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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 CenterRochester, Minnesota  55905
Barbara Ann Karmanos Cancer InstituteDetroit, Michigan  48201
Cleveland Clinic Cancer CenterCleveland, Ohio  44195
Hurley Medical CenterFlint, Michigan  48503
CCOP - Christiana Care Health ServicesWilmington, Delaware  19899
CCOP - Metro-MinnesotaSaint Louis Park, Minnesota  55416
Aurora Presbyterian HospitalAurora, Colorado  80012
Boulder Community HospitalBoulder, Colorado  80301-9019
Penrose Cancer Center at Penrose HospitalColorado Springs, Colorado  80933
CCOP - Colorado Cancer Research ProgramDenver, Colorado  80224-2522
Porter Adventist HospitalDenver, Colorado  80210
Presbyterian - St. Luke's Medical CenterDenver, Colorado  80218
St. Joseph HospitalDenver, Colorado  80218
Rose Medical CenterDenver, Colorado  80220
Swedish Medical CenterEnglewood, Colorado  80110
Sky Ridge Medical CenterLone Tree, Colorado  80124
Hope Cancer Care Center at Longmont United HospitalLongmont, Colorado  80502
St. Mary - Corwin Regional Medical CenterPueblo, Colorado  81004
Cedar Rapids Oncology AssociatesCedar Rapids, Iowa  52403
Mercy Medical Center - Sioux CitySioux City, Iowa  51104
Siouxland Hematology-Oncology Associates, LLPSioux City, Iowa  51101
St. Luke's Regional Medical CenterSioux City, Iowa  51104
CCOP - Michigan Cancer Research ConsortiumAnn Arbor, Michigan  48106
Saint Joseph Mercy Cancer CenterAnn Arbor, Michigan  48106-0995
Oakwood Cancer Center at Oakwood Hospital and Medical CenterDearborn, Michigan  48123-2500
Genesys Hurley Cancer InstituteFlint, Michigan  48503
Van Elslander Cancer Center at St. John Hospital and Medical CenterGrosse Pointe Woods, Michigan  48236
Bronson Methodist HospitalKalamazoo, Michigan  49007
West Michigan Cancer CenterKalamazoo, Michigan  49007-3731
Borgess Medical CenterKalamazooaa, Michigan  49001
Sparrow Regional Cancer CenterLansing, Michigan  48912-1811
St. John Macomb HospitalWarren, Michigan  48093
MeritCare BemidjiBemidji, Minnesota  56601
Fairview Ridges HospitalBurnsville, Minnesota  55337
Mercy and Unity Cancer Center at Mercy HospitalCoon Rapids, Minnesota  55433
Fairview Southdale HospitalEdina, Minnesota  55435
Mercy and Unity Cancer Center at Unity HospitalFridley, Minnesota  55432
Hutchinson Area Health CareHutchinson, Minnesota  55350
HealthEast Cancer Care at St. John's HospitalMaplewood, Minnesota  55109
Hennepin County Medical Center - MinneapolisMinneapolis, Minnesota  55415
Virginia Piper Cancer Institute at Abbott - Northwestern HospitalMinneapolis, Minnesota  55407
St. Francis Cancer Center at St. Francis Medical CenterShakopee, Minnesota  55379
Park Nicollet Cancer CenterSt. Louis Park, Minnesota  55416
Regions Hospital Cancer Care CenterSt. Paul, Minnesota  55101
United HospitalSt. Paul, Minnesota  55102
Ridgeview Medical CenterWaconia, Minnesota  55387
MeritCare BroadwayFargo, North Dakota  58122
CCOP - MeritCare HospitalFargo, North Dakota  58122
Case Comprehensive Cancer CenterCleveland, Ohio  44106-5065
MetroHealth Cancer Care Center at MetroHealth Medical CenterCleveland, Ohio  44109
Medical College of Wisconsin Cancer CenterMilwaukee, Wisconsin  53226
CCOP - Cancer Research for the OzarksSpringfield, Missouri  65807
CCOP - Montana Cancer ConsortiumBillings, Montana  59101
CCOP - DaytonKettering, Ohio  45429
Ellis Fischel Cancer Center at University of Missouri - ColumbiaColumbia, Missouri  65203
Cancer Research Center of HawaiiHonolulu, Hawaii  96813
Cleveland Clinic Taussig Cancer CenterCleveland, Ohio  44195
CCOP - St. Louis-Cape GirardeauSaint Louis, Missouri  63141
Hulston Cancer Center at Cox Medical Center SouthSpringfield, Missouri  65807
St. John's Regional Health CenterSpringfield, Missouri  65804
Waukesha Memorial Hospital Regional Cancer CenterWaukesha, Wisconsin  53188
Mary Babb Randolph Cancer Center at West Virginia University HospitalsMorgantown, West Virginia  26506
St. Vincent Hospital Regional Cancer CenterGreen Bay, Wisconsin  54307-3508
James P. Wilmot Cancer Center at University of Rochester Medical CenterRochester, New York  14642
Green Bay Oncology, Limited - EscanabaEscanaba, Michigan  49431
