Immunotherapy (Nivolumab or Brentuximab Vedotin) Plus Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage III-IV Classic Hodgkin Lymphoma

Classic Hodgkin Lymphoma Clinical Trial

Official title:

A Phase III, Randomized Study of Nivolumab (Opdivo) Plus AVD or Brentuximab Vedotin (Adcetris) Plus AVD in Patients (Age >/= 12 Years) With Newly Diagnosed Advanced Stage Classical Hodgkin Lymphoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03907488
• Other study ID #: NCI-2019-01960
• Secondary ID: NCI-2019-01960S1
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: August 29, 2019
• Est. completion date: April 1, 2025

Study information

• Verified date: April 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase III trial compares immunotherapy drugs (nivolumab or brentuximab vedotin) when given with combination chemotherapy in treating patients with newly diagnosed stage III or IV classic Hodgkin lymphoma. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to cancer cells in a targeted way and delivers vedotin to kill them. Chemotherapy drugs, such as doxorubicin, vinblastine, and dacarbazine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. The addition of nivolumab or brentuximab vedotin to combination chemotherapy may shrink the cancer or extend the time without disease symptoms coming back.

Description:

PRIMARY OBJECTIVE: I. To compare the progression-free survival (PFS) in patients with newly diagnosed advanced stage classical Hodgkin lymphoma randomized to N-AVD (nivolumab, doxorubicin hydrochloride [doxorubicin], vinblastine sulfate [vinblastine], dacarbazine) versus that obtained with BV-AVD (brentuximab vedotin, doxorubicin, vinblastine, dacarbazine). SECONDARY OBJECTIVES: I. To compare overall survival (OS) in patients randomized to N-AVD versus BV-AVD. II. To compare event-free survival (EFS) in patients randomized to N-AVD versus BV-AVD. III. To compare the metabolic complete response (CR) rate at the end of treatment in patients randomized to N-AVD versus BV-AVD. IV. To compare the physician-reported treatment-related adverse event rates between arms stratified by age groups. V. To compare patient-reported symptoms using selected Patient Reported Outcome Common Toxicity Criteria for Adverse Events (PRO-CTCAE) items between arms stratified by age groups. VI. To compare the safety and tolerability of N-AVD versus that of BV-AVD. QUALITY OF LIFE OBJECTIVE: I. To compare between arms patient-reported fatigue, neuropathy and health-related quality of life over time (baseline, beginning of cycle 3, 4-8 weeks after the last dose of protocol therapy [following last dose of study drug or radiation therapy, whichever is later], and 1 and 3 years after randomization) using the Patient Reported Outcomes Measurement Information System (PROMIS)-Fatigue, the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx), and the PROMIS Global, respectively. BANKING OBJECTIVES: I. To bank specimens for future correlative studies. II. To bank positron emission tomography (PET)-computed tomography (CT) images for future correlative studies. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive doxorubicin hydrochloride intravenously (IV), vinblastine sulfate IV, dacarbazine IV, and nivolumab IV over 30 minutes on days 1 and 15. Patients may receive pegfilgrastim subcutaneously (SC) on days 2 and 16, or filgrastim SC or IV on days 6-10 and 21-25. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of cycle 6, patients may receive radiation therapy 5 days per week for approximately 4 weeks at the discretion of the treating physician. Patients also undergo peripheral blood specimen collection and CT, PET/CT and/or magnetic resonance imaging (MRI) on study. ARM II: Patients receive doxorubicin hydrochloride IV, vinblastine sulfate IV, dacarbazine IV, and brentuximab vedotin IV over 30 minutes on days 1 and 15. Patients may receive pegfilgrastim SC on days 2 and 16, or filgrastim SC or IV on days 6-10 and 21-25. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of cycle 6, patients may receive radiation therapy 5 days per week for approximately 4 weeks at the discretion of the treating physician. Patients also undergo peripheral blood specimen collection and CT, PET/CT and MRI on study. After completion of study treatment and prior to disease progression, patients are followed up every 3 months for the first year, every 6 months for years 2 and 3, then annually until 10 years after registration. Patients are followed up at the time of progression and then annually until 10 years after registration. Patients who receive radiation therapy are followed up at 8-12 weeks after completion of radiation therapy.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 995
• Est. completion date: April 1, 2025
• Est. primary completion date: March 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• All patients must have histologically confirmed newly diagnosed, previously untreated stage III or IV classical Hodgkin lymphoma (nodular sclerosing, mixed cellularity, lymphocyte-rich, or lymphocyte-depleted, or not otherwise specified [NOS]). Nodular lymphocyte predominant Hodgkin lymphoma is not eligible.
• Patients must have bidimensionally measurable disease (at least one lesion with longest diameter >= 1.5 cm) documented on the Lymphoma Baseline Tumor Assessment Form in Rave.
• Patients must have a whole body or limited whole body PET-CT scan performed within 42 days prior to registration. (A contrast-enhanced [diagnostic] CT, MRI or MR-PET is acceptable in event that PET-CT is contra-indicated, however if it is later possible to administer a PET-CT, then PET-CT is strongly preferred for the interim scan (after cycle 2) (if performed) and the EOT assessment. Otherwise, if PET-CT is not subsequently possible, then the same modality as baseline must be used throughout the trial.) NOTE: All images from PET-CT, CT, MRI or MR-PET scans performed as standard of care to assess disease (within 42 days prior to registration) must be submitted and associated radiology reports must be submitted.
• Patients must be >= 12 years of age.
• Patients must not have received any prior chemotherapy, radiation, or antibody-based treatment for classical Hodgkin lymphoma. Steroid pre-treatment is permitted.
• Patients must not have had prior solid organ transplant.
• Patients must not have had prior allogeneic stem cell transplantation.
• Patients must not have received a live vaccine within 30 days prior to planned day 1 of protocol therapy (e.g. measles, mumps, rubella, varicella, yellow fever, rabies, Bacillus Calmette-Guerin [BCG], oral polio vaccine, and oral typhoid).
• At registration, investigator must declare intent-to-treat with residual PET radiation therapy (residual PET RT- RPRT) to be administered after patient completes 6 cycles of therapy if, after end of treatment, the patient meets criteria specified for receiving RT). Patients will be stratified by investigator's intent-to-treat with residual PET RT.
• All pediatric patients (< 18 years of age) will be considered intent-to-treat with Residual PET RT at time of registration.
• Patients must have a performance status corresponding to Zubrod scores of 0, 1 or 2. Use Lansky for patients =< 17 years of age. *The conversion of the Lansky to Eastern Cooperative Oncology Group (ECOG) scales is intended for National Cancer Institute (NCI) reporting purposes only.
• Adults (age 18 or older): Creatinine clearance >= 30 mL/min, as estimated by the Cockcroft and Gault formula. The creatinine value used in the calculation must have been obtained within 28 days prior to registration. Estimated creatinine clearance is based on actual body weight. Pediatric Patients (age 12-17), the following must have been obtained within 14 days prior

