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)
60 Years
N/A
Both
Lymphoma, Neurotoxicity, Therapy-related Toxicity
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 |