Dickinson County Healthcare SystemIron Mountain, Michigan  49801
CCOP - Hematology-Oncology Associates of Central New YorkEast Syracuse, New York  13057
St. Mary's Hospital Medical Center - Green BayGreen Bay, Wisconsin  54303
Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer CenterGreen Bay, Wisconsin  54301-3526
Green Bay Oncology, Limited at St. Mary's HospitalGreen Bay, Wisconsin  54303
Bay Area Cancer Care Center at Bay Area Medical CenterMarinette, Wisconsin  54143
Green Bay Oncology, Limited - Oconto FallsOconto Falls, Wisconsin  54154
Green Bay Oncology, Limited - Sturgeon BaySturgeon Bay, Wisconsin  54235
Parma Community General HospitalParma, Ohio  44129
North Colorado Medical CenterGreeley, Colorado  80631
McKee Medical CenterLoveland, Colorado  80539
Baptist Cancer Institute - JacksonvilleJacksonville, Florida  32207
Good Samaritan Regional Health CenterMt. Vernon, Illinois  62864
David C. Pratt Cancer Center at St. John's MercySt. Louis, Missouri  63141
Hematology-Oncology Centers of the Northern Rockies - BillingsBillings, Montana  59101
St. Peter's HospitalHelena, Montana  59601
Kalispell Regional Medical CenterKalispell, Montana  59901
Glacier Oncology, PLLCKalispell, Montana  59901
Montana Cancer Center at St. Patrick Hospital and Health Sciences CenterMissoula, Montana  59802
Montana Cancer Specialists at Montana Cancer CenterMissoula, Montana  59802
Wayne Memorial Hospital, IncorporatedGoldsboro, North Carolina  27534
New York Weill Cornell Cancer Center at Cornell UniversityNew York, New York  10021
Lombardi Comprehensive Cancer Center at Georgetown University Medical CenterWashington, District of Columbia  20007
Swedish-American Regional Cancer CenterRockford, Illinois  61104-2315
CancerCare of Maine at Eastern Maine Medical CenterBangor, Maine  04401
Siteman Cancer Center at Barnes-Jewish Hospital - Saint LouisSt. Louis, Missouri  63110
Gundersen Lutheran Center for Cancer and BloodLa Crosse, Wisconsin  54601
University of Virginia Cancer CenterCharlottesville, Virginia  22908
Robert H. Lurie Comprehensive Cancer Center at Northwestern UniversityChicago, Illinois  60611
Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical CenterHartford, Connecticut  06105
Cleveland Clinic Cancer Center at Fairview HospitalCleveland, Ohio  44111
Hillcrest Cancer Center at Hillcrest HospitalMayfield Heights, Ohio  44124
Fox Chase Cancer Center - PhiladelphiaPhiladelphia, Pennsylvania  19111-2497
Hematology Oncology Associates - SkokieSkokie, Illinois  60076
Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical CenterBoise, Idaho  83706
Hematology and Oncology AssociatesChicago, Illinois  60611
North Shore Oncology and Hematology Associates, Limited - LibertyvilleLibertyville, Illinois  60048
St. Francis Hospital and Health Centers - Beech Grove CampusBeech Grove, Indiana  46107
Mercy Regional Cancer Center at Mercy Medical CenterCedar Rapids, Iowa  52403
Saint Francis Medical CenterCape Girardeau, Missouri  63701
Cancer Institute of New Jersey at Cooper - VoorheesVoorhees, New Jersey  08043
Charles R. Wood Cancer Center at Glens Falls HospitalGlens Falls, New York  12801
Iredell Memorial HospitalStatesville, North Carolina  28677
Samaritan North Cancer Care CenterDayton, Ohio  45415
Grandview HospitalDayton, Ohio  45405
David L. Rike Cancer Center at Miami Valley HospitalDayton, Ohio  45409
Good Samaritan HospitalDayton, Ohio  45406
Blanchard Valley Medical AssociatesFindlay, Ohio  45840
Charles F. Kettering Memorial HospitalKettering, Ohio  45429
Middletown Regional HospitalMiddletown, Ohio  45044
North Coast Cancer Care, IncorporatedSandusky, Ohio  44870
UVMC Cancer Care Center at Upper Valley Medical CenterTroy, Ohio  45373-1300
Cleveland Clinic - WoosterWooster, Ohio  44691
Ruth G. McMillan Cancer Center at Greene Memorial HospitalXenia, Ohio  45385
Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical CenterKingsport, Tennessee  37662
Holy Family Memorial Medical Center Cancer Care CenterManitowoc, Wisconsin  54221-1450
St. Anthony Central HospitalDenver, Colorado  80204-1335
Exempla Lutheran Medical CenterWheat Ridge, Colorado  80033
