Combination Chemotherapy With or Without Monoclonal Antibody Therapy Followed by Stem Cell Transplant in Treating Patients With Acute Myeloid Leukemia - Full Text View

Sponsor:	Eastern Cooperative Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00049517

Purpose

RATIONALE: Giving combination chemotherapy before a stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the transplanted stem cells. When the healthy stem cells are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. If the patient's stem cells are to be transplanted, the patient is also treated with a monoclonal antibody, such as gemtuzumab ozogamicin, to kill any remaining cancer cells or deliver cancer-killing substances to them without harming normal cells. It is not yet known whether combination chemotherapy is more effective with or without gemtuzumab ozogamicin followed by stem cell transplant in treating acute myeloid leukemia.

PURPOSE: This randomized phase III trial is studying combination chemotherapy, gemtuzumab ozogamicin, and stem cell transplant to see how well they work compared to combination chemotherapy and peripheral stem cell transplant alone in treating patients with acute myeloid leukemia.

Condition	Intervention	Phase
Leukemia	Biological: filgrastim Biological: sargramostim Drug: busulfan Drug: cyclophosphamide Drug: cytarabine Drug: daunorubicin hydrochloride Drug: gemtuzumab ozogamicin	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
Official Title:	A Phase III Trial in Adult Acute Myeloid Leukemia: Daunorubicin Dose-Intensification and Gemtuzumab-Ozogamicin Consolidation Therapy Prior to Autologous Stem Cell Transplantation

Resource links provided by NLM:

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood

Drug Information available for: Cyclophosphamide Busulfan Cytarabine hydrochloride Daunorubicin Daunorubicin hydrochloride Filgrastim Sargramostim Gemtuzumab ozogamicin Cytarabine

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Disease-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall survival [ Designated as safety issue: No ]
Complete remission rates [ Designated as safety issue: No ]
Impact of allogeneic stem cell transplantation [ Designated as safety issue: No ]
Effect of gemtuzumab ozogamicin on in vivo purging using pathologic and molecular correlates [ Designated as safety issue: No ]
Safety [ Designated as safety issue: Yes ]

Estimated Enrollment:	830
Study Start Date:	December 2002
Estimated Primary Completion Date:	March 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I (induction therapy): Active Comparator Patients receive standard-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine IV continuously on days 1-7. Patients may receive a second course of induction therapy if complete remission (CR) is not achieved after the first course.	Drug: cytarabine Given as a continuous infusion Drug: daunorubicin hydrochloride Given IV
Arm II (induction therapy): Experimental Patients receive high-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine as in arm I. Patients may receive a second course of induction therapy if CR is not achieved after the first course. The second course is administered as in arm I.	Drug: cytarabine Given as a continuous infusion Drug: daunorubicin hydrochloride Given IV
Arm I (conditioning/transplant): Active Comparator Patients receive conditioning comprising busulfan IV every 6 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2. Patients then undergo autologous peripheral blood stem cell (PBSC) transplantation on day 0. Patients receive sargramostim (GM-CSF) or filgrastim (G-CSF) IV or subcutaneously (SC) beginning on day 0 and continuing until blood counts recover.	Biological: filgrastim Given IV or as an injection Biological: sargramostim Given IV or as an injection Drug: busulfan Given IV Drug: cyclophosphamide Given IV
Arm II (conditioning/transplant): Experimental Patients receive gemtuzumab ozogamicin IV over 2 hours on day 1 and GM-CSF SC or IV beginning on day 10 and continuing until blood counts recover. Within 2-3 weeks after blood count recovery, patients receive conditioning and undergo autologous PBSC transplantation as in arm I.	Biological: filgrastim Given IV or as an injection Biological: sargramostim Given IV or as an injection Drug: busulfan Given IV Drug: cyclophosphamide Given IV Drug: gemtuzumab ozogamicin Given IV

