Vorinostat, Rituximab, and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Diffuse Large B-Cell Lymphoma
- Conditions
- Ann Arbor Stage III Non-Hodgkin LymphomaAnn Arbor Stage II Non-Hodgkin LymphomaAnn Arbor Stage IV Non-Hodgkin Lymphoma
- Interventions
- Other: Laboratory Biomarker Analysis
- Registration Number
- NCT00972478
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
This phase I/II trial is studying the side effects and best dose of vorinostat when given together with rituximab and combination chemotherapy and to see how well it works in treating patients with newly diagnosed stage II, stage III, or stage IV diffuse large B-cell lymphoma. Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Monoclonal antibodies, such as rituximab, can block cancer cell growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cell-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving vorinostat together with rituximab and combination chemotherapy may kill more cancer cells.
- Detailed Description
PRIMARY OBJECTIVES:
I. To find a safe dose of vorinostat to be used in combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone) (vorinostat-R-CHOP). (Phase I) II. To estimate the 2-year progression-free survival (PFS) rate in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) treated with vorinostat and R-CHOP therapy (vorinostat-R-CHOP). (Phase II) III. To estimate the response rate (complete and partial) and 2-year overall survival rate. (Phase II) IV. To evaluate the toxicity of vorinostat-R-CHOP in patients with newly diagnosed DLBCL. (Phase II) V. To assess whether pre-treatment acetylation status of histones, expression of major histocompatibility complex (MHC) class II genes, and/or percentage of cluster of differentiation (CD)8+ tumor infiltrating lymphocytes correlate with progression-free survival. (Phase II) VI. To explore whether treatment with vorinostat-R-CHOP increases histone acetylation, alters expression of MHC class II proteins, or alters percentage of T-cell subsets (CD8+, CD4+, forkhead box P3 \[FOXP3\]+) or infiltrating macrophages. (Phase II) VII. To explore whether histone acetylation status of tumor tissues correlates with MHC class II expression of peripheral blood B cells and lymphocyte subsets. (Phase II) VIII. To explore whether the change in systemic levels of immune cytokines with vorinostat-R-CHOP correlates with lymphoma symptoms, response, progression-free or overall survival. (Phase II)
OUTLINE: This is a phase I, dose escalation study of vorinostat followed by a phase II study.
Patients receive vorinostat orally (PO) once daily on days 1-5 or 1-9 (according to dose level), rituximab intravenously (IV), cyclophosphamide IV over 30-60 minutes, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 3. Patients also receive prednisone PO once daily on days 3-7. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 6 months for 2 years, and then annually for 3 years.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 83
- Patients must have biopsy proven, newly diagnosed DLBCL with stage II bulky, stage III or stage IV disease, with an International Prognostic Index (IPI) or revised (R)-IPI score greater than 0; a report providing confirmation of CD20 expression must be submitted
- Adequate sections from the original diagnostic specimen must be available for submission for review by the Southwest Oncology Group (SWOG) Lymphoma Pathology Laboratory; an adequate biopsy requires sufficient tissue to establish the architecture and World Health Organization (WHO) histologic subtype with certainty; fine needle aspiration or cytology is not adequate
- Patients must be offered the opportunity to consent to the correlative science studies; patients are encouraged to submit specimens for correlative studies; however, specimen submission is not a requirement for participation in the study
- Patients must have measurable disease; measurable disease must be determined by computed tomography (CT) scan of chest, abdomen and pelvis performed within 28 days prior to registration; positron emission tomography (PET)/CT may be substituted for CT scan only if CT scan is of diagnostic quality and is contrast enhanced
- Patients must have a unilateral bone marrow aspirate and biopsy for staging performed within 42 days prior to registration
- Patients must not have clinical evidence of central nervous system involvement by lymphoma; any laboratory or radiographic tests performed within 42 days prior to registration to assess central nervous system (CNS) involvement must be negative
- Patients must not have received prior chemotherapy, radiation, or antibody therapy for lymphoma; steroid pre-medication for IV contrast allergy is allowed
- Patients must have Zubrod performance status of 0-2
- Patients must have serum lactate dehydrogenase (LDH) measured within 28 days prior to registration
- Absolute neutrophil count (ANC) > 1,000/mcL within 28 days prior to registration, unless due to bone marrow infiltration by lymphoma
- Platelets > 100,000/mcL within 28 days prior to registration, unless due to bone marrow infiltration by lymphoma
- Cardiac ejection fraction ≥ institutional lower limit of normal (ILLN) by multigated acquisition (MUGA) scan or 2-dimensional (2-D) echocardiogram (ECHO) with no significant abnormalities within 42 days prior to registration
- Patients must not have received valproic acid (a histone deacetylase [HDAC] inhibitor) within 28 days prior to registration
- Patients must have no known hypersensitivity to the components of treatment
- Patients must be willing to discontinue taking any medications that are generally accepted to have a risk of causing Torsades de Pointes while on study
- Patients known to be human immunodeficiency virus (HIV) positive are not eligible; existing therapeutic options are effective and study design does not support assessing the efficacy of treatment on those with HIV
- No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years
- Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
- All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
- At the time of patient registration, the treating institution's name and identification (ID) number must be provided to the Data Operations Center in Seattle in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the data base
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (combination chemotherapy) Vincristine Sulfate Patients receive vorinostat PO once daily on days 1-5 or 1-9 (according to dose level), rituximab IV, cyclophosphamide IV over 30-60 minutes, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 3. Patients also receive prednisone PO once daily on days 3-7. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. Treatment (combination chemotherapy) Cyclophosphamide Patients receive vorinostat PO once daily on days 1-5 or 1-9 (according to dose level), rituximab IV, cyclophosphamide IV over 30-60 minutes, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 3. Patients also receive prednisone PO once daily on days 3-7. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. Treatment (combination chemotherapy) Doxorubicin Hydrochloride Patients receive vorinostat PO once daily on days 1-5 or 1-9 (according to dose level), rituximab IV, cyclophosphamide IV over 30-60 minutes, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 3. Patients also receive prednisone PO once daily on days 3-7. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. Treatment (combination chemotherapy) Laboratory Biomarker Analysis Patients receive vorinostat PO once daily on days 1-5 or 1-9 (according to dose level), rituximab IV, cyclophosphamide IV over 30-60 minutes, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 3. Patients also receive prednisone PO once daily on days 3-7. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. Treatment (combination chemotherapy) Prednisone Patients receive vorinostat PO once daily on days 1-5 or 1-9 (according to dose level), rituximab IV, cyclophosphamide IV over 30-60 minutes, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 3. Patients also receive prednisone PO once daily on days 3-7. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. Treatment (combination chemotherapy) Rituximab Patients receive vorinostat PO once daily on days 1-5 or 1-9 (according to dose level), rituximab IV, cyclophosphamide IV over 30-60 minutes, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 3. Patients also receive prednisone PO once daily on days 3-7. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. Treatment (combination chemotherapy) Vorinostat Patients receive vorinostat PO once daily on days 1-5 or 1-9 (according to dose level), rituximab IV, cyclophosphamide IV over 30-60 minutes, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 3. Patients also receive prednisone PO once daily on days 3-7. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Safe Dose of Vorinostat to be Used in Combination With R-CHOP Assessed by CTCAE Version 4.0 (Phase I) 21 days Safe dose of Vorinostat (in combination with R-CHOP) at which 3/10 or fewer patients have doselimiting toxicities (DLT). Toxicities graded according to the NCI Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE 4.0). DLT apply only during cycle 1 and should be drug-related (possible, probable, or definite).
Progression-free Survival (Phase II) Up to 2 years From date of registration to date of first documentation of progressive disease, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact.
- Secondary Outcome Measures
Name Time Method Overall Survival (Phase II) Up to 2 years From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.
Toxicity of Vorinostat-R-CHOP in Patients With Newly Diagnosed DLBCL Up to week 26 Incidence of toxicity as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.
Response Rate (Complete Response [CR]+Partial Response [PR]) (Phase II) Up to week 26 Objective disease status is evaluated according to the 2007 revised Cheson et al. criteria. Complete Response(CR) is a complete disappearance of all disease with the exception of nodes. No new lesions. previously enlarged organs must have regressed and not be palpable. Bone marrow (BM) must be negative if positive at baseline. Normalization of markers. Partial Response (PR) is a 50% decrease in the sum of products of greatest diameters (SPD) for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes.
Trial Locations
- Locations (190)
Kaiser Permanente-Oakland
🇺🇸Oakland, California, United States
Kaiser Permanente-Vallejo
🇺🇸Vallejo, California, United States
Kaiser Permanente-Modesto
🇺🇸Modesto, California, United States
Providence Hospital
🇺🇸Mobile, Alabama, United States
University of Arizona Cancer Center-Orange Grove Campus
🇺🇸Tucson, Arizona, United States
Banner University Medical Center - Tucson
🇺🇸Tucson, Arizona, United States
University of Arizona Cancer Center-North Campus
🇺🇸Tucson, Arizona, United States
Mercy Hospital Fort Smith
🇺🇸Fort Smith, Arkansas, United States
NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
🇺🇸Jonesboro, Arkansas, United States
NEA Baptist Memorial Hospital
🇺🇸Jonesboro, Arkansas, United States
Kaiser Permanente-Deer Valley Medical Center
🇺🇸Antioch, California, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
Kaiser Permanente-Fremont
🇺🇸Fremont, California, United States
Kaiser Permanente-Fresno
🇺🇸Fresno, California, United States
USC / Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Kaiser Permanente-Redwood City
🇺🇸Redwood City, California, United States
Kaiser Permanente-Richmond
🇺🇸Richmond, California, United States
Kaiser Permanente-Roseville
🇺🇸Roseville, California, United States
Kaiser Permanente-South Sacramento
🇺🇸Sacramento, California, United States
Kaiser Permanente Sacramento Medical Center
🇺🇸Sacramento, California, United States
Kaiser Permanente-San Francisco
🇺🇸San Francisco, California, United States
Kaiser Permanente-Santa Teresa-San Jose
🇺🇸San Jose, California, United States
Kaiser Permanente San Leandro
🇺🇸San Leandro, California, United States
Kaiser Permanente-San Rafael
🇺🇸San Rafael, California, United States
Kaiser Permanente Medical Center - Santa Clara
🇺🇸Santa Clara, California, United States
Kaiser Permanente-Santa Rosa
🇺🇸Santa Rosa, California, United States
Kaiser Permanente-South San Francisco
🇺🇸South San Francisco, California, United States
Kaiser Permanente-Stockton
🇺🇸Stockton, California, United States
Kaiser Permanente Medical Center-Vacaville
🇺🇸Vacaville, California, United States
Kaiser Permanente-Walnut Creek
🇺🇸Walnut Creek, California, United States
Poudre Valley Hospital
🇺🇸Fort Collins, Colorado, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Memorial Health University Medical Center
🇺🇸Savannah, Georgia, United States
Pali Momi Medical Center
🇺🇸'Aiea, Hawaii, United States
Queen's Cancer Center - Pearlridge
🇺🇸'Aiea, Hawaii, United States
Hawaii Cancer Care Inc - Waterfront Plaza
🇺🇸Honolulu, Hawaii, United States
Queen's Medical Center
🇺🇸Honolulu, Hawaii, United States
Straub Clinic and Hospital
🇺🇸Honolulu, Hawaii, United States
University of Hawaii Cancer Center
🇺🇸Honolulu, Hawaii, United States
Hawaii Cancer Care Inc-Liliha
🇺🇸Honolulu, Hawaii, United States
Kuakini Medical Center
🇺🇸Honolulu, Hawaii, United States
