BLP25 Liposome Vaccine and Bevacizumab After Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Stage IIIA or Stage IIIB Non-Small Cell Lung Cancer That Cannot Be Removed by Surgery

Phase 2

Completed

• Conditions: Lung Cancer
• Interventions: Biological: bevacizumab; Biological: Tecemotide; Drug: carboplatin; Drug: cyclophosphamide; Drug: paclitaxel; Radiation: radiotherapy

• Registration Number: NCT00828009
• Lead Sponsor: ECOG-ACRIN Cancer Research Group

Brief Summary

RATIONALE: Vaccines may help the body build an effective immune response to kill tumor cells. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving vaccine therapy together with bevacizumab after chemotherapy and radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects of giving BLP25 liposome vaccine together with bevacizumab after chemotherapy and radiation therapy in treating patients with newly diagnosed stage IIIA or stage IIIB non-small cell lung cancer that cannot be removed by surgery.

Detailed Description

OBJECTIVES:

Primary

* To determine the safety of BLP25 liposome vaccine (tecemotide) and bevacizumab after definitive chemoradiotherapy and consolidation chemotherapy in patients with newly diagnosed, unresectable stage IIIA or IIIB nonsquamous cell non-small cell lung cancer.

Secondary

* To evaluate the overall survival and progression-free in patients treated with this regimen.

* To evaluate the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study.

Step 1:

* Chemoradiotherapy: Patients receive paclitaxel intravenously (IV) over 1 hour and carboplatin IV over 15-30 minutes once a week for 6 weeks. Patients also undergo concurrent definitive radiotherapy 5 days a week for 6½ weeks. Patients with complete response (CR), partial response (PR), or stable disease (SD) proceed to consolidation chemotherapy.

* Consolidation chemotherapy: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 15-30 minutes on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with CR, PR, or SD proceed to maintenance therapy.

Step 2:

* Maintenance therapy: Patients receive a single dose of cyclophosphamide IV over 15-30 minutes 3 days before the first dose of bevacizumab and BLP25 liposome vaccine. Patients then receive bevacizumab IV over 30-90 minutes on day 1 and BLP25 liposome vaccine subcutaneously on days 1, 8, and 15 of courses 1 and 2 and on day 1 of every other course beginning in course 4. Treatment repeats every 21 days for up to 34 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 5 years.

Study Timeline

• Study First Submitted: 2009-01-22
• Study First Submitted QC: 2009-01-22
• Study First Posted: 2009-01-23
• Study Start: 2011-01-17
• Primary Completion: 2018-08-20
• Results First Submitted: 2019-03-03
• Results First Submitted QC: 2019-03-03
• Results First Posted: 2019-03-26
• Study Completion: 2019-05-22
• Status Verified: 2023-06
• Last Update Submitted: 2023-06-21
• Last Update Posted: 2023-07-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

• Histologically confirmed newly diagnosed nonsquamous non-small cell lung cancer (NSCLC), including the following subtypes:

  • Adenocarcinoma
  • Large cell undifferentiated
  • Bronchoalveolar cell
  • non-small cell carcinoma, not otherwise specified

• Unresectable stage IIIA or stage IIIB disease

  • Patients with stage IIIA disease with mediastinal lymph node enlargement between 1 cm and 2.0 cm on computerized tomography (CT) scan must have these nodes biopsied (pathologic confirmation) to rule out resectability
  • Metastases to contralateral mediastinal or supraclavicular nodes allowed

• Measurable or non-measurable disease, as defined by Response Evaluation Criteria in Solid Tumours (RECIST) criteria

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1

• White blood cell (WBC) ≥ 4,000/mm³ OR Absolute neutrophil count (ANC) ≥ 2,000/mm³

• Platelet count ≥ 140,000/mm³

• Hemoglobin ≥ 9.0 g/dL

• Total bilirubin ≤ 1.5 mg/dL

• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT)+ ≤ 2.5 times upper limit of normal

