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.
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
- Droga: mitoxantrone cloridrato
- Droga: cladribina
- Droga: citarabina
- Droga: etoposide
- Droga: metotrexato
- Droga: idrocortisone terapeutico
- Procedura: trapianto allogenico di midollo osseo
- Procedura: trapianto di cellule staminali del sangue periferico
- Biologico: filgrastim
- Procedura: trapianto autologo di midollo osseo
- Radiazione: terapia con elettroni a basso LET
- Radiazione: fototerapia a basso LET
- Radiazione: terapia con raggi gamma cobalto-60 a basso LET
Descrizione dettagliata
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 di studio
Iscrizione (Effettivo)
Fase
- Fase 2
Contatti e Sedi
Luoghi di studio
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Western Australia
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Perth, Western Australia, Australia, 6001
- Princess Margaret Hospital for Children
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British Columbia
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Vancouver, British Columbia, Canada, V6H 3V4
- British Columbia Children's Hospital
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Nova Scotia
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Halifax, Nova Scotia, Canada, B3J 3G9
- IWK Grace Health Centre
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California
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Long Beach, California, Stati Uniti, 90806
- Long Beach Memorial Medical Center
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Los Angeles, California, Stati Uniti, 90095-1781
- Jonsson Comprehensive Cancer Center, UCLA
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Los Angeles, California, Stati Uniti, 90027-0700
- Children's Hospital Los Angeles
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Orange, California, Stati Uniti, 92668
- Children's Hospital of Orange County
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San Francisco, California, Stati Uniti, 94115-0128
- UCSF Cancer Center and Cancer Research Institute
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Colorado
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Denver, Colorado, Stati Uniti, 80218
- Children's Hospital of Denver
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District of Columbia
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Washington, District of Columbia, Stati Uniti, 20010-2970
- Children's National Medical Center
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Illinois
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Chicago, Illinois, Stati Uniti, 60637
- University of Chicago Cancer Research Center
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Indiana
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Indianapolis, Indiana, Stati Uniti, 46202-5265
- Indiana University Cancer Center
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Iowa
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Iowa City, Iowa, Stati Uniti, 52242
- University of Iowa Hospitals and Clinics
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Michigan
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Ann Arbor, Michigan, Stati Uniti, 48109-0752
- University of Michigan Comprehensive Cancer Center
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Kalamazoo, Michigan, Stati Uniti, 49007-3731
- CCOP - Kalamazoo
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Minnesota
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Minneapolis, Minnesota, Stati Uniti, 55455
- University of Minnesota Cancer Center
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Rochester, Minnesota, Stati Uniti, 55905
- Mayo Clinic Cancer Center
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Missouri
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Kansas City, Missouri, Stati Uniti, 64108
- Children's Mercy Hospital - Kansas City
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Nebraska
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Omaha, Nebraska, Stati Uniti, 68198-3330
- University of Nebraska Medical Center
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New Jersey
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New Brunswick, New Jersey, Stati Uniti, 08901
- Cancer Institute Of New Jersey
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New York
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New York, New York, Stati Uniti, 10021
- Memorial Sloan-Kettering Cancer Center
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New York, New York, Stati Uniti, 10016
- Kaplan Cancer Center
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New York, New York, Stati Uniti, 10032
- Herbert Irving Comprehensive Cancer Center
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North Carolina
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Chapel Hill, North Carolina, Stati Uniti, 27599-7295
- Lineberger Comprehensive Cancer Center, UNC
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North Dakota
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Fargo, North Dakota, Stati Uniti, 58102
- Veterans Affairs Medical Center - Fargo
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Fargo, North Dakota, Stati Uniti, 58122
- CCOP - Merit Care Hospital
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Ohio
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Cincinnati, Ohio, Stati Uniti, 45229-3039
- Children's Hospital Medical Center - Cincinnati
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Cleveland, Ohio, Stati Uniti, 44106-5065
- Ireland Cancer Center
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Columbus, Ohio, Stati Uniti, 43205-2696
- Children's Hospital of Columbus
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Oregon
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Portland, Oregon, Stati Uniti, 97201-3098
- Doernbecher Children's Hospital
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Pennsylvania
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Philadelphia, Pennsylvania, Stati Uniti, 19104
- Children's Hospital of Philadelphia
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Pittsburgh, Pennsylvania, Stati Uniti, 15213
- Children's Hospital of Pittsburgh
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Tennessee
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Nashville, Tennessee, Stati Uniti, 37232-6838
- Vanderbilt Cancer Center
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Texas
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Houston, Texas, Stati Uniti, 77030
- University of Texas - MD Anderson Cancer Center
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Utah
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Salt Lake City, Utah, Stati Uniti, 84132
- Huntsman Cancer Institute
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Washington
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Seattle, Washington, Stati Uniti, 98109
- Fred Hutchinson Cancer Research Center
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Seattle, Washington, Stati Uniti, 98105
- Children's Hospital and Medical Center - Seattle
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Wisconsin
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Madison, Wisconsin, Stati Uniti, 53792
- University of Wisconsin Comprehensive Cancer Center
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: N / A
- Modello interventistico: Assegnazione di gruppo singolo
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
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Sperimentale: 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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Altri nomi:
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Lasso di tempo |
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Estimate second remission rate and survival rate
Lasso di tempo: 3 years
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3 years
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Evaluate the mortality of the start of VP-16/Ara-C intensification
Lasso di tempo: 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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Collaboratori e investigatori
Sponsor
Collaboratori
Investigatori
- Cattedra di studio: Robert J. Wells, MD, Children's Hospital Medical Center, Cincinnati
Studiare le date dei record
Studia le date principali
Inizio studio
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Stima)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Neoplasie per tipo istologico
- Neoplasie
- Malattie del midollo osseo
- Malattie ematologiche
- Sindromi mielodisplastiche
- Leucemia
- Leucemia, mieloide
- Leucemia, mieloide, acuta
- Effetti fisiologici delle droghe
- Meccanismi molecolari dell'azione farmacologica
- Agenti antinfettivi
- Agenti del sistema nervoso periferico
- Agenti antivirali
- Inibitori della sintesi degli acidi nucleici
- Inibitori enzimatici
- Analgesici
- Agenti del sistema sensoriale
- Agenti antinfiammatori
- Agenti antireumatici
- Antimetaboliti, Antineoplastici
- Antimetaboliti
- Agenti antineoplastici
- Agenti immunosoppressivi
- Fattori immunologici
- Agenti antineoplastici, fitogenici
- Inibitori della topoisomerasi II
- Inibitori della topoisomerasi
- Agenti dermatologici
- Oligoelementi
- Micronutrienti
- Agenti di controllo riproduttivo
- Agenti abortivi, non steroidei
- Agenti abortivi
- Antagonisti dell'acido folico
- Etoposide
- Citarabina
- Metotrexato
- Mitoxantrone
- Cladribina
- Idrocortisone
- Idrocortisone 17-butirrato 21-propionato
- Acetato di idrocortisone
- Idrocortisone emisuccinato
- Cobalto
Altri numeri di identificazione dello studio
- 2951
- CCG-2951
- CDR0000064907 (Altro identificatore: Clinical Trials.gov)
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .