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Combination Chemotherapy With or Without Monoclonal Antibody Therapy in Treating Patients With AML Leukemia

Information source: Eastern Cooperative Oncology Group
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Leukemia

Intervention: sargramostim (Biological); busulfan (Drug); cyclophosphamide (Drug); cytarabine (Drug); gemtuzumab ozogamicin (GO) (Drug); Daunorubicin (Drug); Autologous HCT (Procedure); Allogeneic HCT (Procedure)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: Eastern Cooperative Oncology Group

Official(s) and/or principal investigator(s):
Hugo F. Fernandez, MD, Study Chair, Affiliation: H. Lee Moffitt Cancer Center and Research Institute

Summary

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.

Clinical Details

Official title: A Phase III Trial in Adult Acute Myeloid Leukemia: Daunorubicin Dose-Intensification Prior to Risk-Allocated Autologous Stem Cell Transplantation

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Overall Survival (Induction Phase)

Disease-free Survival (Consolidation Phase)

Secondary outcome: Overall Survival (Consolidation Phase)

Detailed description: OBJECTIVES:

- To compare the overall survival (OS) between two induction regimens (standard versus

dose intense daunorubicin and cytarabine) in patients with de novo AML.

- To compare disease-free survival (DFS) between two consolidation regimens.

- To compare overall survival between two consolidation regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to induction therapy (standard-dose daunorubicin vs high-dose daunorubicin).

- Induction therapy: Patients are randomized to 1 of 2 induction arms.

- Standard: Patients receive standard-dose daunorubicin IV over 10-15 minutes on

days 1-3 and cytarabine IV continuously on days 1-7.

- High dose: Patients receive high-dose daunorubicin IV over 10-15 minutes on days

1-3 and cytarabine as in arm I. Patients in both arms may receive a second course of induction therapy if complete remission (CR) is not achieved after the first course. The second course is administered as in arm I to all patients. Patients who don't achieve CR after 2 courses of induction therapy are removed from study. Patients who achieve CR after induction therapy proceed to post-remission therapy with EITHER allogeneic transplantation only (on or off study) OR consolidation therapy and autologous transplantation (on study), according to risk status and donor status. Patients who are considered at intermediate or high risk for relapse (unfavorable cytogenetics/high WBC) and have a suitable related donor undergo an allogeneic transplantation. Patients with intermediate-risk cytogenetics, WBC no greater than 100,000/mm^3, and appropriate donors have the option of undergoing allogeneic transplantation.

- Allogeneic transplantation: Within 1-3 months after recovery from induction therapy,

patients receive busulfan IV every 6 hours on days - 7 to -4 and cyclophosphamide IV

over 4 hours on days - 3 and -2. Allogeneic bone marrow or peripheral blood stem cells

(PBSCs) are infused on day 0. Patients receive graft-vs-host disease (GVHD) prophylaxis

comprising cyclosporine IV over 1-4 hours beginning on day - 1 and then orally (when

tolerated) twice daily until day 180. Alternatively, patients may receive tacrolimus IV

over 24 hours beginning on day - 1 and then orally twice daily until day 180. Patients

also receive methotrexate IV on days 1, 3, 6, and 11. Patients who do not meet the criteria for allogeneic transplantation (i. e., are favorable risk or do not have a matching related donor) or who opt not to undergo allogeneic transplantation proceed to consolidation therapy followed by randomization to 1 of 2 autologous transplantation arms.

- Consolidation therapy: Beginning 2-8 weeks after recovery from induction therapy,

patients receive high-dose cytarabine IV over 3 hours every 12 hours on days 1, 3, and 5. A second course is administered 3 weeks after blood recovery. Patients receive filgrastim (G-CSF) subcutaneously (SC) daily for 4 days and then autologous PBSCs are harvested by leukapheresis.

- Autologous stem cell transplantation: Patients are randomized to 1 of 2 autologous

transplantation arms.

- Arm I: Within 1 month after PBSC collection, 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 PBSC transplantation

on day 0. Patients receive sargramostim (GM-CSF) or G-CSF IV or SC beginning on day 0 and continuing until blood counts recover.

- Arm II (closed to accrual as of 10/4/2007): Within 2-4 weeks after PBSC

collection, 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. Patients are followed monthly for 1 year, every 2 months for 1 year, and then every 3 months for up to 7 years. ACTUAL ACCRUAL: A total of 657 patients were accrued for this study.

Eligibility

Minimum age: 16 Years. Maximum age: 60 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- 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

- Patients undergoing allogeneic transplantation must have a sibling donor match

defined as human leukocyte antigen (HLA) match or haplotype match with one locus mismatch on other haplotype

- Age 16 to 60

- Eastern Cooperative Oncology Group (ECOG) performance status 0-4

- Aspartate aminotransferase (AST) less than 4 times upper limit of normal (ULN)

- Alkaline phosphatase less than 4 times ULN

- Creatinine no greater than 2. 0 mg/dL

- Creatinine clearance at least 50 mL/min

- Left ventricular ejection fraction (LVEF) at least 45% by post-induction multigated

acquisition (MUGA) scan

- Negative pregnancy test

- Fertile patients must use effective contraception

- HIV negative

- Prior hydroxyurea allowed

- Prior corticosteroids allowed

Exclusion Criteria:

- 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

- Blastic transformation of chronic myelogenous leukemia

- Secondary AML (chemotherapy-induced or evolved from MDS)

- Pregnant or nursing

- Bilirubin greater than 2. 0 mg/dL (unless related to Gilbert's syndrome or

hemolysis)

- Significant cardiac disease requiring active therapy (e. g., digoxin, diuretics,

antiarrhythmics, or antianginal medications)

- Prior biologic therapy

- Prior cytotoxic chemotherapy for any malignancy

- Prior radiotherapy for any malignancy

Locations and Contacts

Rambam Medical Center, Haifa 31096, Israel

Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham, Birmingham, Alabama 35294, United States

Mayo Clinic Scottsdale, Scottsdale, Arizona 85259-5499, United States

Aurora Presbyterian Hospital, Aurora, Colorado 80012, United States

Penrose Cancer Center at Penrose Hospital, Colorado Springs, Colorado 80933, United States

CCOP - Colorado Cancer Research Program, Denver, Colorado 80224-2522, United States

Porter Adventist Hospital, Denver, Colorado 80210, United States

Presbyterian - St. Luke's Medical Center, Denver, Colorado 80218, United States

Rose Medical Center, Denver, Colorado 80220, United States

St. Anthony Central Hospital, Denver, Colorado 80204, United States

St. Joseph Hospital, Denver, Colorado 80218, United States

Swedish Medical Center, Englewood, Colorado 80110, United States

St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center, Grand Junction, Colorado 81502, United States

North Colorado Medical Center, Greeley, Colorado 80631, United States

Sky Ridge Medical Center, Lone Tree, Colorado 80124, United States

Hope Cancer Care Center at Longmont United Hospital, Longmont, Colorado 80502, United States

McKee Medical Center, Loveland, Colorado 80539, United States

St. Mary - Corwin Regional Medical Center, Pueblo, Colorado 81004, United States

North Suburban Medical Center, Thornton, Colorado 80229, United States

Exempla Lutheran Medical Center, Wheat Ridge, Colorado 80033, United States

Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - Main Campus, Boca Raton, Florida 33486, United States

Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - West, Boca Raton, Florida 33428, United States

University of Florida Shands Cancer Center, Gainesville, Florida 32610-0232, United States

University of Miami Sylvester Comprehensive Cancer Center - Miami, Miami, Florida 33136, United States

Winship Cancer Institute of Emory University, Altanta, Georgia 30322, United States

Hematology and Oncology Associates, Chicago, Illinois 60611, United States

Robert H. Lurie Comprehensive Cancer Center at Northwestern University, Chicago, Illinois 60611-3013, United States

Evanston Northwestern Healthcare - Evanston Hospital, Evanston, Illinois 60201-1781, United States

Joliet Oncology-Hematology Associates, Limited - West, Joliet, Illinois 60435, United States

Midwest Center for Hematology/Oncology, Joliet, Illinois 60432, United States

North Shore Oncology and Hematology Associates, Limited - Libertyville, Libertyville, Illinois 60048, United States

La Grange Oncology Associates - Geneva, Naperville, Illinois 60563, United States

Cancer Care and Hematology Specialists of Chicagoland - Niles, Niles, Illinois 60714, United States

Advocate Lutheran General Cancer Care Center, Park Ridge, Illinois 60068-1174, United States

Hematology Oncology Associates - Skokie, Skokie, Illinois 60076, United States

Carle Cancer Center at Carle Foundation Hospital, Urbana, Illinois 61801, United States

CCOP - Carle Cancer Center, Urbana, Illinois 61801, United States

Fort Wayne Medical Oncology and Hematology, Fort Wayne, Indiana 46815, United States

Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana 46202-5289, United States

Tufts-NEMC Cancer Center, Boston, Massachusetts 02111, United States

Borgess Medical Center, Kalamazoo, Michigan 49001, United States

Bronson Methodist Hospital, Kalamazoo, Michigan 49007, United States

West Michigan Cancer Center, Kalamazoo, Michigan 49007-3731, United States

MeritCare Bemidji, Bemidji, Minnesota 56601, United States

Fairview Ridges Hospital, Burnsville, Minnesota 55337, United States

Mercy and Unity Cancer Center at Mercy Hospital, Coon Rapids, Minnesota 55433, United States

