MedPath

Melphalan and Dexamethasone With or Without Bortezomib in Treating Patients With Previously Untreated Systemic Light-Chain Amyloidosis

Phase 3
Completed
Conditions
Light Chain Deposition Disease
Primary Systemic Amyloidosis
Interventions
Registration Number
NCT01078454
Lead Sponsor
National Cancer Institute (NCI)
Brief Summary

This randomized phase III trial is studying melphalan and dexamethasone to see how well they work with or without bortezomib in treating patients with previously untreated systemic amyloidosis. Drugs used in chemotherapy, such as melphalan and dexamethasone, work in different ways to stop the growth of plasma cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of plasma cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving melphalan together with dexamethasone is more effective with or without bortezomib in treating systemic amyloidosis.

Detailed Description

PRIMARY OBJECTIVES:

I. To compare hematologic overall response (partial response \[PR\], very good PR, amyloid complete hematologic response \[ACR\], and stringent complete response \[sCR\]) after 3 courses of therapy in patients with previously untreated systemic light-chain amyloidosis treated with melphalan and dexamethasone with vs without bortezomib.

SECONDARY OBJECTIVES:

I. To evaluate the ACR rate after 3 courses of therapy and at completion of therapy.

II. To evaluate organ response rates after 3 courses of therapy and at 6, 9, and 12 months.

III. To evaluate treatment-related mortality.

IV. To evaluate toxicity.

V. To evaluate progression-free and overall survival.

VI. To evaluate PR or better at completion of therapy.

VII. To evaluate time to hematologic and organ response.

VIII. To evaluate the duration of hematologic and organ response.

IX. To assess quality of life (QOL) at baseline, at 3, 6, and 9 months during the therapy, at completion of therapy, and 3 and 6 months after therapy.

TERTIARY OBJECTIVES:

I. To determine the prognostic impact of t(11;14) translocation and cyclin D1 overexpression on response and overall survival.

II. (Correlative) To compare sCR rates and to determine the impact of sCR on the outcomes.

III. (Correlative) To perform a descriptive analysis of amyloid typing and proteomic composition of amyloid tissues.

OUTLINE: This is a multicenter study. Patients are stratified according to amyloid cardiac stage (stage I/II vs. better risk stage III) and are randomized to 1 of 2 treatment arms.

ARM A (Mel-Dex): Patients receive melphalan 0.22 mg/kg orally (PO) and dexamethasone 40 mg PO on days 1-4 every 4 weeks. Treatment repeats every 4 weeks for up to 9 courses in the absence of disease progression or unacceptable toxicity.

ARM B (B-Mel-Dex): Patients receive melphalan 0.22 mg/kg PO and dexamethasone 40 mg PO on days 1-4 and bortezomib 1.3 mg/m2 intravenously (IV) on days 1, 4, 8, and 11 every 4 weeks. Treatment repeats every 4 weeks for 2 cycles. Patients then receive melphalan PO and dexamethasone PO on days 1-4 and bortezomib IV on days 1, 8, 15, and 22 every 5 weeks. Treatment repeats every 5 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Blood, urine, bone marrow, and fat samples may be collected periodically for laboratory analysis. Health-related quality of life is assessed periodically before, during, and after therapy. After completion of study treatment, patients are followed up periodically for 5 years.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
11
Inclusion Criteria
  • Histologically confirmed diagnosis of systemic light-chain amyloidosis

    • Histologic diagnosis of disease must be confirmed by pathology (positive Congo red stain with green birefringence on polarized light microscopy)
    • Genetic testing must be negative for transthyretin mutations associated with hereditary amyloidosis (required in patients who are African-American or who present with peripheral neuropathy as the dominant organ involvement)
  • Measurable disease, defined by >= 1 of the following:

    • Serum M-protein >= 1 g/dL by serum protein electrophoresis (SPEP)
    • Difference between involved and uninvolved free light chain be >4.0mg/dL provided the kappa to lambda free light chain (FLC) ratio is abnormal
  • Symptomatic organ involvement* (heart, kidney, liver/gastrointestinal tract, peripheral nervous system, or soft tissue), defined as any of the following:

    • NOTE: *Carpal tunnel syndrome skin purpura or the presence of vascular amyloid on a bone marrow biopsy alone are not sufficient to meet criteria for "symptomatic organ involvement"
    • Renal involvement is defined as proteinuria (predominantly albumin) > 0.5 g/day by 24-hour urine collection
    • Cardiac involvement is defined as the presence of a mean left ventricular wall thickness of > 12 mm by echocardiogram in the absence of a history of hypertension or valvular heart disease or in the presence of unexplained low voltage (< 0.5 mV) by electrocardiogram
    • Hepatic involvement is defined as hepatomegaly or an alkaline phosphatase > 1.5 times upper limit of normal (ULN)
    • Peripheral nerve involvement is defined by clinical history or abnormal sensory and/or motor findings on neurologic exam
    • Gastrointestinal (GI) involvement is defined as gross GI bleeding or diarrhea (at least 4 stools per day over baseline); a positive GI biopsy is not sufficient to document clinical involvement
    • Autonomic nerve involvement is defined as orthostasis, symptoms of nausea or dysgeusia, gastric atony by gastric emptying scan, diarrhea, or constipation
    • Soft tissue and lymphatic involvement may be ascertained based on classic physical exam findings (macroglossia, shoulder pad sign, raccoon eyes, carpal tunnel syndrome, synovial enlargement, firm enlarged lymph nodes) or biopsy
  • Ineligible for autologous stem cell transplantation with melphalan 200 mg/m^2 or refuses to undergo transplantation

  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2

  • Amyloid cardiac biomarker stage I or II disease

    • The amyloid cardiac staging system is based on NT-proBNP and troponin-T levels. If troponin T (cTnT) is not available at local institution then troponin I (cTnI) may be used. Thresholds for cTnT, cTnI, and NT-proBNP are < 0.035 ug/L, < 0.1 ug/L, and < 332 ng/L, respectively. Stage I patients have both troponin-T (or I) and NT-proBNP below the threshold. Stage II patients have either troponin-T (I) or NT-proBNP above the threshold. Stage III patients have troponin-T (or I) and simultaneous NT-proBNP above the threshold. Stage III patients are further classified as "better risk" if NT-proBNP is over 332 ng/L but less than 6000 ng/L
  • Negative pregnancy test

  • Fertile patients must use effective contraception

  • The absence of supine systolic blood pressure < 100 mmHg and difficult to manage symptomatic orthostatic hypotension

  • Absolute neutrophil count (ANC) > 1,500/mm^3

  • Platelet count > 140,000/mm^3

  • Hemoglobin > 10 g/dL

  • Total bilirubin < 2.5 mg/dL

  • Alkaline phosphatase < 5 times upper limit of normal (ULN)

  • Aspartate aminotransferase (AST) < 3 times ULN

  • Creatinine clearance > 30 mL/min

  • Bone marrow plasma cells < 30%

  • Human immunodeficiency virus (HIV)-positivity allowed provided the following criteria are met:

    • No history of acquired immunodeficiency syndrome (AIDS)-defining events including history of CD4 cell count < 200/mm^3
    • Current CD4 cell count >= 350/mm^3
    • Not receiving zidovudine or stavudine
    • No secondary amyloidosis
  • More than 3 weeks since radiotherapy

    • Enrollment of subjects who require radiotherapy (which must be localized in field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy
  • More than 14 days since prior and no concurrent participation in clinical trials with other investigational agents not included in this trial

Exclusion Criteria
  • Pregnant or nursing
  • Clinically overt myeloma (hypercalcemia or lytic bone lesions)
  • Prior chemotherapy or radiotherapy for the treatment of myeloma or systemic light-chain amyloidosis
  • History of sustained ventricular tachycardias
  • Cardiac syncope
  • Uncompensated New York Heart Association (NYHA) class III or IV congestive heart failure
  • Uncontrolled infection
  • Active malignancy within the past 5 years except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or adequately treated stage I cancer currently in complete remission
  • Serious medical or psychiatric illness likely to interfere with study participation, including recent myocardial infarction (within the past 6 months) or poorly controlled diabetes mellitus
  • Hypersensitivity to bortezomib, boron, or mannitol
  • Grade 2 or higher peripheral neuropathy

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ARM A (Mel-Dex)melphalanPatients receive melphalan 0.22 mg/kg orally (PO) and dexamethasone 40 mg PO on days 1-4 every 4 weeks. Treatment repeats every 4 weeks for up to 9 courses in the absence of disease progression or unacceptable toxicity.
ARM A (Mel-Dex)dexamethasonePatients receive melphalan 0.22 mg/kg orally (PO) and dexamethasone 40 mg PO on days 1-4 every 4 weeks. Treatment repeats every 4 weeks for up to 9 courses in the absence of disease progression or unacceptable toxicity.
ARM B (B-Mel-Dex)melphalanPatients receive melphalan 0.22 mg/kg PO and dexamethasone 40 mg PO on days 1-4 and bortezomib 1.3 mg/m\^2 intravenously (IV) on days 1, 4, 8, and 11 every 4 weeks. Treatment repeats every 4 weeks for 2 cycles. Patients then receive melphalan PO and dexamethasone PO on days 1-4 and bortezomib IV on days 1, 8, 15, and 22 every 5 weeks. Treatment repeats every 5 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
ARM B (B-Mel-Dex)bortezomibPatients receive melphalan 0.22 mg/kg PO and dexamethasone 40 mg PO on days 1-4 and bortezomib 1.3 mg/m\^2 intravenously (IV) on days 1, 4, 8, and 11 every 4 weeks. Treatment repeats every 4 weeks for 2 cycles. Patients then receive melphalan PO and dexamethasone PO on days 1-4 and bortezomib IV on days 1, 8, 15, and 22 every 5 weeks. Treatment repeats every 5 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
ARM B (B-Mel-Dex)dexamethasonePatients receive melphalan 0.22 mg/kg PO and dexamethasone 40 mg PO on days 1-4 and bortezomib 1.3 mg/m\^2 intravenously (IV) on days 1, 4, 8, and 11 every 4 weeks. Treatment repeats every 4 weeks for 2 cycles. Patients then receive melphalan PO and dexamethasone PO on days 1-4 and bortezomib IV on days 1, 8, 15, and 22 every 5 weeks. Treatment repeats every 5 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
Primary Outcome Measures
NameTimeMethod
Proportion of Patients With Hematologic Overall Response (Partial Response [PR]+ Very Good PR [VGPR]+ Amyloid Complete Response [ACR]+ Stringent Complete Response [sCR]) After 3 Months (3 Cycles) of TherapyAssessed at 3 months

sCR: ACR and no clonal cells in bone marrow (BM) ACR: Negative serum/urine immunofixation (IF), \<5% plasma cells in BM, and normal serum FLC ratio VGPR: 1. PR and any of the following; 2. serum/urine M-protein detectable by IF but not measurable (NM) on electrophoresis (EP); (3) ≥90% reduction in serum M-component and urine M-protein \<100 mg/24 hr if baseline serum measurable; (4) urine M-component \<100 mg/24 hr and NM serum M-protein on serum protein EP if baseline urine measurable; (5) ≥90% drop in the difference between involved and uninvolved FLC levels if only FLC measurable PR: (1) ≥50% drop of serum M-protein and 24-hr urinary M-protein drop by ≥90% or to \<200 mg/24 hr if baseline serum/urine measurable; or (2) ≥50% drop of serum M-protein if only serum measurable at baseline; or (3) 24-hr urinary M-protein drop by ≥90% or to \<200 mg/24 hr if baseline urine measurable; or (4) ≥ 50% drop in the difference between involved and uninvolved FLC if only FLC measu

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (209)

