Combination Chemotherapy With or Without Monoclonal Antibody Therapy in Treating Patients With AML Leukemia
Status: | Active, not recruiting |
---|---|
Conditions: | Blood Cancer, Leukemia |
Therapuetic Areas: | Oncology |
Healthy: | No |
Age Range: | 16 - 60 |
Updated: | 1/16/2019 |
Start Date: | December 2002 |
End Date: | January 2019 |
A Phase III Trial in Adult Acute Myeloid Leukemia: Daunorubicin Dose-Intensification Prior to Risk-Allocated Autologous Stem Cell Transplantation
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.
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.
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.
- 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.
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
We found this trial at
99
sites
8915 W Golf Rd
Niles, Illinois 60714
Niles, Illinois 60714
(847) 827-9060

Cancer Care and Hematology Specialists of Chicagoland - Niles Illinois Cancer Specialists is dedicated to...
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1300 Morris Park Avenue
Bronx, New York 10461
Bronx, New York 10461
718.430.2302

Albert Einstein Cancer Center at Albert Einstein College of Medicine The Albert Einstein Cancer Center...
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Aultman Cancer Center at Aultman Hospital Serving Stark and surrounding counties since 1892, Aultman Hospital...
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675 N Saint Clair St # 21-100
Chicago, Illinois 60611
Chicago, Illinois 60611
(312) 695-1156

Robert H. Lurie Comprehensive Cancer Center at Northwestern University The cancer center was first established...
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100 North Academy Ave
Danville, Pennsylvania 17822
Danville, Pennsylvania 17822
570-271-6211

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1719 East 19th Avenue
Denver, Colorado 80218
Denver, Colorado 80218
(303) 839-6000

Presbyterian - St. Luke's Medical Center Presbyterian/St. Luke's Medical Center and the Rocky Mountain Hospital...
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11143 Parkview Plaza Dr # 100
Fort Wayne, Indiana 46845
Fort Wayne, Indiana 46845
(260) 484-8830

Fort Wayne Medical Oncology and Hematology Fort Wayne Medical Oncology and Hematology provides state-of-the-art cancer...
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1376 Mowry Road
Gainesville, Florida 32610
Gainesville, Florida 32610
(352) 273-8010

University of Florida Shands Cancer Center We are the University of Florida Health Cancer Center
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West Michigan Cancer Center In 1994, Borgess Health Alliance and Bronson Healthcare Group opened the...
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Bronson Methodist Hospital Our healthcare system serves patients and families throughout southwest Michigan and northern...
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Vanderbilt-Ingram Cancer Center The Vanderbilt-Ingram Cancer Center, located in Nashville, Tenn., brings together the clinical...
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401 College Street
Richmond, Virginia 23298
Richmond, Virginia 23298
(804) 828-0450

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1365 Clifton Rd NE
Atlanta, Georgia 30322
Atlanta, Georgia 30322
(404) 778-1900

Winship Cancer Institute at Emory University Winship Cancer Institute of Emory University is Georgia
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Aurora Presbyterian Hospital At The Medical Center of Aurora and Centennial Medical Plaza, we treat...
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MeritCare Bemidji Sanford Health is an integrated health system headquartered in the Dakotas and is...
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2900 12th Ave N Ste 160W
Billings, Montana 59101
Billings, Montana 59101
(406) 238-6290

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1101 N 27th St # 201
Billings, Montana 59101
Billings, Montana 59101
(406) 237-3585

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Birmingham, Alabama 35294
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Boca Raton, Florida 33428
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Boca Raton, Florida 33486
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Bozeman Deaconess Cancer Center Bozeman Deaconess Cancer Center provides the latest cancer technologies and treatment...
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Fairview Ridges Hospital Fairview Ridges Hospital is a 150-bed, Level III Trauma Care facility, offering...
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St. James Healthcare Cancer Care The St. James Cancer Center is an integrated cancer treatment...
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Hematology and Oncology Associates Northwestern Medical Faculty Foundation (the Foundation) is a premier, multi-specialty physician...
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2222 N. Nevada Avenue
Colorado Springs, Colorado 80907
Colorado Springs, Colorado 80907
(719) 776-5000

Penrose Cancer Center at Penrose Hospital Through a full range of clinical trials, genetic counseling,...
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11850 Blackfoot St. NW
Suite 130
Coon Rapids, Minnesota 55433
Coon Rapids, Minnesota 55433
763-236-0808

Mercy and Unity Cancer Center at Mercy Hospital The Virginia Piper Cancer Institute - Mercy...
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St. Anthony Central Hospital The St. Anthony Medical Campus in Lakewood combines our heritage of...
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Porter Adventist Hospital Founded in 1930, Porter Adventist Hospital has provided people throughout Denver and...
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Rose Medical Center Well known as a Denver institution and a 9th Avenue landmark for...
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Fairview Southdale Hospital Fairview Health Services is an award-winning nonprofit health care system based in...
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CCOP - MeritCare Hospital The Sanford Community Cancer Consortium is a "newly" formed CCOP, merging...
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550 Osborne Road
Fridley, Minnesota 55432
Fridley, Minnesota 55432
763-236-5000