• Serum creatinine ≤ 1.5 mg/mL OR creatinine clearance ≥ 45 mL/min

• Urine protein:creatinine ratio < 1.0 by urine dipstick OR < 1 g of protein by 24-hour urine collection

• INR ≤ 1.5 OR ≤ 3.0 if patient is on therapeutic anticoagulation

• PTT normal

• Fertile patients must use effective contraception before, during, and for ≥ 6 months after completion of bevacizumab

Step 1

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Exclusion Criteria

• Significant pleural effusion
• CNS metastases by head CT scan or MRI within the past 4 weeks
• Pregnant or breast-feeding
• Prior chemotherapy or monoclonal antibodies for other cancers within 5 years prior to registration
• Prior chemotherapy for lung cancer
• Prior chest radiotherapy
• Ongoing (lasting > 14 days) or active infection or ongoing (lasting > 14 days) fever within the past 6 months
• Gross hemoptysis ≥ grade 2 (defined as ≥ ½ teaspoon of bright red blood per episode) within the past 3 months
• Bleeding ≥ grade 2 or any bleeding requiring intervention
• Clinically significant cardiovascular disease
• Myocardial infarction within the past 6 months
• New York Heart Association class III-IV congestive heart failure
• Unstable angina pectoris
• Serious cardiac arrhythmia requiring medication within the past 4 weeks
• History of hypertensive crisis or hypertensive encephalopathy
• Stroke or transient ischemic attack within the past 6 months
• Peripheral vascular disease ≥ grade 2 within the past 6 months
• Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
• Psychiatric illness or social situation that would limit compliance with study requirements
• History of uncontrolled hypertension (i.e., blood pressure ≥ 150/100 mm Hg) while on stable regimen of antihypertensive therapy
• Significant traumatic injury or serious non-healing wound, ulcer, or bone fracture within the past 4 weeks
• Concurrent major surgical procedure
• Having anticipated major surgical procedure(s) during the course of the study
• Concurrent daily aspirin (> 325 mg/day) or nonsteroidal anti-inflammatory agents (NSAIDs) known to inhibit platelet function
• Recognized immunodeficiency disease, including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia, or hereditary or congenital immunodeficiencies
• Pre-existing medical condition requiring chronic steroids or immunosuppressive therapy
• Autoimmune disease
• Known hepatitis B or C
• Immunotherapy (e.g., interferon, interleukin, sargramostim [GM-CSF], or filgrastim [G-CSF]) within 28 days prior to registration
• Prior splenectomy
• Hypersensitivity to any component of bevacizumab
• Prior core biopsy or any other minor surgical procedure, excluding the placement of a vascular access device, within 7 days prior to registration

Step 2 Inclusion Criteria:

• Serum creatinine ≤ 1.5 mg/ml or calculated creatinine clearance ≥ 45 ml/min
• Urine dipstick must be ≤ 0-1+. If urine dipstick results > 1+, 24 hour urine for protein must be obtained. Patients must have < 1g protein/24 hours to participate in the study
• Patient must be registered to step 2 within 28 days of completion of consolidation chemotherapy
• Patient must have met all eligibility requirements for Step 1
• Platelets ≥ 100,000/mm3

Step 2 Exclusion Criteria:

• Progressive disease or unevaluable disease per RECIST criteria upon post- consolidation chemotherapy evaluation
• Autoimmune disease

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Tecemotide/bevacizumab after chemoradiation	bevacizumab	Concomitant Chemoradiotherapy: Patients (pts) receive paclitaxel intravenously (IV) over 1 hour and carboplatin IV over 15-30 minutes weekly for 6 weeks. Pts also receive radiotherapy 5 days a week for 6½ weeks. Pts with CR, PR, or SD proceed to consolidation chemotherapy. Consolidation chemotherapy: Pts receive paclitaxel IV over 3 hours and carboplatin IV over 15-30 minutes on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease progression (PD) or unacceptable toxicity. Pts with CR, PR, or SD proceed to maintenance therapy. Maintenance therapy: Pts receive a single dose of cyclophosphamide IV over 15-30 minutes 3 days before the first dose of bevacizumab and tecemotide. Pts then receive bevacizumab IV over 30-90 minutes on day 1 and tecemotide subcutaneously on days 1, 8, and 15 of courses 1 and 2 and on day 1 of every other course beginning in course 4. Treatment repeats every 21 days for up to 34 courses in the absence of PD or unacceptable toxicity.
Tecemotide/bevacizumab after chemoradiation	Tecemotide	Concomitant Chemoradiotherapy: Patients (pts) receive paclitaxel intravenously (IV) over 1 hour and carboplatin IV over 15-30 minutes weekly for 6 weeks. Pts also receive radiotherapy 5 days a week for 6½ weeks. Pts with CR, PR, or SD proceed to consolidation chemotherapy. Consolidation chemotherapy: Pts receive paclitaxel IV over 3 hours and carboplatin IV over 15-30 minutes on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease progression (PD) or unacceptable toxicity. Pts with CR, PR, or SD proceed to maintenance therapy. Maintenance therapy: Pts receive a single dose of cyclophosphamide IV over 15-30 minutes 3 days before the first dose of bevacizumab and tecemotide. Pts then receive bevacizumab IV over 30-90 minutes on day 1 and tecemotide subcutaneously on days 1, 8, and 15 of courses 1 and 2 and on day 1 of every other course beginning in course 4. Treatment repeats every 21 days for up to 34 courses in the absence of PD or unacceptable toxicity.
Tecemotide/bevacizumab after chemoradiation	radiotherapy	Concomitant Chemoradiotherapy: Patients (pts) receive paclitaxel intravenously (IV) over 1 hour and carboplatin IV over 15-30 minutes weekly for 6 weeks. Pts also receive radiotherapy 5 days a week for 6½ weeks. Pts with CR, PR, or SD proceed to consolidation chemotherapy. Consolidation chemotherapy: Pts receive paclitaxel IV over 3 hours and carboplatin IV over 15-30 minutes on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease progression (PD) or unacceptable toxicity. Pts with CR, PR, or SD proceed to maintenance therapy. Maintenance therapy: Pts receive a single dose of cyclophosphamide IV over 15-30 minutes 3 days before the first dose of bevacizumab and tecemotide. Pts then receive bevacizumab IV over 30-90 minutes on day 1 and tecemotide subcutaneously on days 1, 8, and 15 of courses 1 and 2 and on day 1 of every other course beginning in course 4. Treatment repeats every 21 days for up to 34 courses in the absence of PD or unacceptable toxicity.
Tecemotide/bevacizumab after chemoradiation	cyclophosphamide	Concomitant Chemoradiotherapy: Patients (pts) receive paclitaxel intravenously (IV) over 1 hour and carboplatin IV over 15-30 minutes weekly for 6 weeks. Pts also receive radiotherapy 5 days a week for 6½ weeks. Pts with CR, PR, or SD proceed to consolidation chemotherapy. Consolidation chemotherapy: Pts receive paclitaxel IV over 3 hours and carboplatin IV over 15-30 minutes on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease progression (PD) or unacceptable toxicity. Pts with CR, PR, or SD proceed to maintenance therapy. Maintenance therapy: Pts receive a single dose of cyclophosphamide IV over 15-30 minutes 3 days before the first dose of bevacizumab and tecemotide. Pts then receive bevacizumab IV over 30-90 minutes on day 1 and tecemotide subcutaneously on days 1, 8, and 15 of courses 1 and 2 and on day 1 of every other course beginning in course 4. Treatment repeats every 21 days for up to 34 courses in the absence of PD or unacceptable toxicity.
Tecemotide/bevacizumab after chemoradiation	carboplatin	Concomitant Chemoradiotherapy: Patients (pts) receive paclitaxel intravenously (IV) over 1 hour and carboplatin IV over 15-30 minutes weekly for 6 weeks. Pts also receive radiotherapy 5 days a week for 6½ weeks. Pts with CR, PR, or SD proceed to consolidation chemotherapy. Consolidation chemotherapy: Pts receive paclitaxel IV over 3 hours and carboplatin IV over 15-30 minutes on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease progression (PD) or unacceptable toxicity. Pts with CR, PR, or SD proceed to maintenance therapy. Maintenance therapy: Pts receive a single dose of cyclophosphamide IV over 15-30 minutes 3 days before the first dose of bevacizumab and tecemotide. Pts then receive bevacizumab IV over 30-90 minutes on day 1 and tecemotide subcutaneously on days 1, 8, and 15 of courses 1 and 2 and on day 1 of every other course beginning in course 4. Treatment repeats every 21 days for up to 34 courses in the absence of PD or unacceptable toxicity.
Tecemotide/bevacizumab after chemoradiation	paclitaxel	Concomitant Chemoradiotherapy: Patients (pts) receive paclitaxel intravenously (IV) over 1 hour and carboplatin IV over 15-30 minutes weekly for 6 weeks. Pts also receive radiotherapy 5 days a week for 6½ weeks. Pts with CR, PR, or SD proceed to consolidation chemotherapy. Consolidation chemotherapy: Pts receive paclitaxel IV over 3 hours and carboplatin IV over 15-30 minutes on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease progression (PD) or unacceptable toxicity. Pts with CR, PR, or SD proceed to maintenance therapy. Maintenance therapy: Pts receive a single dose of cyclophosphamide IV over 15-30 minutes 3 days before the first dose of bevacizumab and tecemotide. Pts then receive bevacizumab IV over 30-90 minutes on day 1 and tecemotide subcutaneously on days 1, 8, and 15 of courses 1 and 2 and on day 1 of every other course beginning in course 4. Treatment repeats every 21 days for up to 34 courses in the absence of PD or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Proportion of Patients With Target Adverse Events for the Step 2 Treatment	Assessed every 3 weeks while on treatment and up to 5 years	The study is to evaluate the safety of the combination of tecemotide immunotherapy with bevacizumab. The target adverse events for the combined treatment are as follows: grade 4-5 hemorrhage, esophagitis, fistula, platelet count decrease (thrombocytopenia), encephalitis infection, or hepatic failure episodes.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	Every 3 months for patients < 2 years from study entry, and every 6 months if patient is 2-5 years from study entry; up to 5 years	Overall survival was defined as the time from the study registration until death from any cause. Patients who were alive or lost to follow-up at the time of analysis were censored at date last known alive.
Progression-free Survival	Every 3 months for patients < 2 years from study entry, and every 6 months if patient is 2-5 years from study entry; up to 5 years	Progression-free survival was defined as the time from study registration to disease progression or death from any cause, whichever came first. If date of death was greater than 3 months after date of last disease assessment that showed progression-free, the patient was censored at the time of last disease assessment. Patients alive and without documented progression were censored at the date last known progression-free.; Progression is defined using Response Evaluation Criteria In Solid Tumors (RECIST) Criteria (version 1.1), as at least 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, the appearance of new lesions, or unequivocal progression of existing non-target lesions.