Show Detailed Description

Eligibility

Ages Eligible for Study:	16 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Morphologically confirmed acute myeloid leukemia (AML) (greater than 20% blasts in the peripheral blood or marrow) meeting any of the following criteria:
- Recurrent cytogenetic translocations
  - t(8;21)(q22;q22)
  - Bone marrow eosinophil abnormalities
    - inv(16)(p13;q22)
    - t(16;16)(p13;q22)
  - 11q23 abnormalities
- Multilineage dysplasia without presence of myelodysplastic syndromes (MDS)
- Minimally differentiated AML
- AML without maturation
- AML with maturation
- AML not otherwise categorized
- Acute myelomonocytic leukemia
- Acute monocytic leukemia
- Acute erythroid leukemia
- Acute megakaryocytic leukemia
- Acute basophilic leukemia
The following types of AML are excluded:
- Recurrent cytogenetic translocations
  - Acute promyelocytic leukemia (PML) with t(15;17)(q22;q21)
  - Variant acute PML with t(v;17)
- Multilineage dysplasia with prior MDS
- Acute panmyelosis with myelofibrosis
No blastic transformation of chronic myelogenous leukemia
No secondary AML (chemotherapy-induced or evolved from MDS)
CNS disease allowed
Patients undergoing allogeneic transplantation must have a sibling donor match defined as HLA match or haplotype match with one locus mismatch on other haplotype

PATIENT CHARACTERISTICS:

Age

16 to 60

Performance status

ECOG 0-4

Life expectancy

Not specified

Hematopoietic

See Disease Characteristics

Hepatic

Bilirubin no greater than 2.0 mg/dL (unless related to Gilbert's syndrome or hemolysis)
AST less than 4 times upper limit of normal (ULN)
Alkaline phosphatase less than 4 times ULN

Renal

Creatinine no greater than 2.0 mg/dL
Creatinine clearance at least 50 mL/min

Cardiovascular

LVEF at least 45% by post-induction MUGA
No significant cardiac disease requiring active therapy (e.g., digoxin, diuretics, antiarrhythmics, or antianginal medications)