Mercy and Unity Cancer Center at Unity Hospital Patients and their families are the heart...
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2635 North 7th Street
Grand Junction, Colorado 81501
Grand Junction, Colorado 81501
970-298-CARE (2273)
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St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center St. Mary's Hospital...
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Great Falls Clinic Founded in 1917, the Great Falls Clinic is the fourth oldest medical...
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North Colorado Medical Center NCMC is a fully accredited, private, non-profit facility licensed to operate...
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St. Peter's Hospital Welcome to St. Peter’s Hospital, providing premier health care to a five–county...
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535 Barnhill Dr
Indianapolis, Indiana 46202
Indianapolis, Indiana 46202
(888) 600-4822

Indiana University Melvin and Bren Simon Cancer Center At the IU Simon Cancer Center, more...
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Borgess Medical Center At Borgess, healing is our calling. This is the place where people...
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Glacier Oncology, PLLC Glacier Oncology are physician clinics focusing exclusively on the medical subspecialties of...
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Kalispell Medical Oncology at KRMC Our commitment to integrating modern treatment programs with highly-trained physicians...
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Kalispell Regional Medical Center Nestled in the beautiful Flathead Valley of Northwestern Montana, Kalispell Regional...
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1800 Hollister Drive, Suite 112
Libertyville, Illinois 60048
Libertyville, Illinois 60048
847-367-6781
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North Shore Oncology and Hematology Associates, Limited - Libertyville Welcome to North Shore Oncology and...
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St. Rita's Medical Center Welcome to St. Rita's Medical Center. As the region's leader in...
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Sky Ridge Medical Center HealthONE is the largest healthcare system in the metro Denver area...
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1950 Mountain View Ave
Longmont, Colorado 80501
Longmont, Colorado 80501
303.651.5111

Hope Cancer Care Center at Longmont United Hospital Patients treated at the Hope Cancer Care...
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McKee Medical Center Through the years, McKee has led the way in health care innovation....
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Marshfield Clinic - Marshfield Center The Clinic was incorporated under Wisconsin law in 1916 and...
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Saint Joseph's Hospital Our Mission as a Catholic health care system is to further the...
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800 E 28th St
Minneapolis, Minnesota 55407
Minneapolis, Minnesota 55407
612-863-4000

Virginia Piper Cancer Institute at Abbott - Northwestern Hospital As the largest hospital in the...
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Montana Cancer Center at St. Patrick Hospital and Health Sciences Center St. Patrick Hospital is...
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160 E 34th St
New York, New York 10016
New York, New York 10016
(212) 731-5001

NYU Cancer Institute at New York University Medical Center The Perlmutter Cancer Center takes a...
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3400 Civic Center Blvd
Philadelphia, Pennsylvania 19104
Philadelphia, Pennsylvania 19104
(215) 662-6065

Abramson Cancer Center of the University of Pennsylvania The Abramson Cancer Center of the University...
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2251 North Shore Drive
Rhinelander, Wisconsin 54501
Rhinelander, Wisconsin 54501
715.361.2000
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Ministry Medical Group at Saint Mary's Hospital Ministry Saint Mary
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Mayo Clinic Cancer Center The Mayo Clinic Cancer Center is a National Cancer Institute-designated comprehensive...
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Park Nicollet Cancer Center Park Nicollet Methodist Hospital has a long and rich history in...
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United Hospital United Hospital is the largest hospital in the Twin Cities east metro area,...
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Mayo Clinic Scottsdale Mayo Clinic Arizona was the second Mayo practice to be established outside...
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200 Scenery Drive
State College, Pennsylvania 16801
State College, Pennsylvania 16801
814-231-4560

Geisinger Medical Group - Scenery Park Geisinger-Scenery Park provides an impressive array of healthcare right...
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North Suburban Medical Center North Suburban Medical Center has established a reputation as a facility...
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CCOP - Carle Cancer Center The Carle Cancer Center Community Clinical Oncology Program (CCOP) in...
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Ridgeview Medical Center Ridgeview Medical Center is an independent, nonprofit, regional health care system located...
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Marshfield Clinic - Weston Center The Clinic was incorporated under Wisconsin law in 1916 and...
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Exempla Lutheran Medical Center Welcome to Exempla Lutheran Medical Center and thank you for choosing...
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1000 E. Mountain Blvd.
Wilkes-Barre, Pennsylvania 18711
Wilkes-Barre, Pennsylvania 18711
570-808-6150

Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center The Frank...
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