to registration:

• Measured or calculated creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2, or
• Serum creatinine =< 1.5 x institutional upper limit of normal (IULN), or a serum

creatinine (SCr) based on age/gender as follows:

• Age < 13 maximum serum creatinine: Male 1.2 mg/dL; Female 1.2 mg/dL
• Age 13 to < 16 maximum serum creatinine: Male 1.5 mg/dL; Female 1.4 mg/dL
• Age 16-17 maximum serum creatinine: Male 1.7 mg/dL; Female 1.4 mg/dL
• Total bilirubin =< 2 x IULN (must be documented within 28 days prior to registration for adults [age 18 or older]; must be documented within 14 days prior to registration for pediatric patients [age 12-17]).
• Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing bile duct syndrome
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x IULN (must be documented within 28 days prior to registration for adults [age 18 or older]; must be documented within 14 days prior to registration for pediatric patients [age 12-17]).
• Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing bile duct syndrome
• Patients must have an echocardiogram (ECHO), multigated acquisition (MUGA), or functional cardiac imaging scan with a left ventricular ejection (LVEF) fraction >= 50% or a shortening fraction of >= 27%. For all patients, the ECHO, MUGA, or functional cardiac imaging scan must be performed within 42 days prior to registration.
• Patients with known human immunodeficiency virus (HIV) infection must be receiving anti-retroviral therapy and have an undetectable or unquantifiable viral load at their most recent viral load test within 6 months prior to registration.
• Patients must not have known active hepatitis B (HBV) or hepatitis C virus (HCV) at date of registration. Patients with previously treated HBV or HCV that have an undetectable viral load within 6 months prior to registration and no residual hepatic impairment are eligible.
• Patients must not have any known central nervous system lymphoma.
• Patients must not have a history of or active interstitial pneumonitis or interstitial lung disease.
• Patients must not have had a diagnosis of inherited or acquired immunodeficiency.
• Patients must not have any known uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, hemodynamically unstable cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients must not have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to registration. Inhaled or topical steroids, and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Steroid use for the control of Hodgkin lymphoma symptoms is allowable, but must be discontinued prior to cycle 1, day 1.
• Patients with peripheral neuropathy must have < grade 2 at date of registration.
• Patients must not have active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, immunosuppressive drugs, or corticosteroids with doses higher than prednisone 10 mg or equivalent). Autoimmune diseases include but are not limited to autoimmune hepatitis, inflammatory bowel disease (including ulcerative colitis and Crohn's disease), as well as symptomatic disease (e.g.: rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's granulomatosis]); central nervous system (CNS) or motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and myasthenia gravis, multiple sclerosis or glomerulonephritis). Vitiligo, alopecia, hypothyroidism on stable doses of thyroid replacement therapy, psoriasis not requiring systemic therapy within the past 2 years are permitted.
• No second prior malignancy is allowed except for adequately treated basal (or squamous cell) skin cancer, any in situ cancer or other cancer for which the patient has been disease free for two years.
• Females of childbearing potential must not be pregnant or nursing, and have a negative pregnancy test within 28 days prior to registration. Women/men of reproductive potential must have agreed to use an effective contraceptive method while receiving study drug and for women until 6 months after receiving the last dose of study drug or, for men, until 7 months after receiving the last dose of study drug. 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.
• Patients must have one formalin-fixed paraffin embedded (FFPE) diagnostic tumor block or at least 1 diagnostic, 4-5 micron, hematoxylin and eosin (H&E) slide collected prior to registration and available for submission.
• Patients must be offered participation in banking for planned translational medicine and future research. With patient consent, any residuals from the mandatory tissue submission will also be banked for future research.
• Patients who can complete Patient-Reported Outcome instruments in English, Spanish, or French must complete the PROMIS Fatigue, the FACT/GOG-Ntx, and the PROMIS Global prior to registration. Patients who do not complete PRO instruments prior to registration but are otherwise eligible will remain eligible for the primary analysis and other secondary analyses.
• Patients who can complete Patient-Reported Outcome instruments in English, Spanish, or French must also agree to complete the PROMIS Fatigue, the FACT/GOG-Ntx, the PROMIS Global, and the PRO-CTCAE (or Pediatric [Ped] PRO-CTCAE) at the scheduled on-study assessment timepoints.
• Patients must be informed of the investigational nature of this study and all patients and/or their parents or legal guardians (for patients < 18 years of age) must sign and give informed consent and assent (where appropriate) in accordance with institutional and federal guidelines. For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board Initiative (CIRB) regulations.
• Note: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.

