Combination Chemotherapy in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome
Acute Myeloid Leukemia Salvage Therapy for Patients in First Relapse or Who Fail to Achieve an Initial Remission or Who Develop AML as a Second Malignant Neoplasm
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.
PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy in treating patients with acute myeloid leukemia or myelodysplastic syndrome in first relapse or who did not achieve first remission.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
- Medicamento: cloridrato de mitoxantrona
- Medicamento: cladribina
- Medicamento: citarabina
- Medicamento: etoposido
- Medicamento: metotrexato
- Medicamento: hidrocortisona terapêutica
- Procedimento: Transplante de Medula Óssea Alogênico
- Procedimento: transplante de células-tronco do sangue periférico
- Biológico: filgrastim
- Procedimento: transplante autólogo de medula óssea
- Radiação: eletroterapia de baixo LET
- Radiação: terapia de fótons de baixo LET
- Radiação: terapia de raios gama de cobalto-60 de baixo LET
Descrição detalhada
OBJECTIVES: I. Determine the toxicity, remission rate, event-free survival, and overall survival following induction with cytarabine/mitoxantrone (ARA-C/DHAD), intensification with ARA-C and etoposide (VP-16), and consolidation with cladribine (2-CdA) and VP-16 in patients with acute myeloid leukemia (AML) that is secondary, in first relapse, or has failed initial remission induction therapy. II. Compare the remission induction rate and event-free survival on this trial with prior second-line studies (i.e., protocols CCG-243, CCG-201, and CCG-261P). III. Compare survival of patients on this trial with the survival of patients relapsing or failing to achieve an initial complete remission (CR) on previous front-line AML trials (i.e., protocols CCG-251, CCG-213, CCG-2861, and CCG-2891). IV. Determine the frequency and prognostic significance of mdr1 gene expression and p53, topoisomerase II, and deoxycytidine kinase gene mutations in these patients. V. Determine the disease-free and overall survival of patients achieving a CR on this study in relation to the post-intensification therapy received (i.e., bone marrow transplantation, chemotherapy, or no further therapy). VI. Determine the frequency and degree of abnormal cardiac function on echocardiogram or MUGA at 1 and 5 years in patients treated with mitoxantrone following anthracycline therapy during initial treatment. VII. Provide a control arm evaluating the safety of using phase I or II agents in an "upfront window" approach planned for future CCG studies. VIII. Determine the toxicity, remission rate, event-free survival, and overall survival in patients who fail to achieve a CR with ARA-C/DHAD induction and are then treated with 2-CdA/VP-16. IX. Determine the biologic characteristics, toxicity, remission rate, event-free survival, and overall survival following this treatment regimen in patients who develop AML as a second malignancy.
OUTLINE: Patients who do not achieve M1/M2a marrow following Induction proceed to Salvage Induction; all others proceed to Intensification. Patients receive Consolidation therapy on Regimen A, B, or C according to the investigator's choice. The following acronyms are used: ARA-C Cytarabine, NSC-63878 2-CdA Cladribine (2-Chlorodeoxyadenosine), NSC-105014 DHAD Mitoxantrone, NSC-301739 G-CSF Filgrastim, NSC-614629 HC Hydrocortisone, NSC-10483 HD High Dose MTX Methotrexate, NSC-740 PBSC Peripheral Blood Stem Cells TBI Total-Body Irradiation TIT Triple Intrathecal Therapy (IT ARA-C/IT HC/IT MTX) VP-16 Etoposide, NSC-141540 INDUCTION: 2-Drug Combination Chemotherapy plus CNS Prophylaxis/Therapy. ARA-C/DHAD; G-CSF; plus IT ARA-C and, if CNS disease at entry, TIT. SALVAGE INDUCTION: 2-Drug Combination Chemotherapy. 2-CdA/VP-16. INTENSIFICATION: 2-Drug Combination Chemotherapy followed, as indicated, by Radiotherapy. HD ARA-C/VP-16; followed, in patients with persistent CNS disease, CNS relapse, or chloromas, by irradiation using megavoltage equipment (minimum Co60 and maximum 6 MV x-rays or electrons). CONSOLIDATION: Regimen A: 2-Drug Combination Chemotherapy. 2-CdA/VP-16. Regimen B: Myeloablative Chemoradiotherapy followed by Hematopoietic Rescue. TBI (equipment unspecified) with electron boosts to the testes, chest, extramedullary sites, and, if indicated, craniospinal region; VP-16; followed by allogeneic or autologous bone marrow or PBSC. Regimen C: No further therapy.