Trial Locations

Locations (88)

Perry Memorial Hospital; 🇺🇸 Princeton, Illinois, United States

Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center; 🇺🇸 Wilkes-Barre, Pennsylvania, United States

Hematology Oncology Associates - Skokie; 🇺🇸 Skokie, Illinois, United States

Elkhart General Hospital; 🇺🇸 Elkhart, Indiana, United States

West Virginia University Health Sciences Center - Charleston; 🇺🇸 Charleston, West Virginia, United States

Robert H. Lurie Comprehensive Cancer Center at Northwestern University; 🇺🇸 Chicago, Illinois, United States

Hematology and Oncology Associates; 🇺🇸 Chicago, Illinois, United States

Saint Joseph Hospital; 🇺🇸 Chicago, Illinois, United States

Mason District Hospital; 🇺🇸 Havana, Illinois, United States

Tufts Medical Center Cancer Center; 🇺🇸 Boston, Massachusetts, United States

Case Comprehensive Cancer Center; 🇺🇸 Cleveland, Ohio, United States

Waukesha Memorial Hospital Regional Cancer Center; 🇺🇸 Waukesha, Wisconsin, United States

Graham Hospital; 🇺🇸 Canton, Illinois, United States

Vanderbilt-Ingram Cancer Center; 🇺🇸 Nashville, Tennessee, United States

Stanford Cancer Center; 🇺🇸 Stanford, California, United States

Veterans Affairs Medical Center - Palo Alto; 🇺🇸 Palo Alto, California, United States

Medical Center of Central Georgia; 🇺🇸 Macon, Georgia, United States

Memorial Hospital; 🇺🇸 Carthage, Illinois, United States

St. Joseph Medical Center; 🇺🇸 Bloomington, Illinois, United States

Decatur Memorial Hospital Cancer Care Institute; 🇺🇸 Decatur, Illinois, United States

Eureka Community Hospital; 🇺🇸 Eureka, Illinois, United States

Ingalls Cancer Care Center at Ingalls Memorial Hospital; 🇺🇸 Harvey, Illinois, United States

Galesburg Clinic, PC; 🇺🇸 Galesburg, Illinois, United States

Kellogg Cancer Care Center; 🇺🇸 Highland Park, Illinois, United States

Hinsdale Hematology Oncology Associates; 🇺🇸 Hinsdale, Illinois, United States

Provena St. Mary's Regional Cancer Center - Kankakee; 🇺🇸 Kankakee, Illinois, United States

North Shore Oncology and Hematology Associates, Limited - Libertyville; 🇺🇸 Libertyville, Illinois, United States

McDonough District Hospital; 🇺🇸 Macomb, Illinois, United States

Trinity Cancer Center at Trinity Medical Center - 7th Street Campus; 🇺🇸 Moline, Illinois, United States

Cancer Care and Hematology Specialists of Chicagoland - Niles; 🇺🇸 Niles, Illinois, United States

Community Cancer Center; 🇺🇸 Normal, Illinois, United States

BroMenn Regional Medical Center; 🇺🇸 Normal, Illinois, United States

Cancer Treatment Center at Pekin Hospital; 🇺🇸 Pekin, Illinois, United States

Proctor Hospital; 🇺🇸 Peoria, Illinois, United States

Community Hospital of Ottawa; 🇺🇸 Ottawa, Illinois, United States

CCOP - Illinois Oncology Research Association; 🇺🇸 Peoria, Illinois, United States

Oncology Hematology Associates of Central Illinois, PC - Peoria; 🇺🇸 Peoria, Illinois, United States

Methodist Medical Center of Illinois; 🇺🇸 Peoria, Illinois, United States

OSF St. Francis Medical Center; 🇺🇸 Peoria, Illinois, United States

Illinois Valley Community Hospital; 🇺🇸 Peru, Illinois, United States

Swedish-American Regional Cancer Center; 🇺🇸 Rockford, Illinois, United States

Regional Cancer Center at Memorial Medical Center; 🇺🇸 Springfield, Illinois, United States

Center for Cancer Therapy at LaPorte Hospital and Health Services; 🇺🇸 La Porte, Indiana, United States

Howard Community Hospital; 🇺🇸 Kokomo, Indiana, United States

CCOP - Northern Indiana CR Consortium; 🇺🇸 South Bend, Indiana, United States

John Stoddard Cancer Center at Iowa Methodist Medical Center; 🇺🇸 Des Moines, Iowa, United States

McFarland Clinic, PC; 🇺🇸 Ames, Iowa, United States

Saint Joseph Regional Medical Center; 🇺🇸 Mishawaka, Indiana, United States

Memorial Hospital of South Bend; 🇺🇸 South Bend, Indiana, United States

Medical Oncology and Hematology Associates at Mercy Cancer Center; 🇺🇸 Des Moines, Iowa, United States

