Combination Chemotherapy, Monoclonal Antibody, and Radiation Therapy in Treating Patients With Primary Central Nervous System Lymphoma
1 de fevereiro de 2018 atualizado por: Radiation Therapy Oncology Group
Phase I/II Study Of Pre-Irradiation Chemotherapy With Methotrexate, Rituximab, And Temozolomide And Post -Irradiation Temozolomide For Primary Central Nervous System Lymphoma
RATIONALE: Drugs used in chemotherapy such as methotrexate and temozolomide use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Radiation therapy uses high-energy x-rays to damage cancer cells. Combining methotrexate, temozolomide, and rituximab with radiation therapy may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of temozolomide when given together with methotrexate and rituximab followed by radiation therapy and to see how well they work in treating patients with primary central nervous system lymphoma.
Visão geral do estudo
Status
Concluído
Descrição detalhada
OBJECTIVES:
- To assess the maximum tolerated dose (MTD) of temozolomide (TMZ) in combination with methotrexate (MTX) and rituximab (RTX) when administered prior to twice daily fractionated whole brain radiation therapy (WBRT) in patients with primary central nervous system lymphoma.
- To compare the two-year survival rate in patients receiving pre-irradiation chemotherapy, twice daily fractionated whole brain radiation therapy and post-irradiation temozolomide to the reported two-year survival rate of Radiation Therapy Oncology Group (RTOG) trial 93-10. RTOG 9310 does not fall within ClinicalTrials.gov registration/reporting requirements.)
- To compare the pre-irradiation chemotherapy tumor response rates to the reported rate from RTOG 93-10.
- To report progression-free survival.
- To assess acute and long-term neurologic toxicity, and to collect quality of life data for this patient group.
Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
Tipo de estudo
Intervencional
Inscrição (Real)
60
Estágio
- Fase 2
- Fase 1
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Locais de estudo
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Florida
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Jacksonville, Florida, Estados Unidos, 32207
- Baptist Cancer Institute - Jacksonville
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Jacksonville, Florida, Estados Unidos, 32207
- Integrated Community Oncology Network at Southside Cancer Center
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Jacksonville, Florida, Estados Unidos, 32258
- Baptist Medical Center South
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Jacksonville Beach, Florida, Estados Unidos, 32250
- Integrated Community Oncology Network
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Orange Park, Florida, Estados Unidos, 32073
- Integrated Community Oncology Network - Orange Park
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Palatka, Florida, Estados Unidos, 32177
- Florida Cancer Center - Palatka
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Saint Augustine, Florida, Estados Unidos, 32086
- Flagler Cancer Center
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Michigan
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Kalamazoo, Michigan, Estados Unidos, 49007
- Bronson Methodist Hospital
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Kalamazoo, Michigan, Estados Unidos, 49001
- Borgess Medical Center
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Kalamazoo, Michigan, Estados Unidos, 49007-3731
- West Michigan Cancer Center
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Missouri
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Kansas City, Missouri, Estados Unidos, 64131
- CCOP - Kansas City
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Saint Louis, Missouri, Estados Unidos, 63110
- Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
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Nevada
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Las Vegas, Nevada, Estados Unidos, 89106
- CCOP - Nevada Cancer Research Foundation
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New Jersey
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Edison, New Jersey, Estados Unidos, 08818
- John F. Kennedy Medical Center
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Ohio
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Cleveland, Ohio, Estados Unidos, 44195
- Cleveland Clinic Taussig Cancer Center
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Oregon
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Milwaukie, Oregon, Estados Unidos, 97222
- Providence Milwaukie Hospital
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Portland, Oregon, Estados Unidos, 97213-2967
- Providence Cancer Center at Providence Portland Medical Center
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Portland, Oregon, Estados Unidos, 97225
- CCOP - Columbia River Oncology Program
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Portland, Oregon, Estados Unidos, 97225
- Providence St. Vincent Medical Center
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Pennsylvania
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Philadelphia, Pennsylvania, Estados Unidos, 19107-5541
- Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
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South Carolina
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Charleston, South Carolina, Estados Unidos, 29425
- Hollings Cancer Center at Medical University of South Carolina
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Utah
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Murray, Utah, Estados Unidos, 84157
- Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
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Provo, Utah, Estados Unidos, 84604
- Utah Valley Regional Medical Center - Provo
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Washington
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Vancouver, Washington, Estados Unidos, 98668
- Southwest Washington Medical Center Cancer Center
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Wisconsin
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Menomonee Falls, Wisconsin, Estados Unidos, 53051
- Community Memorial Hospital Cancer Care Center
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Milwaukee, Wisconsin, Estados Unidos, 53226
- Medical College of Wisconsin Cancer Center
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Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
18 anos e mais velhos (Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
Inclusion criteria:
- Primary central nervous system (CNS) lymphoma [B-cell, Cluster of Differentiation 20 (CD20) antigen positive] based on positive biopsy or cerebrospinal fluid (CSF) or vitreous cytology (in association with measurable intraparenchymal tumor). Cytology must demonstrate lymphoma or have an immunohistochemical diagnosis of malignant lymphocytes with a monoclonal lymphocytic population.
- Life expectancy ≥ 8 weeks;
- Zubrod performance status of 0-2;
- Absolute granulocyte count ≥1500/mm3; platelet count ≥ 100,000/mm3; creatinine clearance ≥ 50, calculated with the Cockcroft-Gault Equation: Cr Clearance = (140-age) x wt (kg)/(Cr[mg/dl]x 72); Bilirubin, serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (AST) ≤ 2 x institutional upper limits of normal;
- Patients must sign a study-specific informed consent prior to study entry.
- Age ≥ 18
Exclusion criteria:
- Evidence of systemic lymphoma;
- Prior malignancy (excluding in situ carcinoma of the cervix or non-melanomatous skin cancer)unless disease free for at least five years;
- Prior radiotherapy to the brain or head/neck;
- Prior chemotherapy;
- History of idiopathic sensitivity to any of the drugs to be used;
- Active infectious process;
- Seropositive for HIV, AIDS, or post-organ transplant;
- Pregnant women are ineligible as treatment involves unforeseeable risks to the participant and to the embryo or fetus.
- Active hepatitis B.
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Não randomizado
- Modelo Intervencional: Atribuição sequencial
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: Phase I: Temozolomide 100 mg
Rituximab, methotrexate, temozolomide 100 mg/m^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m^2.
|
375 mg/m2, intravenously three days prior to the first cycle of methotrexate
Five cycles of methotrexate (MTX) at 3.5 gm/m2 administered every two weeks on weeks 1, 3, 5, 7, and 9 via intravenous infusion over four hours once per cycle.
Calcium leucovorin 25 mg orally or intravenously every six hours initiated exactly 24 hours following the start of the MTX infusion.
Methotrexate levels to be monitored daily, and calcium leucovorin discontinued when the MTX level is less than 10 micromolar.
Temozolomide 100 mg/m^2 by mouth per day for five days on weeks 4 and 8.
Whole brain irradiation (WBRT) during weeks 11, 12, and 13, five days per week (excluding weekends).
A daily dose of 2.4 Gy delivered in two fractions of 1.2 Gy each with a minimum inter-fraction interval of 6 hours, with a total dose to brain and meninges of 36 Gy.
Outros nomes:
Temozolomide (TMZ) 200 mg/m^2 by mouth per day for 5 days on weeks 14, 18, 22, 26, 30, 34, 38, 42, 46, and 50 for a total of 10 cycles.
|
|
Experimental: Phase I: Temozolomide 150 mg
Rituximab, methotrexate, temozolomide 150 mg/m^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m^2.
|
375 mg/m2, intravenously three days prior to the first cycle of methotrexate
Five cycles of methotrexate (MTX) at 3.5 gm/m2 administered every two weeks on weeks 1, 3, 5, 7, and 9 via intravenous infusion over four hours once per cycle.
Calcium leucovorin 25 mg orally or intravenously every six hours initiated exactly 24 hours following the start of the MTX infusion.
Methotrexate levels to be monitored daily, and calcium leucovorin discontinued when the MTX level is less than 10 micromolar.
Whole brain irradiation (WBRT) during weeks 11, 12, and 13, five days per week (excluding weekends).