Fairview Southdale Hospital, Edina, Minnesota 55435, United States

Mercy and Unity Cancer Center at Unity Hospital, Fridley, Minnesota 55432, United States

Minnesota Oncology Hematology, PA - Maplewood, Maplewood, Minnesota 55109, United States

Virginia Piper Cancer Institute at Abbott - Northwestern Hospital, Minneapolis, Minnesota 55407, United States

Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center, Robbinsdale, Minnesota 55422-2900, United States

Mayo Clinic Cancer Center, Rochester, Minnesota 55905, United States

CCOP - Metro-Minnesota, Saint Louis Park, Minnesota 55416, United States

Park Nicollet Cancer Center, Saint Louis Park, Minnesota 55416, United States

United Hospital, Saint Paul, Minnesota 55102, United States

Ridgeview Medical Center, Waconia, Minnesota 55387, United States

Minnesota Oncology Hematology, PA - Woodbury, Woodbury, Minnesota 55125, United States

Billings Clinic - Downtown, Billings, Montana 59107-7000, United States

CCOP - Montana Cancer Consortium, Billings, Montana 59101, United States

Hematology-Oncology Centers of the Northern Rockies - Billings, Billings, Montana 59101, United States

Northern Rockies Radiation Oncology Center, Billings, Montana 59101, United States

St. Vincent Healthcare Cancer Care Services, Billings, Montana 59101, United States

Bozeman Deaconess Cancer Center, Bozeman, Montana 59715, United States

St. James Healthcare Cancer Care, Butte, Montana 59701, United States

Great Falls Clinic, Great Falls, Montana 59405, United States

Great Falls Clinic - Main Facility, Great Falls, Montana 59405, United States

St. Peter's Hospital, Helena, Montana 59601, United States

Glacier Oncology, PLLC, Kalispell, Montana 59901, United States

Kalispell Medical Oncology at KRMC, Kalispell, Montana 59901, United States

Kalispell Regional Medical Center, Kalispell, Montana 59901, United States

Community Medical Center, Missoula, Montana 59801, United States

Guardian Oncology and Center for Wellness, Missoula, Montana 59804, United States

Montana Cancer Center at St. Patrick Hospital and Health Sciences Center, Missoula, Montana 59807, United States

Montana Cancer Specialists at Montana Cancer Center, Missoula, Montana 59807-7877, United States

Albert Einstein Cancer Center at Albert Einstein College of Medicine, Bronx, New York 10461, United States

NYU Cancer Institute at New York University Medical Center, New York, New York 10016, United States

CCOP - MeritCare Hospital, Fargo, North Dakota 58122, United States

MeritCare Broadway, Fargo, North Dakota 58122, United States

Aultman Cancer Center at Aultman Hospital, Canton, Ohio 44710-1799, United States

Mercy Cancer Center at Mercy Medical Center, Canton, Ohio 44708, United States

Jewish Hospital Cancer Center, Cincinnati, Ohio 45236, United States

St. Rita's Medical Center, Lima, Ohio 45801, United States

Geisinger Cancer Institute at Geisinger Health, Danville, Pennsylvania 17822-0001, United States

Penn State Cancer Institute at Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033-0850, United States

Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania 19104-4283, United States

Fox Chase Cancer Center - Philadelphia, Philadelphia, Pennsylvania 19111-2497, United States

UPMC Cancer Centers, Pittsburgh, Pennsylvania 15232, United States

Geisinger Medical Group - Scenery Park, State College, Pennsylvania 16801, United States

Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center, Wilkes-Barre, Pennsylvania 18711, United States

Vanderbilt-Ingram Cancer Center, Nashville, Tennessee 37232-6838, United States

Virginia Commonwealth University Massey Cancer Center, Richmond, Virginia 23298-0037, United States

Marshfield Clinic Cancer Care at Regional Cancer Center, Eau Claire, Wisconsin 54701, United States

Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center, La Crosse, Wisconsin 54601, United States

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, Madison, Wisconsin 53792-6164, United States

Marshfield Clinic - Marshfield Center, Marshfield, Wisconsin 54449, United States

Saint Joseph's Hospital, Marshfield, Wisconsin 54449, United States

Ministry Medical Group at Saint Mary's Hospital, Rhinelander, Wisconsin 54501, United States

Marshfield Clinic - Weston Center, Weston, Wisconsin 54476, United States

Welch Cancer Center at Sheridan Memorial Hospital, Sheridan, Wyoming 82801, United States

Additional Information

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: December 2002
Last updated: January 10, 2013

Page last updated: August 23, 2015

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