PROJECTED ACCRUAL: A total of 90 patients will be entered. The study may be closed if there are 7 or more deaths in the first 45 patients who complete Intensification.
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 2
Contactos e Locais
Locais de estudo
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Western Australia
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Perth, Western Australia, Austrália, 6001
- Princess Margaret Hospital for Children
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British Columbia
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Vancouver, British Columbia, Canadá, V6H 3V4
- British Columbia Children's Hospital
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Nova Scotia
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Halifax, Nova Scotia, Canadá, B3J 3G9
- IWK Grace Health Centre
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California
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Long Beach, California, Estados Unidos, 90806
- Long Beach Memorial Medical 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, 92668
- Children's Hospital of Orange County
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San Francisco, California, Estados Unidos, 94115-0128
- UCSF Cancer Center and Cancer Research Institute
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Colorado
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Denver, Colorado, Estados Unidos, 80218
- Children's Hospital of Denver
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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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Illinois
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Chicago, Illinois, Estados Unidos, 60637
- University of Chicago Cancer Research Center
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Indiana
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Indianapolis, Indiana, Estados Unidos, 46202-5265
- Indiana University Cancer Center
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Iowa
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Iowa City, Iowa, Estados Unidos, 52242
- University of Iowa Hospitals and Clinics
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Michigan
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Ann Arbor, Michigan, Estados Unidos, 48109-0752
- University Of Michigan Comprehensive Cancer Center
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Kalamazoo, Michigan, Estados Unidos, 49007-3731
- CCOP - Kalamazoo
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Minnesota
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Minneapolis, Minnesota, Estados Unidos, 55455
- University of Minnesota Cancer Center
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Rochester, Minnesota, Estados Unidos, 55905
- Mayo Clinic Cancer Center
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Missouri
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Kansas City, Missouri, Estados Unidos, 64108
- Children's Mercy Hospital - Kansas City
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Nebraska
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Omaha, Nebraska, Estados Unidos, 68198-3330
- University of Nebraska Medical Center
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New Jersey
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New Brunswick, New Jersey, Estados Unidos, 08901
- Cancer Institute Of New Jersey
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New York
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New York, New York, Estados Unidos, 10021
- Memorial Sloan-Kettering Cancer Center
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New York, New York, Estados Unidos, 10016
- Kaplan Cancer Center
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New York, New York, Estados Unidos, 10032
- Herbert Irving Comprehensive Cancer Center
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North Carolina
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Chapel Hill, North Carolina, Estados Unidos, 27599-7295
- Lineberger Comprehensive Cancer Center, UNC
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North Dakota
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Fargo, North Dakota, Estados Unidos, 58102
- Veterans Affairs Medical Center - Fargo
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Fargo, North Dakota, Estados Unidos, 58122
- CCOP - Merit Care Hospital
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Ohio
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Cincinnati, Ohio, Estados Unidos, 45229-3039
- Children's Hospital Medical Center - Cincinnati
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Cleveland, Ohio, Estados Unidos, 44106-5065
- Ireland Cancer Center
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Columbus, Ohio, Estados Unidos, 43205-2696
- Children's Hospital of Columbus
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Oregon
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Portland, Oregon, Estados Unidos, 97201-3098
- Doernbecher Children's Hospital
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Pennsylvania