Pottstown Memorial Regional Cancer CenterPottstown, Pennsylvania  19464
Missouri Baptist Cancer CenterSt. Louis, Missouri  63131
Stanford Cancer CenterStanford, California  94305-5824
Tunnell Cancer Center at Beebe Medical CenterLewes, Delaware  19958
Kellogg Cancer Care CenterHighland Park, Illinois  60035
Cancer Care and Hematology Specialists of Chicagoland - NilesNiles, Illinois  60714
Reid Hospital & Health Care ServicesRichmond, Indiana  47374
McFarland Clinic, PCAmes, Iowa  50010
Foote Memorial HospitalJackson, Michigan  49201
St. Mary Mercy HospitalLivonia, Michigan  48154
St. Joseph Mercy OaklandPontiac, Michigan  48341-2985
Mercy Regional Cancer Center at Mercy HospitalPort Huron, Michigan  48060
Seton Cancer Institute at Saint Mary's - SaginawSaginaw, Michigan  48601
Willmar Cancer Center at Rice Memorial HospitalWillmar, Minnesota  56201
Billings Clinic - DowntownBillings, Montana  59107-7000
Bozeman Deaconess Cancer CenterBozeman, Montana  59715
St. James Healthcare Cancer CareButte, Montana  59701
Great Falls Clinic - Main FacilityGreat Falls, Montana  59405
Sletten Cancer Institute at Benefis HealthcareGreat Falls, Montana  59405
Kalispell Medical Oncology at KRMCKalispell, Montana  59901
Summa Center for Cancer Care at Akron City HospitalAkron, Ohio  44309-2090
Barberton Citizens HospitalBarberton, Ohio  44203
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer CenterColumbus, Ohio  43210-1240
Wayne HospitalGreenville, Ohio  45331
Southwest Virginia Regional Cancer Center at Wellmonth HealthNorton, Virginia  24273
Rocky Mountain OncologyCasper, Wyoming  82609
Genesys Regional Medical CenterGrand Blanc, Michigan  48439-8066
Queen's Cancer Institute at Queen's Medical CenterHonolulu, Hawaii  96813
Tucker Center for Cancer Care at Orange Regional Medical CenterMiddletown, New York  10940-4199
Pardee Memorial HospitalHendersonville, North Carolina  28791
Regional Cancer Center at Oconomowoc Memorial HospitalOconomowoc, Wisconsin  53066
Harold Alfond Center for Cancer CareAugusta, Maine  04330
Union Hospital of Cecil CountyElkton MD, Maryland  21921
Kinston Medical SpecialistsKinston, North Carolina  28501
Phelps County Regional Medical CenterRolla, Missouri  65401
University of Wisconcin Cancer Center at Aspirus Wausau HospitalWausau, Wisconsin  54401
St. Vincent Healthcare Cancer Care ServicesBillings, Montana  59101
Midwest Hematology Oncology Group, IncorporatedSaint Louis, Missouri  63109
Kapiolani Medical Center at Pali MomiAiea, Hawaii  96701
Kapiolani Medical Center for Women and ChildrenHonolulu, Hawaii  96826
Straub Clinic and Hospital, IncorporatedHonolulu, Hawaii  96813
OnCare Hawaii, Incorporated - KuakiniHonolulu, Hawaii  96817
OnCare Hawaii, Incorporated - LusitanaHonolulu, Hawaii  96813
Provena St. Mary's Regional Cancer Center - KankakeeKankakee, Illinois  60901
Minnesota Oncology - MaplewoodMaplewood, Minnesota  55109
Humphrey Cancer Center at North Memorial Outpatient CenterRobbinsdale, Minnesota  55422-2900
Lakeview HospitalStillwater, Minnesota  55082
Minnesota Oncology - WoodburyWoodbury, Minnesota  55125
Ravenel Oncology Center at Memorial Hospital of Martinsville and Henry CountyMartinsville, Virginia  24115
Clarian Arnett Cancer CareLafayette, Indiana  47904
Langlade Memorial HospitalAntigo, Wisconsin  54409
Castle Medical CenterKailua, Hawaii  96734
Kauai Medical ClinicLihue, Hawaii  96766
Southeast Cancer CenterCape Girardeau, Missouri  63703
Goldschmidt Cancer CenterJefferson City, Missouri  65109
Cleveland Clinic Beachwood Family Health and Surgery CenterBeachwood, Ohio  44122
Cleveland Clinic Foundation - StrongsvilleStrongsville, Ohio  44136
Littleton Adventist HospitalLittleton, Colorado  80122
Parker Adventist HospitalParker, Colorado  80138
New Ulm Medical CenterNew Ulm, Minnesota  56073
Roger Maris Cancer Center at MeritCare HospitalFargo, North Dakota  58122
St. Nicholas HospitalSheboygan, Wisconsin  53081
Mercy Clinic Cancer and Hematology - RollaRolla, Missouri  65401
D.N. Greenwald CenterMukwonago, Wisconsin  53149
Idaho Urologic Institute, PAMeridian, Idaho  83642
Oncare Hawaii, Incorporated - Pali MomiAiea, Hawaii  96701
Wellmont-Bristol Regional Medical CenterBristol, Tennessee  37620