Illinois CancerCare-Canton

🇺🇸

Canton, Illinois, United States

Illinois CancerCare-Carthage

🇺🇸

Carthage, Illinois, United States

Emory University/Winship Cancer Institute

🇺🇸

Atlanta, Georgia, United States

Eureka Hospital

🇺🇸

Eureka, Illinois, United States

Illinois CancerCare Galesburg

🇺🇸

Galesburg, Illinois, United States

Bronson Methodist Hospital

🇺🇸

Kalamazoo, Michigan, United States

Memorial Hospital

🇺🇸

Carthage, Illinois, United States

Decatur Memorial Hospital

🇺🇸

Decatur, Illinois, United States

Mason District Hospital

🇺🇸

Havana, Illinois, United States

Mcdonough District Hospital

🇺🇸

Macomb, Illinois, United States

Great Falls Clinic

🇺🇸

Great Falls, Montana, United States

Marshfield Clinic - Weston Center

🇺🇸

Weston, Wisconsin, United States

Upper Valley Medical Center

🇺🇸

Troy, Ohio, United States

Clackamas Radiation Oncology Center

🇺🇸

Clackamas, Oregon, United States

Green Bay Oncology - Oconto Falls

🇺🇸

Oconto Falls, Wisconsin, United States

Waukesha Memorial Hospital - ProHealth Care

🇺🇸

Waukesha, Wisconsin, United States

Diagnostic and Treatment Center

🇺🇸

Weston, Wisconsin, United States

Marshfield Clinic Cancer Care at Saint Michael's Hospital

🇺🇸

Stevens Point, Wisconsin, United States

Boston Medical Center

🇺🇸

Boston, Massachusetts, United States

Minor and James Medical PLLC

🇺🇸

Seattle, Washington, United States

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

🇺🇸

Seattle, Washington, United States

Group Health Cooperative-Seattle

🇺🇸

Seattle, Washington, United States

Indiana University Medical Center

🇺🇸

Indianapolis, Indiana, United States

Illinois CancerCare-Peru

🇺🇸

Peru, Illinois, United States

Illinois Valley Hospital

🇺🇸

Peru, Illinois, United States

Washington University School of Medicine

🇺🇸

Saint Louis, Missouri, United States

MetroHealth Medical Center

🇺🇸

Cleveland, Ohio, United States

Greene Memorial Hospital

🇺🇸

Xenia, Ohio, United States

Geisinger Medical Center-Cancer Center Hazelton

🇺🇸

Hazleton, Pennsylvania, United States

PeaceHealth Saint Joseph Medical Center

🇺🇸

Bellingham, Washington, United States

Highline Medical Center-Main Campus

🇺🇸

Burien, Washington, United States

Swedish Cancer Institute-Issaquah

🇺🇸

Issaquah, Washington, United States

Cancer Care Northwest - Spokane South

🇺🇸

Spokane, Washington, United States

The Polyclinic

🇺🇸

Seattle, Washington, United States

United General Hospital

🇺🇸

Sedro-Woolley, Washington, United States

University of Washington Medical Center

🇺🇸

Seattle, Washington, United States

PeaceHealth Southwest Medical Center

🇺🇸

Vancouver, Washington, United States

Compass Oncology Vancouver

🇺🇸

Vancouver, Washington, United States

Wenatchee Valley Medical Center

🇺🇸

Wenatchee, Washington, United States

Tufts Medical Center

🇺🇸

Boston, Massachusetts, United States

Fox Chase Cancer Center

🇺🇸

Philadelphia, Pennsylvania, United States

Hutchinson Area Health Care

🇺🇸

Hutchinson, Minnesota, United States

Rice Memorial Hospital

🇺🇸

Willmar, Minnesota, United States

Abbott-Northwestern Hospital

🇺🇸

Minneapolis, Minnesota, United States

Ridgeview Medical Center

🇺🇸

Waconia, Minnesota, United States

Minnesota Oncology and Hematology PA-Woodbury

🇺🇸

Woodbury, Minnesota, United States

Minnesota Oncology Hematology PA-Maplewood

🇺🇸

Maplewood, Minnesota, United States

Penrose-Saint Francis Healthcare

🇺🇸

Colorado Springs, Colorado, United States

Castle Medical Center

🇺🇸

Kailua, Hawaii, United States

Wilcox Memorial Hospital and Kauai Medical Clinic

🇺🇸

Lihue, Hawaii, United States

Pali Momi Medical Center

🇺🇸

'Aiea, Hawaii, United States

Saint Anthony Hospital

🇺🇸

Lakewood, Colorado, United States

Boulder Community Hospital

🇺🇸

Boulder, Colorado, United States

Littleton Adventist Hospital

🇺🇸

Littleton, Colorado, United States

Parker Adventist Hospital

🇺🇸

Parker, Colorado, United States

Swedish Medical Center

🇺🇸

Englewood, Colorado, United States

Oncare Hawaii Inc-Pali Momi

🇺🇸

'Aiea, Hawaii, United States

Exempla Lutheran Medical Center

🇺🇸

Wheat Ridge, Colorado, United States

University of Mississippi Medical Center

🇺🇸

Jackson, Mississippi, United States

Graham Hospital Association

🇺🇸

Canton, Illinois, United States

Porter Adventist Hospital

🇺🇸

Denver, Colorado, United States

Presbyterian - Saint Lukes Medical Center - Health One

🇺🇸

Denver, Colorado, United States

Exempla Saint Joseph Hospital

🇺🇸

Denver, Colorado, United States

Rose Medical Center

🇺🇸

Denver, Colorado, United States

Colorado Cancer Research Program CCOP

🇺🇸

Denver, Colorado, United States

Wayne State University/Karmanos Cancer Institute

🇺🇸

Detroit, Michigan, United States

Providence Portland Medical Center

🇺🇸

Portland, Oregon, United States

Western Oncology Research Consortium

🇺🇸

Portland, Oregon, United States

Adventist Medical Center

🇺🇸

Portland, Oregon, United States

Providence Saint Vincent Medical Center

🇺🇸

Portland, Oregon, United States

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

Saint Luke's Regional Medical Center

🇺🇸

Sioux City, Iowa, United States

Union Hospital of Cecil County

🇺🇸

Elkton, Maryland, United States

Borgess Medical Center

🇺🇸

Kalamazoo, Michigan, United States

Green Bay Oncology - Iron Mountain

🇺🇸

Iron Mountain, Michigan, United States

Fairview-Southdale Hospital

🇺🇸

Edina, Minnesota, United States

Mercy Hospital

🇺🇸

Coon Rapids, Minnesota, United States

Metro-Minnesota CCOP

🇺🇸

Saint Louis Park, Minnesota, United States

Unity Hospital

🇺🇸

Fridley, Minnesota, United States

New Ulm Medical Center

🇺🇸

New Ulm, Minnesota, United States

Saint John's Hospital - Healtheast

🇺🇸

Maplewood, Minnesota, United States

Hennepin County Medical Center

🇺🇸

Minneapolis, Minnesota, United States

Regions Hospital

🇺🇸

Saint Paul, Minnesota, United States

Saint Francis Regional Medical Center

🇺🇸

Shakopee, Minnesota, United States

North Memorial Medical Health Center

🇺🇸

Robbinsdale, Minnesota, United States

Park Nicollet Clinic - Saint Louis Park

🇺🇸

Saint Louis Park, Minnesota, United States

Lakeview Hospital

🇺🇸

Stillwater, Minnesota, United States

United Hospital

🇺🇸

Saint Paul, Minnesota, United States

Benefis Healthcare- Sletten Cancer Institute

🇺🇸

Great Falls, Montana, United States

Kalispell Medical Oncology

🇺🇸

Kalispell, Montana, United States

Case Western Reserve University

🇺🇸

Cleveland, Ohio, United States

Montana Cancer Specialists

🇺🇸

Missoula, Montana, United States

Blanchard Valley Hospital

🇺🇸

Findlay, Ohio, United States

Clinton Memorial Hospital

🇺🇸

Wilmington, Ohio, United States

Atrium Medical Center-Middletown Regional Hospital

🇺🇸

Franklin, Ohio, United States

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

🇺🇸

Columbus, Ohio, United States

The Jewish Hospital

🇺🇸

Cincinnati, Ohio, United States

Wayne Hospital

🇺🇸

Greenville, Ohio, United States

Providence Milwaukie Hospital

🇺🇸

Milwaukie, Oregon, United States

Geisinger Medical Center

🇺🇸

Danville, Pennsylvania, United States

Cancer Care Center at Island Hospital

🇺🇸

Anacortes, Washington, United States

Geisinger Medical Group

🇺🇸

State College, Pennsylvania, United States

Geisinger Wyoming Valley

🇺🇸

Wilkes-Barre, Pennsylvania, United States

Harrison HealthPartners Hematology and Oncology-Bremerton

🇺🇸

Bremerton, Washington, United States

Harborview Medical Center

🇺🇸

Seattle, Washington, United States