Related Conditions & MeSH terms

• Ann Arbor Stage III Hodgkin Lymphoma
• Ann Arbor Stage III Lymphocyte-Depleted Classic Hodgkin Lymphoma
• Ann Arbor Stage III Mixed Cellularity Classic Hodgkin Lymphoma
• Ann Arbor Stage III Nodular Sclerosis Classic Hodgkin Lymphoma
• Ann Arbor Stage IV Hodgkin Lymphoma
• Ann Arbor Stage IV Lymphocyte-Depleted Classic Hodgkin Lymphoma
• Ann Arbor Stage IV Mixed Cellularity Classic Hodgkin Lymphoma
• Ann Arbor Stage IV Nodular Sclerosis Classic Hodgkin Lymphoma
• Classic Hodgkin Lymphoma
• Hodgkin Disease
• Lymphocyte-Rich Classic Hodgkin Lymphoma
• Lymphoma
• Sclerosis

Intervention

Procedure:
• Biospecimen Collection
Undergo peripheral blood collection

Drug:
• Brentuximab Vedotin
Given IV

Procedure:
• Computed Tomography
Undergo PET/CT or CT scan

Drug:
• Dacarbazine
Given IV
• Doxorubicin Hydrochloride
Given IV

Biological:
• Filgrastim
Given SC or IV

Procedure:
• Magnetic Resonance Imaging
Undergo MRI

Biological:
• Nivolumab
Given IV
• Pegfilgrastim
Given SC

Procedure:
• Positron Emission Tomography
Undergo PET/CT scan

Other:
• Quality-of-Life Assessment
Ancillary studies
• Questionnaire Administration
Ancillary studies

