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Intergroup Randomized Phase 2 Four Arm Study In Patients ≥ 60 With Previously Untreated Mantle Cell Lymphoma Of Therapy With: Arm A = Rituximab+ Bendamustine Followed By Rituximab Consolidation (RB → R); Arm B = Rituximab + Bendamustine + Bortezomib Followed By Rituximab Consolidation (RBV→ R), Arm C = Rituximab + Bendamustine Followed By Lenalidomide + Rituximab Consolidation (RB → LR) or Arm D = Rituximab + Bendamustine + Bortezomib Followed By Lenalidomide + Rituximab Consolidation (RBV → LR)


Phase 2
60 Years
N/A
Open (Enrolling)
Both
Lymphoma, Neurotoxicity, Therapy-related Toxicity

Thank you

Trial Information

Intergroup Randomized Phase 2 Four Arm Study In Patients ≥ 60 With Previously Untreated Mantle Cell Lymphoma Of Therapy With: Arm A = Rituximab+ Bendamustine Followed By Rituximab Consolidation (RB → R); Arm B = Rituximab + Bendamustine + Bortezomib Followed By Rituximab Consolidation (RBV→ R), Arm C = Rituximab + Bendamustine Followed By Lenalidomide + Rituximab Consolidation (RB → LR) or Arm D = Rituximab + Bendamustine + Bortezomib Followed By Lenalidomide + Rituximab Consolidation (RBV → LR)


OBJECTIVES:

Primary

- To determine whether the addition of bortezomib (RBV) to an induction regimen of
rituximab-bendamustine hydrochloride (RB) improves progression-free survival (PFS)
compared to RB alone in patients ≥ 60 years of age with previously untreated mantle
cell lymphoma.

- To determine whether the addition of lenalidomide to a consolidation regimen of
rituximab following an induction regimen of RB or RBV improves PFS compared to
consolidation rituximab alone in this patient population.

Secondary

- To determine whether the addition of bortezomib to induction therapy improves the
positron emission tomography (PET)-documented complete response (CR) rate compared to
RB alone.

- To determine the objective response rate (ORR) for RB and RBV.

- Among patients who do not have PET-documented CR at the end of induction, to determine
whether the addition of lenalidomide to consolidation therapy improves CR and ORR
compared with rituximab alone.

- To determine overall survival (OS) in the treatment arms.

- To determine safety, with attention to the addition of bortezomib in the induction
regimen and lenalidomide-rituximab (LR) as consolidation therapy.

- To collect paraffin-embedded tissue for creation of tissue microarray.

- To collect and bank serum and blood mononuclear cells for future studies.

- To collect formalin-fixed paraffin-embedded (FFPE) tissue to analyze potential
prognostic factors (Ki-67 proliferation index by immunohistochemistry and correlation
with proposed 5-gene set of proliferation markers analyzed by RNA PCR; SOX 11
expression by immunohistochemistry; and Micro-RNA levels by microarray).

- Using patient-reported outcomes data, to determine the extent and severity of
neuropathy associated with the addition of bortezomib to induction treatment.

- Using patient-reported outcomes data, to determine the extent and severity of fatigue
associated with the addition of lenalidomide to consolidation treatment.

- To evaluate the effects of the addition of bortezomib and lenalidomide on
patient-reported health-related quality of life.

- To evaluate the effects of bortezomib-related neuropathy on patient-reported
health-related quality of life.

- To evaluate the response of lymphoma-specific symptoms to treatment.

- Using longitudinal patient-reported outcomes data, to describe the trajectory of
lymphoma symptoms, neuropathy, fatigue, and overall health-related quality of life
prior to, during, and following treatment among older adults with MCL.

Tertiary

- To assess the proportion of patients up and down staging when fludeoxyglucose F 18-
(FDG) PET/CT is added to standard Ann Arbor staging.

- To assess the ability of pre-treatment FDG-PET/CT (SUVmax) to predict response rate and
PFS.

- Among patients with interim (post-cycle 3) FDG-PET/CT imaging, to assess the
correlation of interim FDG-PET/CT imaging with response rate and PFS both during
induction and consolidation therapy.

- To assess standard FDG-PET/CT metrics including SUVmax, tumor metabolic burden, total
tumor burden, and association with pathology features (blastoid variant vs other, and
Ki67) in the setting of MCL.

- To assess differences in overall and CR rates when using Deauville vs International
Harmonization Project FDG-PET/CT interpretation criteria.

- To determine whether there is a correlation between FDG-PET/CT response and residual
disease assessment by molecular and/or flow cytometric techniques.

- To determine whether the number of malignant cells in circulation predict the number of
cells in marrow.

- To determine whether the number of malignant cells in circulation/in marrow at the end
of induction correlate with CR and 2-year PFS.

- To determine whether there is a higher rate of minimal residual disease (MRD)
negativity among patients randomized to RBV as compared with RB, and among patients
treated with LR maintenance compared with rituximab.

- To compare the two methods of MRD detection - molecular techniques and flow cytometry -
as prognostic markers for outcome.

OUTLINE: This is a multicenter study. Patients are stratified according to mantle cell
lymphoma International Prognostic Index risk score (low vs intermediate vs high). Patients
are randomized to 1 of 4 treatment arms.

- Arm A: Patients receive induction therapy comprising rituximab IV on day 1 and
bendamustine hydrochloride IV over 60 minutes on days 1-2. Treatment repeats every 4
weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

- Arm E: Patients receive consolidation therapy comprising rituximab IV on day 1.
Courses repeat every 8 weeks for 2 years in the absence of disease progression or
unacceptable toxicity.

- Arm B: Patients receive induction therapy comprising bortezomib IV or subcutaneously
(SC) on days 1, 4, 8, and 11 and rituximab and bendamustine hydrochloride as patients
in arm A. Treatment repeats every 4 weeks for 6 courses in the absence of disease
progression or unacceptable toxicity.

- Arm F: Patients receive consolidation therapy comprising rituximab IV on day 1.
Courses repeat every 8 weeks for 2 years in the absence of disease progression or
unacceptable toxicity.

- Arm C: Patients receive induction therapy comprising rituximab and bendamustine
hydrochloride as patients in arm A. Treatment repeats every 4 weeks for 6 courses in
the absence of disease progression or unacceptable toxicity.

- Arm G: Patients receive consolidation therapy comprising lenalidomide orally (PO)
daily on days 1-21 every 4 weeks and rituximab IV every 8 weeks for 2 years in the
absence of disease progression or unacceptable toxicity.

- Arm D: Patients receive bortezomib, rituximab, and bendamustine hydrochloride as
patients in arm B. Treatment repeats every 4 weeks for 6 courses in the absence of
disease progression or unacceptable toxicity.

- Arm H: Patients receive consolidation therapy comprising lenalidomide PO daily on
days 1-21 every 4 weeks and rituximab IV every 8 weeks for 2 years in the absence
of disease progression or unacceptable toxicity.

Patients may undergo blood and bone marrow sample collection at baseline and during
treatment for correlative studies.

Patients complete the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym), the
FACT/GOG-Neurotoxicity scale (FACT/GOG-Ntx), FACT-Fatigue, and FACT-General questionnaires
at baseline and periodically during study and follow up.

After completion of study treatment, patients are followed up every 3 months for 2 years,
every 6 months for 3 years, and then annually for 10 years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed untreated mantle cell lymphoma (MCL), with documented cyclin
D1 by immunohistochemical stains and/or t(11;14) by cytogenetics or fluorescence in
situ hybridization (FISH)

- Patients must have at least one objective measurable disease parameter

- Abnormal PET scans will not constitute evaluable disease, unless verified by CT
scan or other appropriate imaging

- Measurable disease in the liver is required if the liver is the only site of
lymphoma

- Patient must have no CNS involvement

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- ANC ≥ 1,500/mcL (1.5 x 10^9/L)*

- Platelets ≥ 100,000/mcL (100 x 10^9/L)* NOTE: *Unless due to marrow involvement.

- AST/ALT ≤ 2 times upper limit of normal (ULN)

- Bilirubin ≤ 2 times ULN

- Calculated creatinine clearance by Cockroft-Gault formula ≥ 30 mL/min

- Women (sexually mature female) must not be pregnant or breast-feeding

- Negative pregnancy test

- Women of childbearing potential and sexually active males use an accepted and
effective method of contraception

- Men must agree to use a latex condom during sexual contact with a female of
child-bearing potential, even if they have had a successful vasectomy

- All patients must be counseled at a minimum of every 28 days about pregnancy
precautions and risks of fetal exposure

- No evidence of prior malignancy except adequately treated non-melanoma skin cancer,
in situ cervical carcinoma, or any surgically or radiation-cured malignancy
continuously disease free for ≥ 5 years so as not to interfere with interpretation of
radiographic response

- Patient agrees that if randomized to Arms C or D, and proceed onto Arms G or H, they
must register into the mandatory RevAssist® program, and be willing and able to
comply with the requirements of RevAssist®

- Patients must have no medical contra-indications to, and be willing to take,
deep vein thrombosis (DVT) prophylaxis as all patients registering to the
lenalidomide/rituximab Arms G and H will be required to have DVT prophylaxis

- Patients randomized to Arms G or H who have a history of a thrombotic
vascular event will be required to have therapeutic doses of low-molecular
weight heparin or warfarin to maintain an INR between 2.0 - 3.0

- Patients on Arms G and H without a history of a thromboembolic event are
required to take a daily aspirin (81 mg or 325 mg) for DVT prophylaxis

- Patients who are unable to tolerate aspirin should receive low
molecular weight heparin therapy or warfarin treatment

- Women must agree to abstain from donating blood during study participation and
for at least 28 days after discontinuation from protocol treatment

- Males must agree to abstain from donating blood, semen, or sperm during study
participation and for at least 28 days after discontinuation from protocol
treatment

- HIV-positive patients are not excluded but, to enroll, must meet all of the below
criteria:

- HIV is sensitive to antiretroviral therapy

- Must be willing to take effective antiretroviral therapy, if indicated

- No history of CD4 prior to or at the time of lymphoma diagnosis < 300 cells/mm³

- No history of AIDS-defining conditions

- If on antiretroviral therapy, must not be taking zidovudine or stavudine

- Must be willing to take prophylaxis for Pneumocystis jiroveci pneumonia (PCP)
during therapy and until at least 2 months following the completion of therapy
or until the CD4 cells recover to over 250 cells/mm³, whichever occurs later

- Patients must not have grade 2 or greater peripheral neuropathy

- Patients must not have NYHA Class III or IV heart failure, uncontrolled angina,
severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of
acute ischemia

- Patients must not have hypersensitivity to bortezomib, boron, or mannitol

- Patients must not have a serious medical or psychiatric illness likely to interfere
with study participation

PRIOR CONCURRENT THERAPY:

- No prior therapy for MCL, except < 1 week of steroid therapy for symptom control

- HIV-positive patients are not excluded, but to enroll, must meet all of the below
criteria:

- Must be willing to take effective antiretroviral therapy if indicated

- If on antiretroviral therapy, must not be taking zidovudine or stavudine

- Patients must not be participating in any other clinical trial or taking any other
experimental medications within 14 days prior to registration

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

2-year PFS rate of patients treated with RBV to an induction regimen of RB compared to RB alone

Safety Issue:

No

Principal Investigator

Mitchell R. Smith, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fox Chase Cancer Center

Authority:

Unspecified

Study ID:

CDR0000707057

NCT ID:

NCT01415752

Start Date:

May 2012

Completion Date:

Related Keywords:

  • Lymphoma
  • Neurotoxicity
  • Therapy-related Toxicity
  • neurotoxicity
  • therapy-related toxicity
  • contiguous stage II mantle cell lymphoma
  • noncontiguous stage II mantle cell lymphoma
  • stage I mantle cell lymphoma
  • stage III mantle cell lymphoma
  • stage IV mantle cell lymphoma
  • Lymphoma
  • Neurotoxicity Syndromes
  • Lymphoma, Mantle-Cell

Name

Location

Mayo Clinic Cancer Center Rochester, Minnesota  55905
Barbara Ann Karmanos Cancer Institute Detroit, Michigan  48201
Cleveland Clinic Cancer Center Cleveland, Ohio  44195
Hurley Medical Center Flint, Michigan  48503
CCOP - Christiana Care Health Services Wilmington, Delaware  19899
CCOP - Metro-Minnesota Saint Louis Park, Minnesota  55416
Aurora Presbyterian Hospital Aurora, Colorado  80012
Boulder Community Hospital Boulder, Colorado  80301-9019
Penrose Cancer Center at Penrose Hospital Colorado Springs, Colorado  80933
CCOP - Colorado Cancer Research Program Denver, Colorado  80224-2522
Porter Adventist Hospital Denver, Colorado  80210
Presbyterian - St. Luke's Medical Center Denver, Colorado  80218
St. Joseph Hospital Denver, Colorado  80218
Rose Medical Center Denver, Colorado  80220
Swedish Medical Center Englewood, Colorado  80110
Sky Ridge Medical Center Lone Tree, Colorado  80124
Hope Cancer Care Center at Longmont United Hospital Longmont, Colorado  80502
St. Mary - Corwin Regional Medical Center Pueblo, Colorado  81004
Cedar Rapids Oncology Associates Cedar Rapids, Iowa  52403
Mercy Medical Center - Sioux City Sioux City, Iowa  51104
Siouxland Hematology-Oncology Associates, LLP Sioux City, Iowa  51101
St. Luke's Regional Medical Center Sioux City, Iowa  51104
CCOP - Michigan Cancer Research Consortium Ann Arbor, Michigan  48106
Saint Joseph Mercy Cancer Center Ann Arbor, Michigan  48106-0995
Oakwood Cancer Center at Oakwood Hospital and Medical Center Dearborn, Michigan  48123-2500
Genesys Hurley Cancer Institute Flint, Michigan  48503
Van Elslander Cancer Center at St. John Hospital and Medical Center Grosse Pointe Woods, Michigan  48236
Bronson Methodist Hospital Kalamazoo, Michigan  49007
West Michigan Cancer Center Kalamazoo, Michigan  49007-3731
Borgess Medical Center Kalamazooaa, Michigan  49001
Sparrow Regional Cancer Center Lansing, Michigan  48912-1811
St. John Macomb Hospital Warren, Michigan  48093
MeritCare Bemidji Bemidji, Minnesota  56601
Fairview Ridges Hospital Burnsville, Minnesota  55337
Mercy and Unity Cancer Center at Mercy Hospital Coon Rapids, Minnesota  55433
Fairview Southdale Hospital Edina, Minnesota  55435
Mercy and Unity Cancer Center at Unity Hospital Fridley, Minnesota  55432
Hutchinson Area Health Care Hutchinson, Minnesota  55350
HealthEast Cancer Care at St. John's Hospital Maplewood, Minnesota  55109
Hennepin County Medical Center - Minneapolis Minneapolis, Minnesota  55415
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital Minneapolis, Minnesota  55407
St. Francis Cancer Center at St. Francis Medical Center Shakopee, Minnesota  55379
Park Nicollet Cancer Center St. Louis Park, Minnesota  55416
Regions Hospital Cancer Care Center St. Paul, Minnesota  55101
United Hospital St. Paul, Minnesota  55102
Ridgeview Medical Center Waconia, Minnesota  55387
MeritCare Broadway Fargo, North Dakota  58122
CCOP - MeritCare Hospital Fargo, North Dakota  58122
Case Comprehensive Cancer Center Cleveland, Ohio  44106-5065
MetroHealth Cancer Care Center at MetroHealth Medical Center Cleveland, Ohio  44109
Medical College of Wisconsin Cancer Center Milwaukee, Wisconsin  53226
CCOP - Cancer Research for the Ozarks Springfield, Missouri  65807
CCOP - Montana Cancer Consortium Billings, Montana  59101
CCOP - Dayton Kettering, Ohio  45429
Ellis Fischel Cancer Center at University of Missouri - Columbia Columbia, Missouri  65203
Cancer Research Center of Hawaii Honolulu, Hawaii  96813
Cleveland Clinic Taussig Cancer Center Cleveland, Ohio  44195
CCOP - St. Louis-Cape Girardeau Saint Louis, Missouri  63141
Hulston Cancer Center at Cox Medical Center South Springfield, Missouri  65807
St. John's Regional Health Center Springfield, Missouri  65804
Waukesha Memorial Hospital Regional Cancer Center Waukesha, Wisconsin  53188
Mary Babb Randolph Cancer Center at West Virginia University Hospitals Morgantown, West Virginia  26506
St. Vincent Hospital Regional Cancer Center Green Bay, Wisconsin  54307-3508
James P. Wilmot Cancer Center at University of Rochester Medical Center Rochester, New York  14642
Green Bay Oncology, Limited - Escanaba Escanaba, Michigan  49431