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

No prior biologic therapy

Chemotherapy

No prior cytotoxic chemotherapy for any malignancy
Prior hydroxyurea allowed

Endocrine therapy

Prior corticosteroids allowed

Radiotherapy

No prior radiotherapy for any malignancy

Surgery

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00049517

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Locations

United States, Alabama
Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
Birmingham, Alabama, United States, 35294
United States, Arizona
Mayo Clinic Scottsdale
Scottsdale, Arizona, United States, 85259-5499
United States, Colorado
Aurora Presbyterian Hospital
Aurora, Colorado, United States, 80012
CCOP - Colorado Cancer Research Program
Denver, Colorado, United States, 80224-2522
Exempla Lutheran Medical Center
Wheat Ridge, Colorado, United States, 80033
Hope Cancer Care Center at Longmont United Hospital
Longmont, Colorado, United States, 80502
Presbyterian - St. Luke's Medical Center
Denver, Colorado, United States, 80218
North Colorado Medical Center
Greeley, Colorado, United States, 80631
North Suburban Medical Center
Thornton, Colorado, United States, 80229
Penrose Cancer Center at Penrose Hospital
Colorado Springs, Colorado, United States, 80933
Porter Adventist Hospital
Denver, Colorado, United States, 80210
McKee Medical Center
Loveland, Colorado, United States, 80539
Rose Medical Center
Denver, Colorado, United States, 80220
Sky Ridge Medical Center
Lone Tree, Colorado, United States, 80124
St. Anthony Central Hospital
Denver, Colorado, United States, 80204
St. Joseph Hospital
Denver, Colorado, United States, 80218
St. Mary - Corwin Regional Medical Center
Pueblo, Colorado, United States, 81004
St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center
Grand Junction, Colorado, United States, 81502
Swedish Medical Center
Englewood, Colorado, United States, 80110
United States, Florida
Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - West
Boca Raton, Florida, United States, 33428
Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - Main Campus
Boca Raton, Florida, United States, 33486
University of Florida Shands Cancer Center
Gainesville, Florida, United States, 32610-0232
University of Miami Sylvester Comprehensive Cancer Center - Miami
Miami, Florida, United States, 33136
United States, Georgia
Winship Cancer Institute of Emory University
Altanta, Georgia, United States, 30322
United States, Illinois
Advocate Lutheran General Cancer Care Center
Park Ridge, Illinois, United States, 60068-1174
Cancer Care and Hematology Specialists of Chicagoland - Niles
Niles, Illinois, United States, 60714
Carle Cancer Center at Carle Foundation Hospital
Urbana, Illinois, United States, 61801
CCOP - Carle Cancer Center
Urbana, Illinois, United States, 61801
Hematology Oncology Associates - Skokie
Skokie, Illinois, United States, 60076
Hematology and Oncology Associates
Chicago, Illinois, United States, 60611
Evanston Northwestern Healthcare - Evanston Hospital
Evanston, Illinois, United States, 60201-1781
Joliet Oncology-Hematology Associates, Limited - West
Joliet, Illinois, United States, 60435
La Grange Oncology Associates - Geneva
Naperville, Illinois, United States, 60563
Midwest Center for Hematology/Oncology
Joliet, Illinois, United States, 60432
North Shore Oncology and Hematology Associates, Limited - Libertyville
Libertyville, Illinois, United States, 60048
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611-3013
United States, Indiana
Fort Wayne Medical Oncology and Hematology
Fort Wayne, Indiana, United States, 46815
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202-5289
United States, Massachusetts
Tufts-NEMC Cancer Center
Boston, Massachusetts, United States, 02111
United States, Michigan
Borgess Medical Center
Kalamazoo, Michigan, United States, 49001
Bronson Methodist Hospital
Kalamazoo, Michigan, United States, 49007
West Michigan Cancer Center
Kalamazoo, Michigan, United States, 49007-3731
United States, Minnesota
CCOP - Metro-Minnesota
Saint Louis Park, Minnesota, United States, 55416
Mercy and Unity Cancer Center at Unity Hospital
Fridley, Minnesota, United States, 55432
Fairview Southdale Hospital
Edina, Minnesota, United States, 55435
Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
Robbinsdale, Minnesota, United States, 55422-2900
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
Mercy and Unity Cancer Center at Mercy Hospital
Coon Rapids, Minnesota, United States, 55433
Fairview Ridges Hospital
Burnsville, Minnesota, United States, 55337
MeritCare Bemidji
Bemidji, Minnesota, United States, 56601
Minnesota Oncology Hematology, PA - Maplewood
Maplewood, Minnesota, United States, 55109
Minnesota Oncology Hematology, PA - Woodbury
Woodbury, Minnesota, United States, 55125
Park Nicollet Cancer Center
Saint Louis Park, Minnesota, United States, 55416
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
Minneapolis, Minnesota, United States, 55407
United Hospital
Saint Paul, Minnesota, United States, 55102
Ridgeview Medical Center
Waconia, Minnesota, United States, 55387
United States, Montana
Great Falls Clinic - Main Facility
Great Falls, Montana, United States, 59405
Bozeman Deaconess Cancer Center
Bozeman, Montana, United States, 59715
CCOP - Montana Cancer Consortium
Billings, Montana, United States, 59101
Community Medical Center
Missoula, Montana, United States, 59801
Glacier Oncology, PLLC
Kalispell, Montana, United States, 59901
Billings Clinic - Downtown
Billings, Montana, United States, 59107-7000
Guardian Oncology and Center for Wellness
Missoula, Montana, United States, 59804
Hematology-Oncology Centers of the Northern Rockies - Billings
Billings, Montana, United States, 59101
Kalispell Medical Oncology at KRMC
Kalispell, Montana, United States, 59901
Kalispell Regional Medical Center
Kalispell, Montana, United States, 59901

Great Falls, Montana, United States, 59405
Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
Missoula, Montana, United States, 59807
Montana Cancer Specialists at Montana Cancer Center
Missoula, Montana, United States, 59807-7877
Northern Rockies Radiation Oncology Center
Billings, Montana, United States, 59101
St. James Healthcare Cancer Care
Butte, Montana, United States, 59701
St. Peter's Hospital
Helena, Montana, United States, 59601
St. Vincent Healthcare Cancer Care Services
Billings, Montana, United States, 59101
United States, New York
Albert Einstein Cancer Center at Albert Einstein College of Medicine
Bronx, New York, United States, 10461
NYU Cancer Institute at New York University Medical Center
New York, New York, United States, 10016
United States, North Dakota
CCOP - MeritCare Hospital
Fargo, North Dakota, United States, 58122
MeritCare Broadway
Fargo, North Dakota, United States, 58122
United States, Ohio
Aultman Cancer Center at Aultman Hospital
Canton, Ohio, United States, 44710-1799
St. Rita's Medical Center
Lima, Ohio, United States, 45801
Mercy Cancer Center at Mercy Medical Center
Canton, Ohio, United States, 44708
Jewish Hospital Cancer Center
Cincinnati, Ohio, United States, 45236
United States, Pennsylvania
Penn State Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
Fox Chase Cancer Center - Philadelphia
Philadelphia, Pennsylvania, United States, 19111-2497
Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
Wilkes-Barre, Pennsylvania, United States, 18711
Geisinger Cancer Institute at Geisinger Health
Danville, Pennsylvania, United States, 17822-0001
Geisinger Medical Group - Scenery Park
State College, Pennsylvania, United States, 16801
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104-4283
UPMC Cancer Centers
Pittsburgh, Pennsylvania, United States, 15232
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-6838
United States, Virginia
Virginia Commonwealth University Massey Cancer Center
Richmond, Virginia, United States, 23298-0037
United States, Wisconsin
Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center
La Crosse, Wisconsin, United States, 54601
Marshfield Clinic - Marshfield Center
Marshfield, Wisconsin, United States, 54449
Marshfield Clinic - Weston Center
Weston, Wisconsin, United States, 54476
Marshfield Clinic Cancer Care at Regional Cancer Center
Eau Claire, Wisconsin, United States, 54701
Ministry Medical Group at Saint Mary's Hospital
Rhinelander, Wisconsin, United States, 54501
Saint Joseph's Hospital
Marshfield, Wisconsin, United States, 54449
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792-6164
United States, Wyoming
Welch Cancer Center at Sheridan Memorial Hospital
Sheridan, Wyoming, United States, 82801
Israel
Rambam Medical Center
Haifa, Israel, 31096