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Philadelphia, Pennsylvania, Estados Unidos, 19104
- Children's Hospital of Philadelphia
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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, 37232-6838
- Vanderbilt Cancer Center
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Texas
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Houston, Texas, Estados Unidos, 77030
- University of Texas - MD Anderson Cancer Center
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Utah
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Salt Lake City, Utah, Estados Unidos, 84132
- Huntsman Cancer Institute
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Washington
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Seattle, Washington, Estados Unidos, 98109
- Fred Hutchinson Cancer Research Center
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Seattle, Washington, Estados Unidos, 98105
- Children's Hospital and Medical Center - Seattle
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Wisconsin
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Madison, Wisconsin, Estados Unidos, 53792
- University of Wisconsin Comprehensive Cancer Center
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
DISEASE CHARACTERISTICS: Acute myeloid leukemia (AML) or myelodysplastic syndrome in one of the following categories: In first relapse Failed to achieve initial complete remission Newly diagnosed secondary AML eligible Required bone marrow status: Greater than 25% blasts (M3) OR Persistent abnormal clone on cytogenetics and 5-25% blasts (M2) No Fanconi's anemia
PATIENT CHARACTERISTICS: Age: Under 22 Performance status: Not specified Hematopoietic: See Disease Characteristics Hepatic: Bilirubin no greater than 1.5 times normal AST or ALT less than 4.0 times normal Renal: Creatinine no greater than 1.5 times normal OR Creatinine clearance or GFR greater than 70 mL/min per 1.73 square meters or GFR in equivalent institutional normal range Cardiovascular: Shortening fraction greater than 27% by echocardiogram or in institutional normal range OR Ejection fraction greater than 47% by radionuclide angiogram
PRIOR CONCURRENT THERAPY: No more than 1 prior treatment No prior salvage therapy No prior mitoxantrone
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: Treatment
Induction will consist of one course of cytarabine and mitoxantrone.
Patients achieving a complete or partial response by the end of induction will start intensification.
Intensification will consist of one course of chemotherapy (Cytarabine (Ara-C), Etoposide (VP-16), Filgrastim (G-CSF)).
Patients who do not attain a CNS remission following the completion of intensification therapy, or who develop recurrence of CNS disease and have not previously received radiation therapy involving the central nervous system should receive craniospinal radiotherapy.
Continuation Therapy: cladribine (2CdA), Etoposide.
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Prazo |
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Estimate second remission rate and survival rate
Prazo: 3 years
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3 years
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
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Evaluate the mortality of the start of VP-16/Ara-C intensification
Prazo: 45 days
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45 days
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Compare outcomes by the ethnicity and gender
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Compare outcomes by the ethnicity (and gender) in study CCG-2951, and will control for ethnicity in multivariate models comparing the treatment arms
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Cadeira de estudo: Robert J. Wells, MD, Children's Hospital Medical Center, Cincinnati
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
- Neoplasias por Tipo Histológico
- Neoplasias
- Doenças da Medula Óssea
- Doenças Hematológicas
- Síndromes Mielodisplásicas
- Leucemia
- Leucemia Mieloide
- Leucemia Mieloide Aguda
- Efeitos Fisiológicos das Drogas
- Mecanismos Moleculares de Ação Farmacológica
- Agentes Anti-Infecciosos
- Agentes do Sistema Nervoso Periférico
- Antivirais
- Inibidores da Síntese de Ácido Nucleico
- Inibidores Enzimáticos
- Analgésicos
- Agentes do Sistema Sensorial
- Antiinflamatórios
- Agentes Antirreumáticos
- Antimetabólitos, Antineoplásicos
- Antimetabólitos
- Agentes Antineoplásicos
- Agentes imunossupressores
- Fatores imunológicos
- Agentes Antineoplásicos Fitogênicos
- Inibidores da Topoisomerase II
- Inibidores da Topoisomerase
- Agentes dermatológicos
- Vestigios
- Micronutrientes
- Agentes de Controle Reprodutivo
- Agentes abortivos, não esteróides
- Agentes abortivos
- Antagonistas do ácido fólico
- Etoposídeo
- Citarabina
- Metotrexato
- Mitoxantrona
- Cladribina
- Hidrocortisona
- Hidrocortisona 17-butirato 21-propionato
- Acetato de hidrocortisona
- Hemisuccinato de hidrocortisona
- Cobalto
Outros números de identificação do estudo
- 2951
- CCG-2951
- CDR0000064907 (Outro identificador: Clinical Trials.gov)
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