A daily dose of 2.4 Gy delivered in two fractions of 1.2 Gy each with a minimum inter-fraction interval of 6 hours, with a total dose to brain and meninges of 36 Gy.
Outros nomes:
Temozolomide (TMZ) 200 mg/m^2 by mouth per day for 5 days on weeks 14, 18, 22, 26, 30, 34, 38, 42, 46, and 50 for a total of 10 cycles.
Temozolomide 150 mg/m^2 by mouth per day for five days on weeks 4 and 8.
|
|
Experimental: Phase I: Temozolomide 200 mg
Rituximab, methotrexate, temozolomide 200 mg/m^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m^2.
|
375 mg/m2, intravenously three days prior to the first cycle of methotrexate
Five cycles of methotrexate (MTX) at 3.5 gm/m2 administered every two weeks on weeks 1, 3, 5, 7, and 9 via intravenous infusion over four hours once per cycle.
Calcium leucovorin 25 mg orally or intravenously every six hours initiated exactly 24 hours following the start of the MTX infusion.
Methotrexate levels to be monitored daily, and calcium leucovorin discontinued when the MTX level is less than 10 micromolar.
Whole brain irradiation (WBRT) during weeks 11, 12, and 13, five days per week (excluding weekends).
A daily dose of 2.4 Gy delivered in two fractions of 1.2 Gy each with a minimum inter-fraction interval of 6 hours, with a total dose to brain and meninges of 36 Gy.
Outros nomes:
Temozolomide (TMZ) 200 mg/m^2 by mouth per day for 5 days on weeks 14, 18, 22, 26, 30, 34, 38, 42, 46, and 50 for a total of 10 cycles.
Temozolomide 200 mg/m^2 per day by mouth for five days on weeks 4 and 8.
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Experimental: Phase II: Temozolomide 100 mg
Rituximab, methotrexate, temozolomide 100 mg/m^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m^2.
|
375 mg/m2, intravenously three days prior to the first cycle of methotrexate
Five cycles of methotrexate (MTX) at 3.5 gm/m2 administered every two weeks on weeks 1, 3, 5, 7, and 9 via intravenous infusion over four hours once per cycle.
Calcium leucovorin 25 mg orally or intravenously every six hours initiated exactly 24 hours following the start of the MTX infusion.
Methotrexate levels to be monitored daily, and calcium leucovorin discontinued when the MTX level is less than 10 micromolar.
Temozolomide 100 mg/m^2 by mouth per day for five days on weeks 4 and 8.
Whole brain irradiation (WBRT) during weeks 11, 12, and 13, five days per week (excluding weekends).
A daily dose of 2.4 Gy delivered in two fractions of 1.2 Gy each with a minimum inter-fraction interval of 6 hours, with a total dose to brain and meninges of 36 Gy.
Outros nomes:
Temozolomide (TMZ) 200 mg/m^2 by mouth per day for 5 days on weeks 14, 18, 22, 26, 30, 34, 38, 42, 46, and 50 for a total of 10 cycles.
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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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Number of Phase I Participants Experiencing Toxicity
Prazo: From start of treatment to 10 weeks if radiation therapy received, to 15 weeks if not.
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A dose limiting toxicity (DLT) is defined as any grade 3 or 4 non-hematological toxicity (other than grade 3 nausea/vomiting) or any hematological toxicity resulting in the discontinuation of temozolomide.
Toxicity evaluation for this dose escalation includes all toxicities occurring prior to the start of radiation therapy.
If the patient did not receive radiation therapy, then toxicity evaluation included all toxicities occurring through week 15.
Any grade 5 toxicity would result in immediate suspension of accrual.
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From start of treatment to 10 weeks if radiation therapy received, to 15 weeks if not.
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Phase II: Overall Survival Rate at 2 Years (Including Phase I Patients at Same Dose)
Prazo: Analysis occured after all patients have been on study for 2 years. Maximum follow-up at time of analysis was 8.5 years.
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Survival time is defined as time from registration to date of death from any cause and is estimated by the Kaplan-Meier method.
Patients last known to be alive are censored at the date of last contact.