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Hugo E. Fernandez, MD

H. Lee Moffitt Cancer Center and Research Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Fernandez HF, Sun Z, Yao X, Litzow MR, Luger SM, Paietta EM, Racevskis J, Dewald GW, Ketterling RP, Bennett JM, Rowe JM, Lazarus HM, Tallman MS. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med. 2009 Sep 24;361(13):1249-59.

Fernandez HF, Sun Z, Bennett JM, et al.: A single dose of gemtuzumab-ozogamicin (GO) in consolidation prior to autologous transplant for younger patients with newly diagnosed acute myeloid (AML) is safe but has no effect on disease free survival: interim results of Eastern Cooperative Oncology Group study (E1900). [Abstract] Biol Blood Marrow Transplant 14 (2): A-52, 21-2, 2008.

Vance GH, Kim H, Hicks GA, Cherry AM, Higgins R, Hulshizer RL, Tallman MS, Fernandez HF, Dewald GW. Utility of interphase FISH to stratify patients into cytogenetic risk categories at diagnosis of AML in an Eastern Cooperative Oncology Group (ECOG) clinical trial (E1900). Leuk Res. 2006 Sep 20; [Epub ahead of print]

Fernandez HF, Kim HT, Bennett JM, et al.: Gemtuzumab-ozogamicin (GO; mylotarg®) as part of consolidation therapy for AML before autograft: low incidence of hepatic veno-occlusive disease. [Abstract] Biol Blood Marrow Transplant 11 (2 Suppl 1): A-187, 2005.

Responsible Party:	ECOG Group Chair's Office ( Robert L. Comis )
Study ID Numbers:	CDR0000258113, ECOG-1900
Study First Received:	November 12, 2002
Last Updated:	October 1, 2009
ClinicalTrials.gov Identifier:	NCT00049517 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

adult acute basophilic leukemia
adult acute monocytic leukemia (M5b)
adult acute eosinophilic leukemia
adult acute erythroid leukemia (M6)
adult erythroleukemia (M6a)
adult pure erythroid leukemia (M6b)
adult acute megakaryoblastic leukemia (M7)
adult acute minimally differentiated myeloid leukemia (M0)
adult acute myeloblastic leukemia with maturation (M2)

adult acute myeloblastic leukemia without maturation (M1)
adult acute myelomonocytic leukemia (M4)
adult acute monoblastic leukemia (M5a)
untreated adult acute myeloid leukemia
adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with 11q23 (MLL) abnormalities

Additional relevant MeSH terms:

Antimetabolites
Daunorubicin
Anti-Infective Agents
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Cyclophosphamide
Antibiotics, Antineoplastic
Leukemia, Myeloid, Acute
Antibodies, Monoclonal
Leukemia

Therapeutic Uses
Alkylating Agents
Cytarabine
Neoplasms by Histologic Type
Leukemia, Myeloid
Gemtuzumab
Immunosuppressive Agents
Antiviral Agents
Pharmacologic Actions
Neoplasms
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents

ClinicalTrials.gov processed this record on November 25, 2009