Testing Continuous Versus Intermittent Treatment With the Study Drug Zanubrutinib for Older Patients With Previously Untreated Mantle Cell Lymphoma
- Conditions
- Mantle Cell Lymphoma
- Interventions
- Other: Patient ObservationProcedure: Bone Marrow BiopsyOther: Fludeoxyglucose F-18Procedure: Positron Emission TomographyProcedure: Computed TomographyProcedure: Magnetic Resonance ImagingProcedure: ColonoscopyProcedure: EsophagogastroduodenoscopyProcedure: Biospecimen CollectionOther: Questionnaire Administration
- Registration Number
- NCT05976763
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- Brief Summary
This phase III trial tests whether continuous or intermittent zanubrutinib after achieving a complete remission (CR) with rituximab works in older adult patients with mantle cell lymphoma (MCL) who have not received treatment in the past (previously untreated). Rituximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Zanubrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. When zanubrutinib is used in MCL, the current standard of care is to continue administering the drug indefinitely until disease progression. This continuous treatment comes with clinical as well as financial toxicity, which could be especially detrimental in older patients. For patients who achieve a CR after initial zanubrutinib plus rituximab therapy, it may be safe and equally effective to stop treatment and restart zanubrutinib upon disease progression rather than continuing indefinitely in previously untreated older adult patients with MCL.
- Detailed Description
PRIMARY OBJECTIVE:
I. To compare time to first progression or death (progression free survival \[PFS\]1) with continuous treatment (Arm A) and time to second progression or death (PFS2) with intermittent treatment that is restarted at first progression (Arm B).
KEY SECONDARY OBJECTIVE:
I. To compare overall survival between patients who achieve a complete remission (CR) with induction therapy subsequently treated with continuous treatment versus (vs.) intermittent treatment as part of maintenance therapy.
SECONDARY OBJECTIVES:
I. To determine overall response rate (ORR) and CR rate to induction therapy with zanubrutinib and rituximab in previously untreated MCL.
II. To determine adverse events during induction and post-induction in each study arm (Arm A and B) by Common Terminology Criteria for Adverse Events (CTCAE) 5.0.
III. To determine PFS1, event free survival (EFS) and overall survival (OS) in each study arm (A and B).
IV. To determine the overall response rate (ORR) and complete response rate (CR) after restarting zanubrutinib, following the first progression, in the intermittent treatment arm (Arm B).
V. To compare burden of symptomatic adverse events (AEs) as assessed by Patient-Reported Outcome Common Terminology Criteria for Adverse Events (PRO-CTCAE) between patients randomized to Arm A versus Arm B.
QUALITY OF LIFE PRIMARY OBJECTIVE:
I. To compare health-related quality of life (QOL) at 12 cycles post-randomization as assessed by the Functional Assessment of Cancer Therapy (FACT) Lymphoma Symptom Index-18 (FLYMSI-18) total score between patients randomized to Arm A versus Arm B.
QUALITY OF LIFE SECONDARY OBJECTIVES:
I. To compare health-related QOL at other time points as assessed by the FLYMSI-18 total score between patients randomized to Arm A versus Arm B.
II. To compare burden of symptomatic AEs as assessed by PRO-CTCAE between patients randomized to continuous (Arm A) versus intermittent (Arm B) zanubrutinib treatment.
QUALITY OF LIFE EXPLORATORY OBJECTIVES:
I. To compare the geriatric functional and cognitive PRO as assessed by Elderly Functional Index (EFLI) and Neurology (Neuro) QOL in Arm A versus Arm B.
II. To compare cognitive function at various time points as assessed by the Neuro-QOL between patients randomized to continuous (Arm A) versus intermittent (Arm B) zanubrutinib treatment.
EXPLORATORY OBJECTIVES:
I. To evaluate the completion rate of a lymphoma-specific patient assessment of life survey (PALS) with patient directed questions on life, health, and social determinants of health (SDH) and assess the impact of the survey collected data on outcomes for all enrolled patients (study arms A and B).
II. To evaluate minimal residual disease (MRD) in those patients who achieve a CR after induction therapy (arms A and B) and how detectable MRD status changes after continued therapy vs. discontinuation of therapy (i.e. arms A vs. B).
OUTLINE:
INDUCTION THERAPY: Patients receive zanubrutinib orally (PO) and rituximab intravenously (IV) on study. Patients undergo bone marrow biopsy and fluciclovine F18 (FDG) positron emission tomography (PET)/ computed tomography (CT) or CT throughout the trial. Patients may also undergo esophagogastroduodenoscopy (EGD) and/or colonoscopy on study as clinically indicated. Patients may optionally undergo blood sample collection throughout the trial.