(Please note that this outcome measure is considered the primary endpoint for the Phase II component of the study, but that the patients from Phase I that were treated at the same dose level are included, as indicated in the treatment arm descriptions.
)
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Analysis occured after all patients have been on study for 2 years. Maximum follow-up at time of analysis was 8.5 years.
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Phase II: Pre-irradiation Chemotherapy Tumor Response Rate (Including Phase I Patients at Same Dose)
Prazo: From start of treatment to 10 weeks if RT received, to 15 weeks if not.
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Tumor response was centrally reviewed.
Complete response: Disappearance of all enhancing tumor, the patient must be off steroid therapy and neurologically stable or improved; partial response: ≥ 50% decrease in enhancing tumor; progressive disease: ≥ 25% increase in a lesion, progressive or newly emergent meningeal or ocular disease.
(Please note that this outcome measure is considered a secondary endpoint for the Phase II component of the study, but that the patients from Phase I that were treated at the same dose level are included, as indicated in the treatment arm descriptions.
)
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From start of treatment to 10 weeks if RT received, to 15 weeks if not.
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Phase II: Progression-free Survival (Including Phase I Patients at Same Dose)
Prazo: Analysis occured after all patients have been on study for 2 years. Maximum follow-up at time of analysis was 8.5 years.
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Progression is defined as greater than 25% increase in enhancing tumor or the appearance of new lesions in the brain, eye, or the appearance of a new positive cerebrospinal fluid (CSF) cytology.
The patient may be neurologically stable or worse and on stable or increasing doses of corticosteroid.
Progression-free survival time is defined as time from registration to the date of progression, death, or last known follow-up (censored).
Progression-free survival rates are estimated using the Kaplan-Meier method.
(Please note that this outcome measure is considered a secondary endpoint for the Phase II component of the study, but that the patients from Phase I that were treated at the same dose level are included, as indicated in the treatment arm descriptions.
)
|
Analysis occured after all patients have been on study for 2 years. Maximum follow-up at time of analysis was 8.5 years.
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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Investigadores
- Cadeira de estudo: Jon Glass, MD, Sidney Kimmel Cancer Center at Thomas Jefferson University
Publicações e links úteis
A pessoa responsável por inserir informações sobre o estudo fornece voluntariamente essas publicações. Estes podem ser sobre qualquer coisa relacionada ao estudo.
Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo
1 de julho de 2003
Conclusão Primária (Real)
1 de dezembro de 2016
Conclusão do estudo (Real)
1 de dezembro de 2016
Datas de inscrição no estudo
Enviado pela primeira vez
10 de setembro de 2003
Enviado pela primeira vez que atendeu aos critérios de CQ
10 de setembro de 2003
Primeira postagem (Estimativa)
11 de setembro de 2003
Atualizações de registro de estudo
Última Atualização Postada (Real)
7 de fevereiro de 2018
Última atualização enviada que atendeu aos critérios de controle de qualidade
1 de fevereiro de 2018
Última verificação
1 de fevereiro de 2018
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Doenças do Sistema Nervoso
- Doenças do sistema imunológico
- Neoplasias por Tipo Histológico
- Neoplasias
- Distúrbios Linfoproliferativos
- Doenças Linfáticas
- Distúrbios imunoproliferativos
- Neoplasias por local
- Linfoma
- Neoplasias do Sistema Nervoso
- Neoplasias do Sistema Nervoso Central
- Efeitos Fisiológicos das Drogas
- Mecanismos Moleculares de Ação Farmacológica
- Inibidores da Síntese de Ácido Nucleico
- Inibidores Enzimáticos
- Agentes Antirreumáticos
- Antimetabólitos, Antineoplásicos
- Antimetabólitos
- Agentes Antineoplásicos
- Agentes imunossupressores
- Fatores imunológicos
- Agentes Antineoplásicos Alquilantes
- Agentes Alquilantes
- Agentes Antineoplásicos Imunológicos
- Agentes dermatológicos
- Agentes de Controle Reprodutivo
- Agentes abortivos, não esteróides
- Agentes abortivos
- Antagonistas do ácido fólico
- Temozolomida
- Rituximabe
- Metotrexato
Outros números de identificação do estudo
- RTOG-0227
- CDR0000301563
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .