S9920 Busulfan Compared With Cyclophosphamide in Patients Undergoing Total-Body Irradiation Plus Peripheral Stem Cell Transplantation for Advanced Myelodysplastic Syndrome or Related Acute Myeloid Leukemia
A Phase III Randomized Study Comparing Busulfan-Total Body Irradiation Versus Cyclophosphamide-Total Body Irradiation Preparative Regimen in Patients With Advanced Myelodysplastic Syndrome (MDS) or MDS-Related Acute Myeloid Leukemia (AML) Undergoing HLA-Identical Sibling Peripheral Blood Stem Cell Transplantation, (A BMT Study)
RATIONALE: Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill tumor cells. It is not yet known if total-body irradiation plus peripheral stem cell transplantation is more effective with busulfan or with cyclophosphamide for myelodysplastic syndrome or acute myeloid leukemia.
PURPOSE: Randomized phase III trial to compare the effectiveness of busulfan with that of cyclophosphamide in patients undergoing total-body irradiation plus peripheral stem cell transplantation for advanced myelodysplastic syndrome or related acute myeloid leukemia.
Aperçu de l'étude
Statut
Les conditions
Description détaillée
OBJECTIVES: I. Compare event free survival after total body irradiation (TBI) plus busulfan versus TBI plus cyclophosphamide followed by allogeneic peripheral blood stem cell transplantation in patients with advanced myelodysplastic syndrome (MDS) or MDS related acute myeloid leukemia. II. Determine the distribution of pharmacokinetic parameters for busulfan in those patients randomized to the busulfan treatment arm. III. Investigate the prognostic significance for event free survival of prior history of red cell transfusions, cytogenetic pattern, and of functional drug resistance at diagnosis in these patients. IV. Estimate the frequencies of cytogenetic and genetic changes during disease progression in these patients.
OUTLINE: This a randomized, multicenter study. Patients are stratified according to age (40 and under vs 41-55) and diagnosis and International Prognostic Scoring System (IPSS) risk group (myelodysplastic syndrome (MDS)/IPSS - intermediate 1 vs MDS/IPSS - intermediate 2 vs MDS/IPSS high risk vs MDS related acute myeloid leukemia). Patients are randomized to one of two treatment arms. Arm I: Patients receive busulfan IV over 2 hours every 6 hours on days -7 to -4 for a total of 16 doses. Arm II: Patients receive cyclophosphamide IV over 2 hours on days -5 and -4. Patients receive total body irradiation (TBI) twice a day on days -3 to -1; peripheral blood stem cell transplantation from genotypically HLA identical sibling on day 0; cyclosporine IV every 12 hours on days -1 to 60, and then tapering in the absence of graft versus host disease; and methotrexate IV on days 1, 3, 6, and 11. Patients are followed every 6 months for 5 years.
PROJECTED ACCRUAL: A total of 240 patients (120 per treatment arm) will be accrued for this study over 5 years.
Type d'étude
Inscription (Anticipé)
Phase
- Phase 3
Contacts et emplacements
Lieux d'étude
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Ontario
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Toronto, Ontario, Canada, M5G 2M9
- Princess Margaret Hospital
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Arizona
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Phoenix, Arizona, États-Unis, 85062-2989
- Good Samaritan Medical Center
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Tucson, Arizona, États-Unis, 85724
- Arizona Cancer Center
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Arkansas
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Little Rock, Arkansas, États-Unis, 72205
- University of Arkansas for Medical Sciences
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California
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Berkeley, California, États-Unis, 94704
- Alta Bates Comprehensive Cancer Center
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Duarte, California, États-Unis, 91010-3000
- Cancer Center and Beckman Research Institute, City of Hope
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La Jolla, California, États-Unis, 92037
- Scripps Clinic
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Los Angeles, California, États-Unis, 90095-1781
- Jonsson Comprehensive Cancer Center, UCLA
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Los Angeles, California, États-Unis, 90033-0804
- USC/Norris Comprehensive Cancer Center and Hospital
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Orange, California, États-Unis, 92868
- Chao Family Comprehensive Cancer Center
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Orange, California, États-Unis, 92613-5600
- St. Joseph Hospital - Orange
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Sacramento, California, États-Unis, 95816
- Sutter Cancer center
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Sacramento, California, États-Unis, 95817
- University of California Davis Cancer Center
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Stanford, California, États-Unis, 94305-5408
- Stanford University Medical Center
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Walnut Creek, California, États-Unis, 94598
- Northern California Cancer Specialists Medical Clinic
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Colorado
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Denver, Colorado, États-Unis, 80010
- University Of Colorado Cancer Center
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Hawaii
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Honolulu, Hawaii, États-Unis, 96813
- Queen's Medical Center
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Honolulu, Hawaii, États-Unis, 96813
- Cancer Research Center of Hawaii
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Honolulu, Hawaii, États-Unis, 96817
- St. Francis Medical Center
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Idaho
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Boise, Idaho, États-Unis, 83712
- Mountain States Tumor Institute
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Illinois
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Maywood, Illinois, États-Unis, 60153
- Loyola University Medical Center
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Kansas
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Kansas City, Kansas, États-Unis, 66160-7357
- University of Kansas Medical Center
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Wichita, Kansas, États-Unis, 67214
- Cancer Center of Kansas - Wichita
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Wichita, Kansas, États-Unis, 67214-3882
- CCOP - Wichita
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Kentucky
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Lexington, Kentucky, États-Unis, 40536-0084
- Albert B. Chandler Medical Center, University of Kentucky
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Lexington, Kentucky, États-Unis, 40536-0093
- Lucille Parker Markey Cancer Center, University of Kentucky
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Louisiana
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New Orleans, Louisiana, États-Unis, 70112
- Tulane University School of Medicine
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New Orleans, Louisiana, États-Unis, 70112
- MBCCOP - LSU Health Sciences Center
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New Orleans, Louisiana, États-Unis, 70112-2822
- Louisiana State University School of Medicine
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New Orleans, Louisiana, États-Unis, 70115
- Memorial Medical Center
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Shreveport, Louisiana, États-Unis, 71130-3932
- Louisiana State University Health Sciences Center - Shreveport
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Massachusetts
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Boston, Massachusetts, États-Unis, 02118
- Boston Medical Center
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Boston, Massachusetts, États-Unis, 02118
- Cancer Research Center
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Michigan
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Ann Arbor, Michigan, États-Unis, 48109-0752
- University of Michigan Comprehensive Cancer Center
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Detroit, Michigan, États-Unis, 48202
- Henry Ford Hospital
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Detroit, Michigan, États-Unis, 48201-1379
- Barbara Ann Karmanos Cancer Institute
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Mississippi
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Jackson, Mississippi, États-Unis, 39216-4505
- University of Mississippi Medical Center
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Missouri
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Saint Louis, Missouri, États-Unis, 63110-0250
- St. Louis University Health Sciences Center
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Springfield, Missouri, États-Unis, 65807
- CCOP - Cancer Research for the Ozarks
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Springfield, Missouri, États-Unis, 65804
- St. John's Health System
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New York
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New York, New York, États-Unis, 10032
- Herbert Irving Comprehensive Cancer Center
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Ohio
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Cincinnati, Ohio, États-Unis, 45236
- Jewish Hospital of Cincinnati, Inc.
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Cleveland, Ohio, États-Unis, 44195
- Cleveland Clinic Taussig Cancer Center
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Dayton, Ohio, États-Unis, 45409
- Miami Valley Hospital
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Kettering, Ohio, États-Unis, 45429
- CCOP - Dayton
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Oklahoma
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Oklahoma City, Oklahoma, États-Unis, 73190
- University of Oklahoma Health Sciences Center
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Oregon
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Portland, Oregon, États-Unis, 97213
- CCOP - Columbia River Program
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Portland, Oregon, États-Unis, 97201-3098
- Oregon Cancer Center
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Portland, Oregon, États-Unis, 97225
- Providence St. Vincent Medical Center
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Portland, Oregon, États-Unis, 97210
- Legacy Cancer Services
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Texas
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Fort Sam Houston, Texas, États-Unis, 78234
- Brooke Army Medical Center
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Lackland Air Force Base, Texas, États-Unis, 78236-5300
- Wilford Hall - 59th Medical Wing
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Lubbock, Texas, États-Unis, 79423
- Texas Tech University Health Science Center
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Lubbock, Texas, États-Unis, 79430
- Health Science Center
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San Antonio, Texas, États-Unis, 78284-7811
- University of Texas Health Science Center at San Antonio
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San Antonio, Texas, États-Unis, 78229
- Methodist Health Care System
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Temple, Texas, États-Unis, 76508
- Scott and White Clinic
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Temple, Texas, États-Unis, 76508
- CCOP - Scott and White Hospital
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Utah
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Salt Lake City, Utah, États-Unis, 84112
- Huntsman Cancer Institute
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Salt Lake City, Utah, États-Unis, 84143
- LDS Hospital
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Washington
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Seattle, Washington, États-Unis, 98101
- CCOP - Virginia Mason Research Center
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Seattle, Washington, États-Unis, 98104
- Swedish Cancer Institute
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Seattle, Washington, États-Unis, 98109-1024
- Fred Hutchinson Cancer Research Center
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Seattle, Washington, États-Unis, 98195-6043
- University of Washington Medical Center
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Tacoma, Washington, États-Unis, 98405-0986
- CCOP - Northwest
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Tacoma, Washington, États-Unis, 98401-2197
- Franciscan Health System
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
DISEASE CHARACTERISTICS: Cytologically confirmed myelodysplastic syndrome (MDS) Increased blasts (i.e., greater than 1 to 30% peripheral blood blasts and/or 5 to 30% bone marrow blasts) AND International Prognostic Score intermediate 1, intermediate 2, or high risk Refractory anemia with excess blasts OR Refractory anemia with excess blasts in transformation (no presence of auer rods as sole criteria) OR Chronic myelomonocytic leukemia Greater than 1% blasts in the peripheral blood and/or at least 5% blasts in the bone marrow OR MDS related acute myeloid leukemia Arising after documented MDS of at least 60 days Absolute peripheral blast count no greater than 5,000/mm3 Must have genotypically HLA identical sibling donor Must also be enrolled on SWOG-S9910 and SWOG-9007
PATIENT CHARACTERISTICS: Age: 16 to 55 Performance status: Zubrod 0-2 Life expectancy: Not specified Hematopoietic: See Disease Characteristics Hepatic: Not specified Renal: Not specified Other: No prior malignancy within past 5 years except: Adequately treated basal cell or squamous cell skin cancer Carcinoma in situ of the cervix Adequately treated stage I or II cancer in complete remission HIV negative Not pregnant or nursing Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY: Biologic therapy: No autologous peripheral stem cell transplantation prior to diagnosis of myelodysplastic syndrome (MDS) or MDS related acute myeloid leukemia Chemotherapy: No prior chemotherapy for MDS or MDS related acute myeloid leukemia except oral chemotherapy to control leukocytosis or thrombocytosis (e.g., hydroxyurea or etoposide) Endocrine therapy: Not specified Radiotherapy: No radiotherapy prior to diagnosis of MDS or MDS related acute myeloid leukemia Surgery: Not specified
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Expérimental: traitement
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jour 0
arm 1: 0.44 mg/kg every 6 hours, IV over 2 hours, day -7 to -4
arm 2: 60 mg/kg every 24 hrs for 2 doses, IV over 2 hrs, days -5 and -4
both arms per published schedule
GVHD: 15 mg/m2 day 1, 10 mg/m2 day 3, 6 and 11 by IV
both arms: 1200 cGy total dose (6 x 200 fractions)
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Délai |
|---|---|
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Event-free survival
Délai: every 6 months after stem cell infusion until death or 5 years
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every 6 months after stem cell infusion until death or 5 years
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Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Les enquêteurs
- Chaise d'étude: Jeanne E. Anderson, MD, Katmai Oncology Group
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
- anémie réfractaire avec excès de blastes
- anémie réfractaire avec excès de blastes en transformation
- leucémie myélomonocytaire chronique
- syndromes myélodysplasiques de novo
- syndromes myélodysplasiques secondaires
- leucémie myéloïde aiguë secondaire
- syndromes myélodysplasiques de l'enfant
- leucémie myéloïde aiguë de l'adulte non traitée
Termes MeSH pertinents supplémentaires
- Processus pathologiques
- Tumeurs par type histologique
- Tumeurs
- Maladie
- Maladies de la moelle osseuse
- Maladies hématologiques
- Conditions précancéreuses
- Syndrome
- Syndromes myélodysplasiques
- Leucémie
- Leucémie myéloïde
- Leucémie, myéloïde, aiguë
- Préleucémie
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Agents anti-infectieux
- Inhibiteurs de la synthèse des acides nucléiques
- Inhibiteurs d'enzymes
- Agents antirhumatismaux
- Antimétabolites, Antinéoplasique
- Antimétabolites
- Agents antinéoplasiques
- Agents immunosuppresseurs
- Facteurs immunologiques
- Agents antinéoplasiques, alkylants
- Agents d'alkylation
- Agonistes myéloablatifs
- Agents dermatologiques
- Agents antifongiques
- Agents de contrôle de la reproduction
- Agents abortifs, non stéroïdiens
- Agents abortifs
- Antagonistes de l'acide folique
- Inhibiteurs de la calcineurine
- Cyclophosphamide
- Méthotrexate
- Busulfan
- Ciclosporine
- Cyclosporines
Autres numéros d'identification d'étude
- S9920 (Autre identifiant: SWOG)
- U10CA032102 (Subvention/contrat des NIH des États-Unis)
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