Dickinson County Healthcare System Iron Mountain, Michigan  49801
CCOP - Hematology-Oncology Associates of Central New York East Syracuse, New York  13057
St. Mary's Hospital Medical Center - Green Bay Green Bay, Wisconsin  54303
Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center Green Bay, Wisconsin  54301-3526
Green Bay Oncology, Limited at St. Mary's Hospital Green Bay, Wisconsin  54303
Bay Area Cancer Care Center at Bay Area Medical Center Marinette, Wisconsin  54143
Green Bay Oncology, Limited - Oconto Falls Oconto Falls, Wisconsin  54154
Green Bay Oncology, Limited - Sturgeon Bay Sturgeon Bay, Wisconsin  54235
Parma Community General Hospital Parma, Ohio  44129
North Colorado Medical Center Greeley, Colorado  80631
McKee Medical Center Loveland, Colorado  80539
Baptist Cancer Institute - Jacksonville Jacksonville, Florida  32207
Good Samaritan Regional Health Center Mt. Vernon, Illinois  62864
David C. Pratt Cancer Center at St. John's Mercy St. Louis, Missouri  63141
Hematology-Oncology Centers of the Northern Rockies - Billings Billings, Montana  59101
St. Peter's Hospital Helena, Montana  59601
Kalispell Regional Medical Center Kalispell, Montana  59901
Glacier Oncology, PLLC Kalispell, Montana  59901
Montana Cancer Center at St. Patrick Hospital and Health Sciences Center Missoula, Montana  59802
Montana Cancer Specialists at Montana Cancer Center Missoula, Montana  59802
Wayne Memorial Hospital, Incorporated Goldsboro, North Carolina  27534
New York Weill Cornell Cancer Center at Cornell University New York, New York  10021
Lombardi Comprehensive Cancer Center at Georgetown University Medical Center Washington, District of Columbia  20007
Swedish-American Regional Cancer Center Rockford, Illinois  61104-2315
CancerCare of Maine at Eastern Maine Medical Center Bangor, Maine  04401
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis St. Louis, Missouri  63110
Gundersen Lutheran Center for Cancer and Blood La Crosse, Wisconsin  54601
University of Virginia Cancer Center Charlottesville, Virginia  22908
Robert H. Lurie Comprehensive Cancer Center at Northwestern University Chicago, Illinois  60611
Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center Hartford, Connecticut  06105
Cleveland Clinic Cancer Center at Fairview Hospital Cleveland, Ohio  44111
Hillcrest Cancer Center at Hillcrest Hospital Mayfield Heights, Ohio  44124
Fox Chase Cancer Center - Philadelphia Philadelphia, Pennsylvania  19111-2497
Hematology Oncology Associates - Skokie Skokie, Illinois  60076
Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center Boise, Idaho  83706
Hematology and Oncology Associates Chicago, Illinois  60611
North Shore Oncology and Hematology Associates, Limited - Libertyville Libertyville, Illinois  60048
St. Francis Hospital and Health Centers - Beech Grove Campus Beech Grove, Indiana  46107
Mercy Regional Cancer Center at Mercy Medical Center Cedar Rapids, Iowa  52403
Saint Francis Medical Center Cape Girardeau, Missouri  63701
Cancer Institute of New Jersey at Cooper - Voorhees Voorhees, New Jersey  08043
Charles R. Wood Cancer Center at Glens Falls Hospital Glens Falls, New York  12801
Iredell Memorial Hospital Statesville, North Carolina  28677
Samaritan North Cancer Care Center Dayton, Ohio  45415
Grandview Hospital Dayton, Ohio  45405
David L. Rike Cancer Center at Miami Valley Hospital Dayton, Ohio  45409
Good Samaritan Hospital Dayton, Ohio  45406
Blanchard Valley Medical Associates Findlay, Ohio  45840
Charles F. Kettering Memorial Hospital Kettering, Ohio  45429
Middletown Regional Hospital Middletown, Ohio  45044
North Coast Cancer Care, Incorporated Sandusky, Ohio  44870
UVMC Cancer Care Center at Upper Valley Medical Center Troy, Ohio  45373-1300
Cleveland Clinic - Wooster Wooster, Ohio  44691
Ruth G. McMillan Cancer Center at Greene Memorial Hospital Xenia, Ohio  45385
Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center Kingsport, Tennessee  37662
Holy Family Memorial Medical Center Cancer Care Center Manitowoc, Wisconsin  54221-1450
St. Anthony Central Hospital Denver, Colorado  80204-1335
Exempla Lutheran Medical Center Wheat Ridge, Colorado  80033
Pottstown Memorial Regional Cancer Center Pottstown, Pennsylvania  19464
Missouri Baptist Cancer Center St. Louis, Missouri  63131
Stanford Cancer Center Stanford, California  94305-5824
Tunnell Cancer Center at Beebe Medical Center Lewes, Delaware  19958
Kellogg Cancer Care Center Highland Park, Illinois  60035
Cancer Care and Hematology Specialists of Chicagoland - Niles Niles, Illinois  60714
Reid Hospital & Health Care Services Richmond, Indiana  47374
McFarland Clinic, PC Ames, Iowa  50010
Foote Memorial Hospital Jackson, Michigan  49201
St. Mary Mercy Hospital Livonia, Michigan  48154
St. Joseph Mercy Oakland Pontiac, Michigan  48341-2985
Mercy Regional Cancer Center at Mercy Hospital Port Huron, Michigan  48060
Seton Cancer Institute at Saint Mary's - Saginaw Saginaw, Michigan  48601
Willmar Cancer Center at Rice Memorial Hospital Willmar, Minnesota  56201
Billings Clinic - Downtown Billings, Montana  59107-7000
Bozeman Deaconess Cancer Center Bozeman, Montana  59715
St. James Healthcare Cancer Care Butte, Montana  59701
Great Falls Clinic - Main Facility Great Falls, Montana  59405
Sletten Cancer Institute at Benefis Healthcare Great Falls, Montana  59405
Kalispell Medical Oncology at KRMC Kalispell, Montana  59901
Summa Center for Cancer Care at Akron City Hospital Akron, Ohio  44309-2090
Barberton Citizens Hospital Barberton, Ohio  44203
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center Columbus, Ohio  43210-1240
Wayne Hospital Greenville, Ohio  45331
Southwest Virginia Regional Cancer Center at Wellmonth Health Norton, Virginia  24273
Rocky Mountain Oncology Casper, Wyoming  82609
Genesys Regional Medical Center Grand Blanc, Michigan  48439-8066
Queen's Cancer Institute at Queen's Medical Center Honolulu, Hawaii  96813
Tucker Center for Cancer Care at Orange Regional Medical Center Middletown, New York  10940-4199
Pardee Memorial Hospital Hendersonville, North Carolina  28791
Regional Cancer Center at Oconomowoc Memorial Hospital Oconomowoc, Wisconsin  53066
Harold Alfond Center for Cancer Care Augusta, Maine  04330
Union Hospital of Cecil County Elkton MD, Maryland  21921
Kinston Medical Specialists Kinston, North Carolina  28501
Phelps County Regional Medical Center Rolla, Missouri  65401
University of Wisconcin Cancer Center at Aspirus Wausau Hospital Wausau, Wisconsin  54401
St. Vincent Healthcare Cancer Care Services Billings, Montana  59101
Midwest Hematology Oncology Group, Incorporated Saint Louis, Missouri  63109
Kapiolani Medical Center at Pali Momi Aiea, Hawaii  96701
Kapiolani Medical Center for Women and Children Honolulu, Hawaii  96826
Straub Clinic and Hospital, Incorporated Honolulu, Hawaii  96813
OnCare Hawaii, Incorporated - Kuakini Honolulu, Hawaii  96817
OnCare Hawaii, Incorporated - Lusitana Honolulu, Hawaii  96813
Provena St. Mary's Regional Cancer Center - Kankakee Kankakee, Illinois  60901
Minnesota Oncology - Maplewood Maplewood, Minnesota  55109
Humphrey Cancer Center at North Memorial Outpatient Center Robbinsdale, Minnesota  55422-2900
Lakeview Hospital Stillwater, Minnesota  55082
Minnesota Oncology - Woodbury Woodbury, Minnesota  55125
Ravenel Oncology Center at Memorial Hospital of Martinsville and Henry County Martinsville, Virginia  24115
Clarian Arnett Cancer Care Lafayette, Indiana  47904
Langlade Memorial Hospital Antigo, Wisconsin  54409
Castle Medical Center Kailua, Hawaii  96734
Kauai Medical Clinic Lihue, Hawaii  96766
Southeast Cancer Center Cape Girardeau, Missouri  63703
Goldschmidt Cancer Center Jefferson City, Missouri  65109
Cleveland Clinic Beachwood Family Health and Surgery Center Beachwood, Ohio  44122
Cleveland Clinic Foundation - Strongsville Strongsville, Ohio  44136
Littleton Adventist Hospital Littleton, Colorado  80122
Parker Adventist Hospital Parker, Colorado  80138
New Ulm Medical Center New Ulm, Minnesota  56073
Roger Maris Cancer Center at MeritCare Hospital Fargo, North Dakota  58122
St. Nicholas Hospital Sheboygan, Wisconsin  53081
Mercy Clinic Cancer and Hematology - Rolla Rolla, Missouri  65401
D.N. Greenwald Center Mukwonago, Wisconsin  53149
Idaho Urologic Institute, PA Meridian, Idaho  83642
Oncare Hawaii, Incorporated - Pali Momi Aiea, Hawaii  96701
Wellmont-Bristol Regional Medical Center Bristol, Tennessee  37620