Queen's Cancer Center - Kuakini
🇺🇸Honolulu, Hawaii, United States
Kaiser Permanente Moanalua Medical Center
🇺🇸Honolulu, Hawaii, United States
Kapiolani Medical Center for Women and Children
🇺🇸Honolulu, Hawaii, United States
Tripler Army Medical Center
🇺🇸Honolulu, Hawaii, United States
Castle Medical Center
🇺🇸Kailua, Hawaii, United States
Wilcox Memorial Hospital and Kauai Medical Clinic
🇺🇸Lihue, Hawaii, United States
Northwestern Medicine Cancer Center Delnor
🇺🇸Geneva, Illinois, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
SSM Health Good Samaritan
🇺🇸Mount Vernon, Illinois, United States
Northwestern Medicine Cancer Center Warrenville
🇺🇸Warrenville, Illinois, United States
Franciscan Saint Francis Health-Beech Grove
🇺🇸Beech Grove, Indiana, United States
Franciscan Health Indianapolis
🇺🇸Indianapolis, Indiana, United States
Reid Health
🇺🇸Richmond, Indiana, United States
Cancer Center of Kansas - Chanute
🇺🇸Chanute, Kansas, United States
Cancer Center of Kansas - Dodge City
🇺🇸Dodge City, Kansas, United States
Cancer Center of Kansas - El Dorado
🇺🇸El Dorado, Kansas, United States
Cancer Center of Kansas - Fort Scott
🇺🇸Fort Scott, Kansas, United States
Saint Rose Ambulatory and Surgery Center
🇺🇸Great Bend, Kansas, United States
HaysMed
🇺🇸Hays, Kansas, United States
Hutchinson Regional Medical Center
🇺🇸Hutchinson, Kansas, United States
Cancer Center of Kansas-Independence
🇺🇸Independence, Kansas, United States
Providence Medical Center
🇺🇸Kansas City, Kansas, United States
University of Kansas Cancer Center
🇺🇸Kansas City, Kansas, United States
Cancer Center of Kansas-Kingman
🇺🇸Kingman, Kansas, United States
Lawrence Memorial Hospital
🇺🇸Lawrence, Kansas, United States
Cancer Center of Kansas-Liberal
🇺🇸Liberal, Kansas, United States
Cancer Center of Kansas - Newton
🇺🇸Newton, Kansas, United States
Menorah Medical Center
🇺🇸Overland Park, Kansas, United States
Saint Luke's South Hospital
🇺🇸Overland Park, Kansas, United States
Cancer Center of Kansas - Parsons
🇺🇸Parsons, Kansas, United States
Mercy Hospital Pittsburg
🇺🇸Pittsburg, Kansas, United States
Kansas City NCI Community Oncology Research Program
🇺🇸Prairie Village, Kansas, United States
Cancer Center of Kansas - Pratt
🇺🇸Pratt, Kansas, United States
Cancer Center of Kansas - Salina
🇺🇸Salina, Kansas, United States
Salina Regional Health Center
🇺🇸Salina, Kansas, United States
University of Kansas Health System Saint Francis Campus
🇺🇸Topeka, Kansas, United States
Cancer Center of Kansas - Wellington
🇺🇸Wellington, Kansas, United States
Associates In Womens Health
🇺🇸Wichita, Kansas, United States
Cancer Center of Kansas-Wichita Medical Arts Tower
🇺🇸Wichita, Kansas, United States
Ascension Via Christi Hospitals Wichita
🇺🇸Wichita, Kansas, United States
Cancer Center of Kansas - Wichita
🇺🇸Wichita, Kansas, United States
Wichita NCI Community Oncology Research Program
🇺🇸Wichita, Kansas, United States
Cancer Center of Kansas - Winfield
🇺🇸Winfield, Kansas, United States
Christus Saint Frances Cabrini Hospital
🇺🇸Alexandria, Louisiana, United States
DeSoto Regional Health System
🇺🇸Mansfield, Louisiana, United States
Ochsner LSU Health Monroe Medical Center
🇺🇸Monroe, Louisiana, United States
Overton Brooks Veteran's Administration Medical Center
🇺🇸Shreveport, Louisiana, United States
LSU Health Sciences Center at Shreveport
🇺🇸Shreveport, Louisiana, United States
Highland Clinic
🇺🇸Shreveport, Louisiana, United States
Boston Medical Center
🇺🇸Boston, Massachusetts, United States
Lahey Hospital and Medical Center
🇺🇸Burlington, Massachusetts, United States
Bronson Battle Creek
🇺🇸Battle Creek, Michigan, United States
Spectrum Health Big Rapids Hospital
🇺🇸Big Rapids, Michigan, United States
Cancer Research Consortium of West Michigan NCORP
🇺🇸Grand Rapids, Michigan, United States
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
🇺🇸Grand Rapids, Michigan, United States
Trinity Health Grand Rapids Hospital
🇺🇸Grand Rapids, Michigan, United States
Trinity Health Muskegon Hospital
🇺🇸Muskegon, Michigan, United States
Corewell Health Reed City Hospital
🇺🇸Reed City, Michigan, United States
Munson Medical Center
🇺🇸Traverse City, Michigan, United States
University Health Truman Medical Center
🇺🇸Kansas City, Missouri, United States
Saint Luke's Hospital of Kansas City
🇺🇸Kansas City, Missouri, United States
Saint Joseph Health Center
🇺🇸Kansas City, Missouri, United States
North Kansas City Hospital
🇺🇸Kansas City, Missouri, United States
Heartland Hematology and Oncology Associates Incorporated
🇺🇸Kansas City, Missouri, United States
Research Medical Center
🇺🇸Kansas City, Missouri, United States
Saint Luke's East - Lee's Summit
🇺🇸Lee's Summit, Missouri, United States
Liberty Hospital
🇺🇸Liberty, Missouri, United States
Mercy Clinic-Rolla-Cancer and Hematology
🇺🇸Rolla, Missouri, United States
Heartland Regional Medical Center
🇺🇸Saint Joseph, Missouri, United States
Saint Louis Cancer and Breast Institute-South City
🇺🇸Saint Louis, Missouri, United States
Mercy Hospital Saint Louis
🇺🇸Saint Louis, Missouri, United States
Cancer Research for the Ozarks NCORP
🇺🇸Springfield, Missouri, United States
Mercy Hospital Springfield
🇺🇸Springfield, Missouri, United States
Billings Clinic Cancer Center
🇺🇸Billings, Montana, United States
Saint Vincent Healthcare
🇺🇸Billings, Montana, United States
Montana Cancer Consortium NCORP
🇺🇸Billings, Montana, United States
Saint Vincent Frontier Cancer Center
🇺🇸Billings, Montana, United States
Bozeman Health Deaconess Hospital
🇺🇸Bozeman, Montana, United States
Saint James Community Hospital and Cancer Treatment Center
🇺🇸Butte, Montana, United States
Benefis Sletten Cancer Institute
🇺🇸Great Falls, Montana, United States
Great Falls Clinic
🇺🇸Great Falls, Montana, United States
Saint Peter's Community Hospital
🇺🇸Helena, Montana, United States
Glacier Oncology PLLC
🇺🇸Kalispell, Montana, United States
Logan Health Medical Center
🇺🇸Kalispell, Montana, United States
Montana Cancer Specialists
🇺🇸Missoula, Montana, United States
Saint Patrick Hospital - Community Hospital
🇺🇸Missoula, Montana, United States
Arnot Ogden Medical Center/Falck Cancer Center
🇺🇸Elmira, New York, United States
Interlakes Foundation Inc-Rochester
🇺🇸Rochester, New York, United States
University of Rochester
🇺🇸Rochester, New York, United States
Wayne Memorial Hospital
🇺🇸Goldsboro, North Carolina, United States
Margaret R Pardee Memorial Hospital
🇺🇸Hendersonville, North Carolina, United States
AdventHealth Hendersonville
🇺🇸Hendersonville, North Carolina, United States
Iredell Memorial Hospital
🇺🇸Statesville, North Carolina, United States
Southeast Clinical Oncology Research Consortium NCORP
🇺🇸Winston-Salem, North Carolina, United States
Mary Rutan Hospital
🇺🇸Bellefontaine, Ohio, United States
Adena Regional Medical Center
🇺🇸Chillicothe, Ohio, United States
University of Cincinnati Cancer Center-UC Medical Center
🇺🇸Cincinnati, Ohio, United States
Riverside Methodist Hospital
🇺🇸Columbus, Ohio, United States
Columbus NCI Community Oncology Research Program
🇺🇸Columbus, Ohio, United States
Grant Medical Center
🇺🇸Columbus, Ohio, United States
Mount Carmel Health Center West
🇺🇸Columbus, Ohio, United States
Doctors Hospital
🇺🇸Columbus, Ohio, United States
Grandview Hospital
🇺🇸Dayton, Ohio, United States
Good Samaritan Hospital - Dayton
🇺🇸Dayton, Ohio, United States
Miami Valley Hospital
🇺🇸Dayton, Ohio, United States
Miami Valley Hospital North
🇺🇸Dayton, Ohio, United States
Dayton NCI Community Oncology Research Program
🇺🇸Dayton, Ohio, United States
Grady Memorial Hospital
🇺🇸Delaware, Ohio, United States
Blanchard Valley Hospital
🇺🇸Findlay, Ohio, United States
Atrium Medical Center-Middletown Regional Hospital
🇺🇸Franklin, Ohio, United States
Wayne Hospital
🇺🇸Greenville, Ohio, United States
Kettering Medical Center
🇺🇸Kettering, Ohio, United States
Fairfield Medical Center
🇺🇸Lancaster, Ohio, United States
Marietta Memorial Hospital
🇺🇸Marietta, Ohio, United States
Knox Community Hospital
🇺🇸Mount Vernon, Ohio, United States
Licking Memorial Hospital
🇺🇸Newark, Ohio, United States
Southern Ohio Medical Center
🇺🇸Portsmouth, Ohio, United States
Springfield Regional Medical Center
🇺🇸Springfield, Ohio, United States
Upper Valley Medical Center
🇺🇸Troy, Ohio, United States
Saint Ann's Hospital
🇺🇸Westerville, Ohio, United States
Wright-Patterson Medical Center
🇺🇸Wright-Patterson Air Force Base, Ohio, United States
Greene Memorial Hospital
🇺🇸Xenia, Ohio, United States
Genesis Healthcare System Cancer Care Center
🇺🇸Zanesville, Ohio, United States
Saint Charles Health System
🇺🇸Bend, Oregon, United States
AnMed Health Cancer Center
🇺🇸Anderson, South Carolina, United States
AnMed Health Hospital
🇺🇸Anderson, South Carolina, United States
Saint Francis Hospital
🇺🇸Greenville, South Carolina, United States
Spartanburg Medical Center
🇺🇸Spartanburg, South Carolina, United States
Cancer Care Center at Island Hospital
🇺🇸Anacortes, Washington, United States
PeaceHealth Saint Joseph Medical Center
🇺🇸Bellingham, Washington, United States
Highline Medical Center-Main Campus
🇺🇸Burien, Washington, United States
Swedish Cancer Institute-Edmonds
🇺🇸Edmonds, Washington, United States
Swedish Cancer Institute-Issaquah
🇺🇸Issaquah, Washington, United States
Kadlec Clinic Hematology and Oncology
🇺🇸Kennewick, Washington, United States
Skagit Valley Hospital
🇺🇸Mount Vernon, Washington, United States
Harrison HealthPartners Hematology and Oncology-Poulsbo
🇺🇸Poulsbo, Washington, United States
Harborview Medical Center
🇺🇸Seattle, Washington, United States
Minor and James Medical PLLC
🇺🇸Seattle, Washington, United States
Fred Hutchinson Cancer Center
🇺🇸Seattle, Washington, United States
Kaiser Permanente Washington
🇺🇸Seattle, Washington, United States
Swedish Medical Center-First Hill
🇺🇸Seattle, Washington, United States
University of Washington Medical Center - Montlake
🇺🇸Seattle, Washington, United States
PeaceHealth United General Medical Center
🇺🇸Sedro-Woolley, Washington, United States
Saint Michael Cancer Center
🇺🇸Silverdale, Washington, United States
Cancer Care Northwest - Spokane South
🇺🇸Spokane, Washington, United States
Evergreen Hematology and Oncology PS
🇺🇸Spokane, Washington, United States
Wenatchee Valley Hospital and Clinics
🇺🇸Wenatchee, Washington, United States
Rocky Mountain Oncology
🇺🇸Casper, Wyoming, United States
Welch Cancer Center
🇺🇸Sheridan, Wyoming, United States