Swedish Medical Center-First Hill

🇺🇸

Seattle, Washington, United States

Columbia Basin Hematology and Oncology PLLC

🇺🇸

Kennewick, Washington, United States

Harrison HealthPartners Hematology and Oncology-Poulsbo

🇺🇸

Poulsbo, Washington, United States

Green Bay Oncology Limited at Saint Mary's Hospital

🇺🇸

Green Bay, Wisconsin, United States

Skagit Valley Hospital

🇺🇸

Mount Vernon, Washington, United States

Marshfield Clinic-Chippewa Center

🇺🇸

Chippewa Falls, Wisconsin, United States

Marshfield Clinic Cancer Center at Sacred Heart

🇺🇸

Eau Claire, Wisconsin, United States

Green Bay Oncology at Saint Vincent Hospital

🇺🇸

Green Bay, Wisconsin, United States

Gundersen Lutheran

🇺🇸

La Crosse, Wisconsin, United States

Saint Mary's Hospital

🇺🇸

Green Bay, Wisconsin, United States

Holy Family Memorial Hospital

🇺🇸

Manitowoc, Wisconsin, United States

Marshfield Clinic-Minocqua Center

🇺🇸

Minocqua, Wisconsin, United States

D N Greenwald Center

🇺🇸

Mukwonago, Wisconsin, United States

Rocky Mountain Oncology

🇺🇸

Casper, Wyoming, United States

Welch Cancer Center

🇺🇸

Sheridan, Wyoming, United States

Green Bay Oncology - Sturgeon Bay

🇺🇸

Sturgeon Bay, Wisconsin, United States

The Medical Center of Aurora

🇺🇸

Aurora, Colorado, United States

University of Michigan

🇺🇸

Ann Arbor, Michigan, United States

Fairview Ridges Hospital

🇺🇸

Burnsville, Minnesota, United States

Oncare Hawaii Inc-Kuakini

🇺🇸

Honolulu, Hawaii, United States

Oncare Hawaii Inc-POB II

🇺🇸

Honolulu, Hawaii, United States

North Colorado Medical Center

🇺🇸

Greeley, Colorado, United States

Sky Ridge Medical Center

🇺🇸

Lone Tree, Colorado, United States

McKee Medical Center

🇺🇸

Loveland, Colorado, United States

Cleveland Clinic Florida - Weston

🇺🇸

Weston, Florida, United States

Longmont United Hospital

🇺🇸

Longmont, Colorado, United States

Saint Mary Corwin Medical Center

🇺🇸

Pueblo, Colorado, United States

Eastern Connecticut Hematology and Oncology Associates

🇺🇸

Norwich, Connecticut, United States

North Suburban Medical Center

🇺🇸

Thornton, Colorado, United States

Beebe Medical Center

🇺🇸

Lewes, Delaware, United States

Christiana Care Health System-Christiana Hospital

🇺🇸

Newark, Delaware, United States

Mayo Clinic in Florida

🇺🇸

Jacksonville, Florida, United States

Illinois CancerCare-Bloomington

🇺🇸

Bloomington, Illinois, United States

Saint Joseph Medical Center

🇺🇸

Bloomington, Illinois, United States

Illinois CancerCare-Eureka

🇺🇸

Eureka, Illinois, United States

Illinois CancerCare-Havana

🇺🇸

Havana, Illinois, United States

Illinois CancerCare-Kewanee Clinic

🇺🇸

Kewanee, Illinois, United States

Holy Family Medical Center

🇺🇸

Monmouth, Illinois, United States

Illinois CancerCare-Macomb

🇺🇸

Macomb, Illinois, United States

Illinois CancerCare-Monmouth

🇺🇸

Monmouth, Illinois, United States

Bromenn Regional Medical Center

🇺🇸

Normal, Illinois, United States

Illinois CancerCare-Ottawa Clinic

🇺🇸

Ottawa, Illinois, United States

Ottawa Regional Hospital and Healthcare Center

🇺🇸

Ottawa, Illinois, United States

Community Cancer Center Foundation

🇺🇸

Normal, Illinois, United States

Illinois CancerCare-Community Cancer Center

🇺🇸

Normal, Illinois, United States

Illinois CancerCare-Pekin

🇺🇸

Pekin, Illinois, United States

Proctor Hospital

🇺🇸

Peoria, Illinois, United States

Methodist Medical Center of Illinois

🇺🇸

Peoria, Illinois, United States

Illinois Oncology Research Association CCOP

🇺🇸

Peoria, Illinois, United States

Illinois CancerCare-Peoria

🇺🇸

Peoria, Illinois, United States

OSF Saint Francis Medical Center

🇺🇸

Peoria, Illinois, United States

Illinois CancerCare-Princeton

🇺🇸

Princeton, Illinois, United States

Pekin Cancer Treatment Center

