/m^2/day PO days 7-11 Consolidation Cycle 6: Cytarabine 2 g/m^2 (x 8 doses) days 1-4; Etoposide 5 mg/kg (x 8 doses) days 1-4; G-CSF 5 mcg/kg/day or GM-CSF 250 mcg/m^2/day starting day 14 until ANC recovers (>= 500 for 2 consecutive days or >= 1500 for one day) |
5 mcg/kg subQ injection daily Day 14 until ANC > or = 500 uL for 2 days or 1500 uL for 1 day (Cycle 6)
Outros nomes:
375 mg/sq m IV infusion (max rate of 400 mg/hr) on Days 3, 10, 17, & 24 of Cycle 1 nad Days 3 & 10 of Cycle 2
2 g/sq m IV infusion over 2 hours q 12 hrs x 8 doses Days 1-4 of Cycle 6
5 mg/kg IV infusion over 12 hrs q 12 hrs x 8 doses Days 1-4 of Cycle 6
100 mg/sq m IV infusion q 6 hrs starting 24 hrs after ea MTX dose until serum MTX < or = 0.05uM Cycles 1-5.
8 g/sq m IV infusion over 4 hrs Days 1 & 15 Cycles 1, 2, & 3; Day 15 Cycle 4 and Day 1 Cycle 5.
150 mg/sq m PO Days 7-11 Cycles 1-5.
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Complete Response Rate After Remission Induction
Prazo: 4 months
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Response is assessed by investigator according to Revised Response Criteria for Malignant Lymphoma.
Complete response requires disappearance of all evidence of disease.
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4 months
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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4 Year Progression Free Rate
Prazo: 4 years
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Percentage of patients who were progression free at 4 years. The 4-year progression free rate was estimated using the Kaplan Meier method. Relapse was assessed by investigator according to Revised Response Criteria for Malignant Lymphoma. Progression required a 25% increase of previous area of gadolinium enhancement, appearance of new areas of T1 gadolinium enhancement or new appearance of malignant cells in the spinal fluid or new tumor appearance in other sites of the body |
4 years
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Change From Baseline in Mini-Mental Status Evaluation at 4 Months
Prazo: Baseline & month 4
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Neurologic functioning will be assessed using the Mini-Mental Status Evaluation (MMSE), a standardized, bedside tool for evaluation of higher mental function.
This assessment is based on a 30-point scale (0-30) with higher scores associated with better performance.
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Baseline & month 4
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4 Year Overall Survival Rate
Prazo: 4 years
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Percentage of patients who were alive at 4 years.
The 4-year survival rate was estimated using the Kaplan Meier method.
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4 years
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Cadeira de estudo: James Rubenstein, MD, PhD, University of California, San Francisco
Publicações e links úteis
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Doenças do sistema imunológico
- Neoplasias por Tipo Histológico
- Neoplasias
- Distúrbios Linfoproliferativos
- Doenças Linfáticas
- Distúrbios imunoproliferativos
- Linfoma
- Efeitos Fisiológicos das Drogas
- Mecanismos Moleculares de Ação Farmacológica
- Agentes Anti-Infecciosos
- Antivirais
- Inibidores da Síntese de Ácido Nucleico
- Inibidores Enzimáticos
- Agentes Antirreumáticos
- Antimetabólitos, Antineoplásicos
- Antimetabólitos
- Agentes Antineoplásicos
- Agentes imunossupressores
- Fatores imunológicos
- Agentes de proteção
- Agentes Antineoplásicos Alquilantes
- Agentes Alquilantes
- Agentes Antineoplásicos Fitogênicos
- Inibidores da Topoisomerase II
- Inibidores da Topoisomerase
- Agentes Antineoplásicos Imunológicos
- Agentes dermatológicos
- Micronutrientes
- Vitaminas
- Hormônios e Agentes Reguladores de Cálcio
- Agentes de Controle Reprodutivo
- Antídotos
- Complexo de Vitamina B
- Agentes abortivos, não esteróides
- Agentes abortivos
- Antagonistas do ácido fólico
- Etoposídeo
- Temozolomida
- Rituximabe
- Leucovorina
- Cálcio
- Levoleucovorina
- Citarabina
- Metotrexato
Outros números de identificação do estudo
- CALGB-50202
- U10CA031946 (Concessão/Contrato do NIH dos EUA)
- CDR0000398106 (Identificador de registro: NCI Physician Data Query)
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