Radiation:
• Radiation Therapy
Receive radiation therapy

Drug:
• Vinblastine Sulfate
Given IV

Locations

Country	Name	City	State
Canada	William Osler Health System-Brampton Civic Hospital	Brampton	Ontario
Canada	QEII Health Sciences Centre/Nova Scotia Health Authority	Halifax	Nova Scotia
Canada	Kingston Health Sciences Centre	Kingston	Ontario
Canada	Centre Hospitalier Universitaire Sainte-Justine	Montreal	Quebec
Canada	The Montreal Children's Hospital of the MUHC	Montreal	Quebec
Canada	The Research Institute of the McGill University Health Centre (MUHC)	Montreal	Quebec
Canada	Ottawa Hospital and Cancer Center-General Campus	Ottawa	Ontario
Canada	CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)	Quebec
Canada	CHA Hopital L'Enfant-Jesus	Quebec City	Quebec
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Atlantic Health Sciences Corporation-Saint John Regional Hospital	Saint John	New Brunswick
Canada	Hospital for Sick Children	Toronto	Ontario
Canada	University Health Network-Princess Margaret Hospital	Toronto	Ontario
Canada	BCCA-Vancouver Cancer Centre	Vancouver	British Columbia
Canada	BCCA-Vancouver Island Cancer Centre	Victoria	British Columbia
Puerto Rico	HIMA San Pablo Oncologic Hospital	Caguas
Puerto Rico	University Pediatric Hospital	San Juan
United States	Hawaii Cancer Care - Westridge	'Aiea	Hawaii
United States	Pali Momi Medical Center	'Aiea	Hawaii
United States	Queen's Cancer Center - Pearlridge	'Aiea	Hawaii
United States	The Cancer Center of Hawaii-Pali Momi	'Aiea	Hawaii
United States	Providence Regional Cancer System-Aberdeen	Aberdeen	Washington
United States	Children's Hospital Medical Center of Akron	Akron	Ohio
United States	Albany Medical Center	Albany	New York
United States	Atrium Health Stanly/LCI-Albemarle	Albemarle	North Carolina
United States	Presbyterian Hospital	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania
United States	McFarland Clinic - Ames	Ames	Iowa
United States	Kaiser Permanente-Anaheim	Anaheim	California
United States	Alaska Breast Care and Surgery LLC	Anchorage	Alaska
United States	Alaska Oncology and Hematology LLC	Anchorage	Alaska
United States	Alaska Women's Cancer Care	Anchorage	Alaska
United States	Anchorage Associates in Radiation Medicine	Anchorage	Alaska
United States	Anchorage Oncology Centre	Anchorage	Alaska
United States	Katmai Oncology Group	Anchorage	Alaska
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	C S Mott Children's Hospital	Ann Arbor	Michigan
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Kaiser Permanente-Deer Valley Medical Center	Antioch	California
United States	Ascension Saint Elizabeth Hospital	Appleton	Wisconsin
United States	ThedaCare Regional Cancer Center	Appleton	Wisconsin
United States	PCR Oncology	Arroyo Grande	California
United States	Duluth Clinic Ashland	Ashland	Wisconsin
United States	Northwest Wisconsin Cancer Center	Ashland	Wisconsin
United States	Children's Healthcare of Atlanta - Egleston	Atlanta	Georgia
United States	Emory Saint Joseph's Hospital	Atlanta	Georgia
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Augusta University Medical Center	Augusta	Georgia
United States	Harold Alfond Center for Cancer Care	Augusta	Maine
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Rocky Mountain Cancer Centers-Aurora	Aurora	Colorado
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	The Medical Center of Aurora	Aurora	Colorado
United States	UCHealth University of Colorado Hospital	Aurora	Colorado
United States	Dell Children's Medical Center of Central Texas	Austin	Texas
United States	Kaiser Permanente-Baldwin Park	Baldwin Park	California
United States	Saint Louis Cancer and Breast Institute-Ballwin	Ballwin	Missouri
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	MaineHealth Coastal Cancer Treatment Center	Bath	Maine
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	UM Upper Chesapeake Medical Center	Bel Air	Maryland
United States	Waldo County General Hospital	Belfast	Maine
United States	Nebraska Medicine-Bellevue	Bellevue	Nebraska
United States	Overlake Medical Center	Bellevue	Washington
United States	Kaiser Permanente-Bellflower	Bellflower	California
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	Saint Charles Health System	Bend	Oregon
United States	Walter Reed National Military Medical Center	Bethesda	Maryland
United States	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania
United States	Tower Cancer Research Foundation	Beverly Hills	California
United States	MaineHealth/SMHC Cancer Care and Blood Disorders-Biddeford	Biddeford	Maine
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	Children's Hospital of Alabama	Birmingham	Alabama
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Central Care Cancer Center - Bolivar	Bolivar	Missouri
United States	Parkland Health Center-Bonne Terre	Bonne Terre	Missouri
United States	Boston Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Tufts Children's Hospital	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Boulder Community Foothills Hospital	Boulder	Colorado
United States	Boulder Community Hospital	Boulder	Colorado
United States	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Essentia Health Saint Joseph's Medical Center	Brainerd	Minnesota
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Harrison Medical Center	Bremerton	Washington
United States	Saint Joseph Mercy Brighton	Brighton	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Brighton	Brighton	Michigan
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Ascension Southeast Wisconsin Hospital - Elmbrook Campus	Brookfield	Wisconsin
United States	New York-Presbyterian/Brooklyn Methodist Hospital	Brooklyn	New York
United States	Henry Ford Cancer Institute-Downriver	Brownstown	Michigan
United States	Saint Joseph Regional Cancer Center	Bryan	Texas
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin
United States	University of Vermont and State Agricultural College	Burlington	Vermont
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Minnesota Oncology - Burnsville	Burnsville	Minnesota
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Cleveland Clinic Mercy Hospital	Canton	Ohio
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Joseph Mercy Canton	Canton	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Canton	Canton	Michigan
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Memorial Hospital of Carbondale	Carbondale	Illinois
United States	Saint Anthony Regional Hospital	Carroll	Iowa
United States	SIH Cancer Institute	Carterville	Illinois
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Sandra L Maxwell Cancer Center	Cedar City	Utah
United States	Mercy Hospital	Cedar Rapids	Iowa
United States	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Providence Regional Cancer System-Centralia	Centralia	Washington
United States	Christiana Care Health System-Concord Health Center	Chadds Ford	Pennsylvania
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	West Virginia University Charleston Division	Charleston	West Virginia
United States	Atrium Health Pineville/LCI-Pineville	Charlotte	North Carolina
United States	Atrium Health University City/LCI-University	Charlotte	North Carolina
United States	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina
United States	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
United States	T C Thompson Children's Hospital	Chattanooga	Tennessee
United States	Saint Joseph Mercy Chelsea	Chelsea	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital	Chelsea	Michigan
United States	Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Ascension Calumet Hospital	Chilton	Wisconsin
United States	Bethesda North Hospital	Cincinnati	Ohio
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	University of Cincinnati Cancer Center-UC Medical Center	Cincinnati	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon
United States	Wake Forest University at Clemmons	Clemmons	North Carolina
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Rainbow Babies and Childrens Hospital	Cleveland	Ohio
United States	Henry Ford Macomb Hospital-Clinton Township	Clinton Township	Michigan
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Kootenai Health - Coeur d'Alene	Coeur d'Alene	Idaho
United States	Baptist Memorial Hospital and Cancer Center-Collierville	Collierville	Tennessee
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado
United States	Prisma Health Richland Hospital	Columbia	South Carolina
United States	Baptist Memorial Hospital and Cancer Center-Golden Triangle	Columbus	Mississippi
United States	Doctors Hospital	Columbus	Ohio
United States	Grant Medical Center	Columbus	Ohio
United States	Mount Carmel East Hospital	Columbus	Ohio
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	The Mark H Zangmeister Center	Columbus	Ohio
United States	Atrium Health Cabarrus/LCI-Concord	Concord	North Carolina
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Bay Area Hospital	Coos Bay	Oregon
United States	UM Sylvester Comprehensive Cancer Center at Coral Gables	Coral Gables	Florida
United States	Driscoll Children's Hospital	Corpus Christi	Texas
United States	Greater Regional Medical Center	Creston	Iowa
United States	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri
United States	Medical City Dallas Hospital	Dallas	Texas
United States	Carle at The Riverfront	Danville	Illinois
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Beaumont Hospital - Dearborn	Dearborn	Michigan
United States	Henry Ford Medical Center-Fairlane	Dearborn	Michigan
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Essentia Health - Deer River Clinic	Deer River	Minnesota
United States	Northwestern Medicine Cancer Center Kishwaukee	DeKalb	Illinois
United States	Delaware Health Center-Grady Cancer Center	Delaware	Ohio
United States	Kaiser Permanente-Franklin	Denver	Colorado
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado
United States	Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center	Denver	Colorado
United States	SCL Health Saint Joseph Hospital	Denver	Colorado
United States	Smilow Cancer Hospital-Derby Care Center	Derby	Connecticut
United States	Blank Children's Hospital	Des Moines	Iowa
United States	Broadlawns Medical Center	Des Moines	Iowa
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	Des Moines	Iowa
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Essentia Health Saint Mary's - Detroit Lakes Clinic	Detroit Lakes	Minnesota
United States	Illinois CancerCare-Dixon	Dixon	Illinois
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Dublin Methodist Hospital	Dublin	Ohio
United States	Kaiser Permanente Dublin	Dublin	California
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota
United States	Miller-Dwan Hospital	Duluth	Minnesota
United States	Duke University Medical Center	Durham	North Carolina
United States	Hematology Oncology Associates of Central New York-East Syracuse	East Syracuse	New York
United States	HSHS Sacred Heart Hospital	Eau Claire	Wisconsin
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Mayo Clinic Health System Eau Claire Hospital-Luther Campus	Eau Claire	Wisconsin
United States	Mayo Clinic Health System-Eau Claire Clinic	Eau Claire	Wisconsin
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	STCC at DHR Health Institute for Research and Development	Edinburg	Texas
United States	Swedish Cancer Institute-Edmonds	Edmonds	Washington
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	El Paso Children's Hospital	El Paso	Texas
United States	Mountain Blue Cancer Care Center - Swedish	Englewood	Colorado
United States	Swedish Medical Center	Englewood	Colorado
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Fairbanks Memorial Hospital	Fairbanks	Alaska
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Essentia Health Cancer Center-South University Clinic	Fargo	North Dakota
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Parkland Health Center - Farmington	Farmington	Missouri
United States	Weisberg Cancer Treatment Center	Farmington Hills	Michigan
United States	Lake Region Healthcare Corporation-Cancer Care	Fergus Falls	Minnesota
United States	Kaiser Permanente-Fontana	Fontana	California
United States	Broward Health Medical Center	Fort Lauderdale	Florida
United States	Golisano Children's Hospital of Southwest Florida	Fort Myers	Florida
United States	Regional Cancer Center-Lee Memorial Health System	Fort Myers	Florida
United States	Mercy Hospital Fort Smith	Fort Smith	Arkansas
United States	Parkview Regional Medical Center	Fort Wayne	Indiana
United States	Essentia Health - Fosston	Fosston	Minnesota
United States	Beebe South Coastal Health Campus	Frankford	Delaware
United States	Ascension Saint Francis - Reiman Cancer Center	Franklin	Wisconsin
United States	Ascension Southeast Wisconsin Hospital - Franklin	Franklin	Wisconsin
United States	Kaiser Permanente-Fremont	Fremont	California
United States	Kaiser Permanente-Fresno	Fresno	California
United States	Unity Hospital	Fridley	Minnesota
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
United States	Gibbs Cancer Center-Gaffney	Gaffney	South Carolina
United States	University of Florida Health Science Center - Gainesville	Gainesville	Florida
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Western Illinois Cancer Treatment Center	Galesburg	Illinois
United States	Central Care Cancer Center - Garden City	Garden City	Kansas
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	Aurora Health Care Germantown Health Center	Germantown	Wisconsin
United States	Glens Falls Hospital	Glens Falls	New York
United States	NorthShore University HealthSystem-Glenbrook Hospital	Glenview	Illinois
United States	Peninsula Cancer Institute-Gloucester	Gloucester	Virginia
United States	CTCA at Western Regional Medical Center	Goodyear	Arizona
United States	Aurora Cancer Care-Grafton	Grafton	Wisconsin
United States	CHI Health Saint Francis	Grand Island	Nebraska
United States	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado
United States	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Trinity Health Grand Rapids Hospital	Grand Rapids	Michigan
United States	Central Care Cancer Center - Great Bend	Great Bend	Kansas
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	North Colorado Medical Center	Greeley	Colorado
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin
United States	BI-LO Charities Children's Cancer Center	Greenville	South Carolina
United States	East Carolina University	Greenville	North Carolina
United States	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Faris	Greenville	South Carolina
United States	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina
United States	Saint Francis Cancer Center	Greenville	South Carolina
United States	Saint Francis Hospital	Greenville	South Carolina
United States	Gibbs Cancer Center-Pelham	Greer	South Carolina
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	Baptist Cancer Center-Grenada	Grenada	Mississippi
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Kaiser Permanente - Harbor City	Harbor City	California
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania
United States	Comprehensive Cancer Centers of Nevada - Henderson	Henderson	Nevada
United States	OptumCare Cancer Care at Seven Hills	Henderson	Nevada
United States	Essentia Health Hibbing Clinic	Hibbing	Minnesota
United States	NorthShore University HealthSystem-Highland Park Hospital	Highland Park	Illinois
United States	AMITA Health Cancer Institute and Outpatient Center	Hinsdale	Illinois
United States	Memorial Regional Hospital/Joe DiMaggio Children's Hospital	Hollywood	Florida
United States	UM Sylvester Comprehensive Cancer Center at Hollywood	Hollywood	Florida
United States	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii
United States	Hawaii Cancer Care Inc-Liliha	Honolulu	Hawaii
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Kuakini Medical Center	Honolulu	Hawaii
United States	Queen's Cancer Cenrer - POB I	Honolulu	Hawaii
United States	Queen's Cancer Center - Kuakini	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	CHI Saint Vincent Cancer Center Hot Springs	Hot Springs	Arkansas
United States	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas
United States	M D Anderson Cancer Center	Houston	Texas
United States	Ascension Saint Vincent Indianapolis Hospital	Indianapolis	Indiana
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Kaiser Permanente-Irvine	Irvine	California
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	Allegiance Health	Jackson	Michigan
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Nemours Children's Clinic-Jacksonville	Jacksonville	Florida
United States	Essentia Health - Jamestown Clinic	Jamestown	North Dakota
United States	Capital Region Southwest Campus	Jefferson City	Missouri
United States	Duly Health and Care Joliet	Joliet	Illinois
United States	NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro	Jonesboro	Arkansas
United States	Freeman Health System	Joplin	Missouri
United States	Mercy Hospital Joplin	Joplin	Missouri
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Children's Mercy Hospitals and Clinics	Kansas City	Missouri
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	University of Kansas Cancer Center - North	Kansas City	Missouri
United States	University of Kansas Cancer Center-West	Kansas City	Kansas
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Vidant Oncology-Kenansville	Kenansville	North Carolina
United States	Ochsner Medical Center Kenner	Kenner	Louisiana
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin
United States	Novant Health Cancer Institute - Kernersville	Kernersville	North Carolina
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Vidant Oncology-Kinston	Kinston	North Carolina
United States	East Tennessee Childrens Hospital	Knoxville	Tennessee
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Providence Regional Cancer System-Lacey	Lacey	Washington
United States	Kaiser Permanente-Rock Creek	Lafayette	Colorado
United States	Northwestern Medicine Lake Forest Hospital	Lake Forest	Illinois
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Alliance for Childhood Diseases/Cure 4 the Kids Foundation	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Northwest	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Town Center	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada-Summerlin	Las Vegas	Nevada
United States	GenesisCare USA - Las Vegas	Las Vegas	Nevada
United States	OptumCare Cancer Care at Charleston	Las Vegas	Nevada
United States	OptumCare Cancer Care at Fort Apache	Las Vegas	Nevada
United States	OptumCare Cancer Care at MountainView	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Southeast	Las Vegas	Nevada
United States	Cancer Centers of Southwest Oklahoma Research	Lawton	Oklahoma
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	University of Kansas Cancer Center - Lee's Summit	Lee's Summit	Missouri
United States	Beebe Medical Center	Lewes	Delaware
United States	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania
United States	Lewistown Hospital	Lewistown	Pennsylvania
United States	Saint Joseph Hospital East	Lexington	Kentucky
United States	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii
United States	Saint Rita's Medical Center	Lima	Ohio
United States	Atrium Health Lincoln/LCI-Lincolnton	Lincolnton	North Carolina
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Rocky Mountain Cancer Centers-Littleton	Littleton	Colorado
United States	Saint Barnabas Medical Center	Livingston	New Jersey
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	Logan Regional Hospital	Logan	Utah
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Kaiser Permanente-Lone Tree	Lone Tree	Colorado
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Longmont United Hospital	Longmont	Colorado
United States	PeaceHealth Saint John Medical Center	Longview	Washington
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Kaiser Permanente West Los Angeles	Los Angeles	California
United States	Jewish Hospital	Louisville	Kentucky
United States	Norton Children's Hospital	Louisville	Kentucky
United States	Norton Suburban Hospital and Medical Campus	Louisville	Kentucky
United States	UofL Health Medical Center Northeast	Louisville	Kentucky
United States	McKee Medical Center	Loveland	Colorado
United States	Palms West Radiation Therapy	Loxahatchee Groves	Florida
United States	Covenant Children's Hospital	Lubbock	Texas
United States	UMC Cancer Center / UMC Health System	Lubbock	Texas
United States	Centra Lynchburg Hematology-Oncology Clinic Inc	Lynchburg	Virginia
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Valley Children's Hospital	Madera	California
United States	Dean Hematology and Oncology Clinic	Madison	Wisconsin
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	OhioHealth Mansfield Hospital	Mansfield	Ohio
United States	Fairview Clinics and Surgery Center Maple Grove	Maple Grove	Minnesota
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Fremont - Rideout Cancer Center	Marysville	California
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Loyola University Medical Center	Maywood	Illinois
United States	Baptist Memorial Hospital and Cancer Center-Memphis	Memphis	Tennessee
United States	Ascension Columbia Saint Mary's Hospital Ozaukee	Mequon	Wisconsin
United States	Idaho Urologic Institute-Meridian	Meridian	Idaho
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	Miami Cancer Institute	Miami	Florida
United States	Nicklaus Children's Hospital	Miami	Florida
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Ascension Columbia Saint Mary's Hospital - Milwaukee	Milwaukee	Wisconsin
United States	Ascension Saint Francis Hospital	Milwaukee	Wisconsin
United States	Ascension Southeast Wisconsin Hospital - Saint Joseph Campus	Milwaukee	Wisconsin
United States	Aurora Cancer Care-Milwaukee	Milwaukee	Wisconsin
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Aurora Sinai Medical Center	Milwaukee	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	NYU Winthrop Hospital	Mineola	New York
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Children's Hospitals and Clinics of Minnesota - Minneapolis	Minneapolis	Minnesota
United States	Health Partners Inc	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	University of Minnesota/Masonic Cancer Center	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Community Medical Hospital	Missoula	Montana
United States	University of South Alabama Mitchell Cancer Institute	Mobile	Alabama
United States	USA Health Strada Patient Care Center	Mobile	Alabama
United States	Kaiser Permanente-Modesto	Modesto	California
United States	Monticello Cancer Center	Monticello	Minnesota
United States	Morristown Medical Center	Morristown	New Jersey
United States	Novant Health Cancer Institute - Mount Airy	Mount Airy	North Carolina
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	ProHealth D N Greenwald Center	Mukwonago	Wisconsin
United States	Intermountain Medical Center	Murray	Utah
United States	Trinity Health Muskegon Hospital	Muskegon	Michigan
United States	Saint Alphonsus Cancer Care Center-Nampa	Nampa	Idaho
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	Dartmouth Cancer Center - Nashua	Nashua	New Hampshire
United States	The Children's Hospital at TriStar Centennial	Nashville	Tennessee
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	Baptist Memorial Hospital and Cancer Center-Union County	New Albany	Mississippi
United States	Froedtert and MCW Moorland Reserve Health Center	New Berlin	Wisconsin
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital	New Brunswick	New Jersey
United States	Saint Peter's University Hospital	New Brunswick	New Jersey
United States	Smilow Cancer Center/Yale-New Haven Hospital	New Haven	Connecticut
United States	Yale University	New Haven	Connecticut
United States	UC Comprehensive Cancer Center at Silver Cross	New Lenox	Illinois
United States	Children's Hospital New Orleans	New Orleans	Louisiana
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	Cancer Center of Western Wisconsin	New Richmond	Wisconsin
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York
United States	NYP/Weill Cornell Medical Center	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Licking Memorial Hospital	Newark	Ohio
United States	Medical Oncology Hematology Consultants PA	Newark	Delaware
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Newark Radiation Oncology	Newark	Ohio
United States	Rutgers New Jersey Medical School	Newark	New Jersey
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Peninsula Cancer Institute-Newport News	Newport News	Virginia
United States	Corewell Health Lakeland Hospitals - Niles Hospital	Niles	Michigan
United States	Children's Hospital of The King's Daughters	Norfolk	Virginia
United States	University of Kansas Cancer Center at North Kansas City Hospital	North Kansas City	Missouri
United States	Cancer and Hematology Centers of Western Michigan - Norton Shores	Norton Shores	Michigan
United States	Ascension Providence Hospitals - Novi	Novi	Michigan
United States	Henry Ford Medical Center-Columbus	Novi	Michigan
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	Advocate Children's Hospital-Oak Lawn	Oak Lawn	Illinois
United States	Kaiser Permanente-Oakland	Oakland	California
United States	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Oconto Falls	Oconto Falls	Wisconsin
United States	McKay-Dee Hospital Center	Ogden	Utah
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Immanuel Medical Center	Omaha	Nebraska
United States	Alegent Health Lakeside Hospital	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Nebraska Medicine-Village Pointe	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Kaiser Permanente-Ontario	Ontario	California
United States	Children's Hospital of Orange County	Orange	California
United States	Smilow Cancer Hospital-Orange Care Center	Orange	Connecticut
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	University of Chicago Medicine-Orland Park	Orland Park	Illinois
United States	Nemours Children's Hospital	Orlando	Florida
United States	Orlando Health Cancer Institute	Orlando	Florida
United States	Ascension Mercy Hospital	Oshkosh	Wisconsin
United States	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas
United States	Baptist Memorial Hospital and Cancer Center-Oxford	Oxford	Mississippi
United States	Desert Regional Medical Center	Palm Springs	California
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	Kaiser Permanente - Panorama City	Panorama City	California
United States	The Valley Hospital-Luckow Pavilion	Paramus	New Jersey
United States	Essentia Health - Park Rapids	Park Rapids	Minnesota
United States	Advocate Children's Hospital-Park Ridge	Park Ridge	Illinois
United States	Parker Adventist Hospital	Parker	Colorado
United States	Saint Joseph's Regional Medical Center	Paterson	New Jersey
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois
United States	Sacred Heart Hospital	Pensacola	Florida
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	OSF Saint Francis Radiation Oncology at Peoria Cancer Center	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Valley Radiation Oncology	Peru	Illinois
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Saint Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Cancer Center at Saint Joseph's	Phoenix	Arizona
United States	Phoenix Childrens Hospital	Phoenix	Arizona
United States	FirstHealth of the Carolinas-Moore Regional Hospital	Pinehurst	North Carolina
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Kaiser Permanente Northwest	Portland	Oregon
United States	Legacy Emanuel Children's Hospital	Portland	Oregon
United States	Maine Medical Center-Bramhall Campus	Portland	Maine
United States	Oregon Health and Science University	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Naval Medical Center - Portsmouth	Portsmouth	Virginia
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Geisinger Cancer Services-Pottsville	Pottsville	Pennsylvania
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Utah Valley Regional Medical Center	Provo	Utah
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	Ascension All Saints Hospital	Racine	Wisconsin
United States	Aurora Cancer Care-Racine	Racine	Wisconsin
United States	Corewell Health Reed City Hospital	Reed City	Michigan
United States	Beebe Health Campus	Rehoboth Beach	Delaware
United States	Cancer Care Specialists - Reno	Reno	Nevada
United States	Radiation Oncology Associates	Reno	Nevada
United States	Renown Regional Medical Center	Reno	Nevada
United States	Saint Mary's Regional Medical Center	Reno	Nevada
United States	Valley Medical Center	Renton	Washington
United States	Ascension Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	Vidant Oncology-Richlands	Richlands	North Carolina
United States	Kaiser Permanente-Richmond	Richmond	California
United States	Virginia Cancer Institute	Richmond	Virginia
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Valley Hospital	Ridgewood	New Jersey
United States	Kaiser Permanente-Riverside	Riverside	California
United States	Riverton Hospital	Riverton	Utah
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Penobscot Bay Medical Center	Rockport	Maine
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	Beaumont Children's Hospital-Royal Oak	Royal Oak	Michigan
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	Kaiser Permanente Downtown Commons	Sacramento	California
United States	Kaiser Permanente-South Sacramento	Sacramento	California
United States	Sutter Medical Center Sacramento	Sacramento	California
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Saint George Regional Medical Center	Saint George	Utah
United States	Norris Cotton Cancer Center-North	Saint Johnsbury	Vermont
United States	Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan
United States	Cardinal Glennon Children's Medical Center	Saint Louis	Missouri
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Mercy Hospital South	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Siteman Cancer Center at Christian Hospital	Saint Louis	Missouri
United States	Siteman Cancer Center-South County	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri
United States	Johns Hopkins All Children's Hospital	Saint Petersburg	Florida
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	LDS Hospital	Salt Lake City	Utah
United States	Primary Children's Hospital	Salt Lake City	Utah
United States	Utah Cancer Specialists-Salt Lake City	Salt Lake City	Utah
United States	Children's Hospital of San Antonio	San Antonio	Texas
United States	Methodist Children's Hospital of South Texas	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Kaiser Permanente-San Diego Zion	San Diego	California
United States	Naval Medical Center -San Diego	San Diego	California
United States	Rady Children's Hospital - San Diego	San Diego	California
United States	Kaiser Permanente-San Francisco	San Francisco	California
United States	UCSF Medical Center-Mission Bay	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	Pacific Central Coast Health Center-San Luis Obispo	San Luis Obispo	California
United States	Kaiser Permanente-San Marcos	San Marcos	California
United States	Kaiser San Rafael-Gallinas	San Rafael	California
United States	Essentia Health Sandstone	Sandstone	Minnesota
United States	MaineHealth Cancer Care Center of York County	Sanford	Maine
United States	MaineHealth/SMHC Cancer Care and Blood Disorders-Sanford	Sanford	Maine
United States	Mission Hope Medical Oncology - Santa Maria	Santa Maria	California
United States	Kaiser Permanente-Santa Rosa	Santa Rosa	California
United States	Memorial Health University Medical Center	Savannah	Georgia
United States	Maine Medical Center- Scarborough Campus	Scarborough	Maine
United States	Community Medical Center	Scranton	Pennsylvania