🇺🇸

Pekin, Illinois, United States

Perry Memorial Hospital

🇺🇸

Princeton, Illinois, United States

Saint Francis Hospital and Health Centers

🇺🇸

Beech Grove, Indiana, United States

Illinois CancerCare-Spring Valley

🇺🇸

Spring Valley, Illinois, United States

McFarland Clinic PC-William R Bliss Cancer Center

🇺🇸

Ames, Iowa, United States

Reid Hospital and Health Care Services

🇺🇸

Richmond, Indiana, United States

Memorial Medical Center

🇺🇸

Springfield, Illinois, United States

University of Iowa Hospitals and Clinics

🇺🇸

Iowa City, Iowa, United States

Mercy Medical Center-Sioux City

🇺🇸

Sioux City, Iowa, United States

Siouxland Hematology Oncology Associates

🇺🇸

Sioux City, Iowa, United States

Kettering Medical Center

🇺🇸

Kettering, Ohio, United States

Kalispell Regional Medical Center

🇺🇸

Kalispell, Montana, United States

Bozeman Deaconess Hospital

🇺🇸

Bozeman, Montana, United States

Cooper Hospital University Medical Center

🇺🇸

Camden, New Jersey, United States

West Michigan Cancer Center

🇺🇸

Kalamazoo, Michigan, United States

University of Arkansas for Medical Sciences

🇺🇸

Little Rock, Arkansas, United States

Mayo Clinic in Arizona

🇺🇸

Scottsdale, Arizona, United States

Saint Patrick Hospital - Community Hospital

🇺🇸

Missoula, Montana, United States

Glacier Oncology PLLC

🇺🇸

Kalispell, Montana, United States

Providence Hospital

🇺🇸

Southfield, Michigan, United States

Saint James Community Hospital and Cancer Treatment Center

🇺🇸

Butte, Montana, United States

Montana Cancer Consortium CCOP

🇺🇸

Billings, Montana, United States

Green Bay Oncology - Escanaba

🇺🇸

Escanaba, Michigan, United States

Saint Vincent Healthcare

🇺🇸

Billings, Montana, United States

Hematology-Oncology Centers of the Northern Rockies PC

🇺🇸

Billings, Montana, United States

Billings Clinic

🇺🇸

Billings, Montana, United States

Bozeman Deaconess Cancer Center

🇺🇸

Bozeman, Montana, United States

Saint Peter's Community Hospital

🇺🇸

Helena, Montana, United States

Northern Montana Hospital

🇺🇸

Havre, Montana, United States

Providence Newberg Medical Center

🇺🇸

Newberg, Oregon, United States

Saint Vincent Hospital

🇺🇸

Green Bay, Wisconsin, United States

Saint Nicholas Hospital

🇺🇸

Sheboygan, Wisconsin, United States

Marshfield Clinic - Wisconsin Rapids Center

🇺🇸

Wisconsin Rapids, Wisconsin, United States

Providence Willamette Falls Medical Center

🇺🇸

Oregon City, Oregon, United States

Marshfield Clinic at James Beck Cancer Center

🇺🇸

Rhinelander, Wisconsin, United States

Bay Area Medical Center

🇺🇸

Marinette, Wisconsin, United States

Marshfield Clinic

🇺🇸

Marshfield, Wisconsin, United States

Marshfield Clinic-Rice Lake Center

🇺🇸

Rice Lake, Wisconsin, United States

Oconomowoc Memorial Hospital-ProHealth Care Inc

🇺🇸

Oconomowoc, Wisconsin, United States

Straub Clinic and Hospital

🇺🇸

Honolulu, Hawaii, United States

University of Hawaii

🇺🇸

Honolulu, Hawaii, United States

Queen's Medical Center

🇺🇸

Honolulu, Hawaii, United States

Kuakini Medical Center

🇺🇸

Honolulu, Hawaii, United States

OnCare Hawaii-Liliha

🇺🇸

Honolulu, Hawaii, United States

Kapiolani Medical Center for Women and Children

🇺🇸

Honolulu, Hawaii, United States

Grandview Hospital

🇺🇸

Dayton, Ohio, United States

Samaritan North Health Center

🇺🇸

Dayton, Ohio, United States

Dayton CCOP

🇺🇸

Dayton, Ohio, United States

Good Samaritan Hospital - Dayton

🇺🇸

Dayton, Ohio, United States

Miami Valley Hospital

🇺🇸

Dayton, Ohio, United States

Evergreen Hematology and Oncology PS

🇺🇸

Spokane, Washington, United States

Saint Mary's Hospital and Regional Medical Center

🇺🇸

Grand Junction, Colorado, United States

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