Medical Oncology and Hematology Associates at John Stoddard Cancer Center; 🇺🇸 Des Moines, Iowa, United States

Cancer Center at Ball Memorial Hospital; 🇺🇸 Muncie, Indiana, United States

CCOP - Iowa Oncology Research Association; 🇺🇸 Des Moines, Iowa, United States

Medical Oncology and Hematology Associates - West Des Moines; 🇺🇸 Clive, Iowa, United States

Mercy Medical Center - Sioux City; 🇺🇸 Sioux City, Iowa, United States

St. Luke's Regional Medical Center; 🇺🇸 Sioux City, Iowa, United States

Mercy Cancer Center at Mercy Medical Center - Des Moines; 🇺🇸 Des Moines, Iowa, United States

Borgess Medical Center; 🇺🇸 Kalamazoo, Michigan, United States

Cancer Resource Center - Lincoln; 🇺🇸 Lincoln, Nebraska, United States

Lakeside Cancer Specialists, PLLC; 🇺🇸 Saint Joseph, Michigan, United States

Bronson Methodist Hospital; 🇺🇸 Kalamazoo, Michigan, United States

CCOP - Missouri Valley Cancer Consortium; 🇺🇸 Omaha, Nebraska, United States

Lakeland Regional Cancer Care Center - St. Joseph; 🇺🇸 Saint Joseph, Michigan, United States

Immanuel Medical Center; 🇺🇸 Omaha, Nebraska, United States

Alegant Health Cancer Center at Bergan Mercy Medical Center; 🇺🇸 Omaha, Nebraska, United States

Creighton University Medical Center; 🇺🇸 Omaha, Nebraska, United States

Lakeside Hospital; 🇺🇸 Omaha, Nebraska, United States

Cancer Institute of New Jersey at Hamilton; 🇺🇸 Hamilton, New Jersey, United States

Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School; 🇺🇸 New Brunswick, New Jersey, United States

Mercy Cancer Center at Mercy Medical Center; 🇺🇸 Canton, Ohio, United States

St. Rita's Medical Center; 🇺🇸 Lima, Ohio, United States

Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest; 🇺🇸 Allentown, Pennsylvania, United States

PinnacleHealth Regional Cancer Center at Polyclinic Hospital; 🇺🇸 Harrisburg, Pennsylvania, United States

Geisinger Cancer Institute at Geisinger Health; 🇺🇸 Danville, Pennsylvania, United States

Geisinger Hazleton Cancer Center; 🇺🇸 Hazleton, Pennsylvania, United States

Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center; 🇺🇸 Hershey, Pennsylvania, United States

Geisinger Medical Group - Scenery Park; 🇺🇸 State College, Pennsylvania, United States

Pottstown Memorial Regional Cancer Center; 🇺🇸 Pottstown, Pennsylvania, United States

Lewistown Hospital; 🇺🇸 Lewistown, Pennsylvania, United States

Mount Nittany Medical Center; 🇺🇸 State College, Pennsylvania, United States

Parkland Memorial Hospital; 🇺🇸 Dallas, Texas, United States

Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas; 🇺🇸 Dallas, Texas, United States

Gundersen Lutheran Center for Cancer and Blood; 🇺🇸 La Crosse, Wisconsin, United States

Regional Cancer Center at Oconomowoc Memorial Hospital; 🇺🇸 Oconomowoc, Wisconsin, United States

West Michigan Cancer Center; 🇺🇸 Kalamazoo, Michigan, United States

Siouxland Hematology-Oncology Associates, LLP; 🇺🇸 Sioux City, Iowa, United States

Stony Brook University Cancer Center; 🇺🇸 Stony Brook, New York, United States

John Stoddard Cancer Center at Iowa Lutheran Hospital; 🇺🇸 Des Moines, Iowa, United States