United States	TidalHealth Nanticoke / Allen Cancer Center	Seaford	Delaware
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Seattle Children's Hospital	Seattle	Washington
United States	Swedish Medical Center-Ballard Campus	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	Geisinger Medical Oncology-Selinsgrove	Selinsgrove	Pennsylvania
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin
United States	Henry Ford Macomb Health Center - Shelby Township	Shelby	Michigan
United States	Welch Cancer Center	Sheridan	Wyoming
United States	LSU Health Sciences Center at Shreveport	Shreveport	Louisiana
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Maine Medical Partners - South Portland	South Portland	Maine
United States	Kaiser Permanente-South San Francisco	South San Francisco	California
United States	Ascension Providence Hospitals - Southfield	Southfield	Michigan
United States	Baptist Memorial Hospital and Cancer Center-Desoto	Southhaven	Mississippi
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington
United States	Baystate Medical Center	Springfield	Massachusetts
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Novant Health Cancer Institute - Statesville	Statesville	North Carolina
United States	Ascension Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Marshfield Medical Center-River Region at Stevens Point	Stevens Point	Wisconsin
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Kaiser Permanente-Stockton	Stockton	California
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Saint Vincent Hospital Cancer Center at Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	Aurora Medical Center in Summit	Summit	Wisconsin
United States	Overlook Hospital	Summit	New Jersey
United States	BJC Outpatient Center at Sunset Hills	Sunset Hills	Missouri
United States	Southwest Illinois Health Services LLP	Swansea	Illinois
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	Hematology Oncology Associates of Central New York-Onondaga Hill	Syracuse	New York
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	Madigan Army Medical Center	Tacoma	Washington
United States	Mary Bridge Children's Hospital and Health Center	Tacoma	Washington
United States	Northwest Medical Specialties PLLC	Tacoma	Washington
United States	Moffitt Cancer Center	Tampa	Florida
United States	Moffitt Cancer Center - McKinley Campus	Tampa	Florida
United States	Moffitt Cancer Center-International Plaza	Tampa	Florida
United States	Saint Joseph's Hospital/Children's Hospital-Tampa	Tampa	Florida
United States	Novant Health Cancer Institute - Thomasville	Thomasville	North Carolina
United States	Rocky Mountain Cancer Centers-Thornton	Thornton	Colorado
United States	Mercy Health - Saint Anne Hospital	Toledo	Ohio
United States	ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital	Toledo	Ohio
United States	Saint Vincent Mercy Medical Center	Toledo	Ohio
United States	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio
United States	Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center	Torrance	California
United States	Munson Medical Center	Traverse City	Michigan
United States	William Beaumont Hospital - Troy	Troy	Michigan
United States	Smilow Cancer Hospital Care Center-Trumbull	Trumbull	Connecticut
United States	Banner University Medical Center - Tucson	Tucson	Arizona
United States	University of Arizona Cancer Center-North Campus	Tucson	Arizona
United States	University of Arizona Cancer Center-Orange Grove Campus	Tucson	Arizona
United States	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho
United States	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin
United States	MGC Hematology Oncology-Union	Union	South Carolina
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	Kaiser Permanente Medical Center-Vacaville	Vacaville	California
United States	Kaiser Permanente-Vallejo	Vallejo	California
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Essentia Health Virginia Clinic	Virginia	Minnesota
United States	MD Anderson Cancer Center at Cooper-Voorhees	Voorhees	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington
United States	Kaiser Permanente-Walnut Creek	Walnut Creek	California
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	Children's National Medical Center	Washington	District of Columbia
United States	Illinois CancerCare - Washington	Washington	Illinois
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	Smilow Cancer Hospital Care Center - Waterford	Waterford	Connecticut
United States	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin
United States	Ascension Medical Group Southeast Wisconsin - Mayfair Road	Wauwatosa	Wisconsin
United States	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin
United States	Aurora West Allis Medical Center	West Allis	Wisconsin
United States	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan
United States	University of Cincinnati Cancer Center-West Chester	West Chester	Ohio
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Methodist West Hospital	West Des Moines	Iowa
United States	Saint Mary's Hospital	West Palm Beach	Florida
United States	Reading Hospital	West Reading	Pennsylvania
United States	Saint Ann's Hospital	Westerville	Ohio
United States	UH Seidman Cancer Center at Saint John Medical Center	Westlake	Ohio
United States	Diagnostic and Treatment Center	Weston	Wisconsin
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas
United States	Valley Health System-Hematology/Oncology	Westwood	New Jersey
United States	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado
United States	Presbyterian Intercommunity Hospital	Whittier	California
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Novant Health Cancer Institute - Wilkesboro	Wilkesboro	North Carolina
United States	Wake Forest Baptist Health - Wilkes Medical Center	Wilkesboro	North Carolina
United States	Peninsula Cancer Institute-Williamsburg	Williamsburg	Virginia
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Alfred I duPont Hospital for Children	Wilmington	Delaware
United States	Novant Health Forsyth Medical Center	Winston-Salem	North Carolina
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Kaiser Permanente-Woodland Hills	Woodland Hills	California
United States	University of Michigan Health - West	Wyoming	Michigan
United States	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington
United States	Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus	Ypsilanti	Michigan
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival (PFS)	Will test the null hypothesis (HR=1) for PFS using stratified log-rank test with a one-sided alpha of 0.021. The analysis will be based on modified intent-to-treat and will include all eligible patients as randomized regardless of treatment received. The one-sided alpha of .021 will control of the overall type-one error of the study (including the 2 interim superiority analyses) to be less than .025.	From date of registration to date of first observation of progressive disease according to the 2014 Lugano classification, or death due to any cause, assessed at 2 years
Secondary	Overall survival		2 years
Secondary	Event-free survival (EFS)	Will be estimated using Kaplan-Meier method and compared between treatment arms using cox regression model.	From date of registration to date of first occurrence of EFS event, assessed at 2 years
Secondary	Metabolic complete response rate	Defined using 2014 Lugano classification.	Up to 10 years
Secondary	Incidence of adverse events	Toxicity will be evaluated using Common Terminology Criteria of Adverse Events (CTCAE) version 5 items. Treatment-related toxicities between arms will be compared using Fisher's exact test stratified by age groups. Targeted patient-reported toxicities also will be collected at each time point using the Patient Reported Outcome (PRO)-CTCAE for patients 18 years and older and from youth 12-17 years, using the Pediatric PRO-CTCAE.	Up to 10 years