MAINTENANCE THERAPY: Patients achieving a CR after induction therapy are randomized to 1 of 2 arms.
ARM A: Patients receive zanubrutinib PO until first disease progression on study. Patients undergo CT or magnetic resonance imaging (MRI) or FDG PET/CT throughout the trial. Patients may optionally undergo blood sample collection throughout the trial.
ARM B: Patients undergo observation until first disease progression and then receive zanubrutinib PO until second disease progression on study. Patients undergo CT or MRI or FDG PET/CT throughout the trial. Patients may optionally undergo blood sample collection throughout the trial.
After completion of study treatment, patients are followed within 30 days and every 6 months for 10 years.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 421
-
• Histologically confirmed mantle cell lymphoma with cyclin D1 (BCL1) expression by immunohistochemical stains and/or t(11;14) by cytogenetics or fluorescence in situ hybridization (FISH) as confirmed by the enrolling center
-
Any stage allowed (stage I-IV)
- Presence of measurable disease, defined as >= 1 nodal lesion that is > 1.5 cm in longest diameter or >= 1 extranodal lesion that is > 1 cm in longest diameter
- Steroids for management of mantle cell lymphoma are allowed up to a dose of prednisone 100mg/day (or equivalent) for up to 7 days
- No prior systemic treatment for mantle cell lymphoma
- No prior radiation treatment for stage I MCL
- No prior exposure to a BTK inhibitor or anti-CD20 monoclonal antibody
- No prior stem cell transplant
- Age >= 70 years OR age >= 60 to < 70 years with comorbidities precluding autologous stem cell transplantation (autoSCT) including at least one of the following: a) cardiac ejection fraction (EF) < 45%, b) diffusing capacity for carbon monoxide < 60% predicted; c) creatinine clearance < 70 but > 30ml/minute (min); d) Eastern Cooperative Oncology Group (ECOG) performance status of 2, which poses an unacceptable risk of toxicity for high-dose therapy and stem cell transplantation; or e) Cumulative Illness Rating Scales (CIRS) total score > 6
- ECOG Performance Status 0-2
- Absolute neutrophil count (ANC) >= 750/mm^3 (without growth factor support within 7 days)
- Platelet count >= 75,000/mm^3 (or >= 50,000/mm^3 for patients with bone marrow involvement of lymphoma) without growth factor support or transfusion within 7 days
- Creatinine clearance >= 30 mL/ min determined by either: a) Estimation using the Cockcroft-Gault equation or b) Measurement by nuclear medicine scan or 24 hour urine collection
- Total bilirubin =< 1.5 x upper limit of normal (ULN) (unless documented Gilbert's syndrome)
- Aspartate transferase (AST) / alanine transaminase (ALT) =< 3 x ULN
- Patients should not be considered candidates for stem cell transplant or must have declined a stem cell transplant strategy
- No clinically significant cardiovascular disease including the following
-
Unstable angina within 3 months before registration
-
New York Heart Association class III or IV congestive heart failure
-
History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes)
-
QT correction formula (QTcF) > 480 msecs based on Fredericia's formula
-
History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
- No active Hepatitis B or Hepatitis C infection. Patients with prior hepatitis B virus (HBV) exposure (positive HBV core antibody and/or surface antigen) are eligible if they have no detectable viral load, and are taking appropriate prophylactic antiviral therapy to prevent reactivation. Patients with history of hepatitis C virus (HCV) are eligible if they have an undetectable HCV viral load
- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
- No history of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention
- No history of stroke or intracranial hemorrhage within 6 months prior to registration
- No disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction. Patient must be able to swallow pills
- Potential trial participants should have recovered from major surgery
- No vaccination with a live vaccine within 35 days prior to registration
- No hypersensitivity to zanubrutinib or rituximab or any of the other ingredients of the study drugs
- Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study.
- Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment
- Avoid use of moderate CYP3A4 inhibitors, PGP inhibitors, and moderate CYP3A4 inducers
- Archival tissue must be available for submission in all patients for histopathology review, though participation in correlative substudies is optional
-
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Induction therapy (Zanubrutinib, rituximab) Rituximab Patients receive zanubrutinib PO and rituximab IV on study. Patients undergo bone marrow biopsy and FDG PET/CT or CT throughout the trial. Patients may also undergo EDG and/or colonoscopy on study as clinically indicated. Patients may optionally undergo blood sample collection throughout the trial. Arm A (Zanubrutinib) Colonoscopy Patients receive zanubrutinib PO until first disease progression on study. Patients undergo CT or MRI or FDG PET/CT throughout the trial. Patients may optionally undergo blood sample collection throughout the trial. Induction therapy (Zanubrutinib, rituximab) Patient Observation Patients receive zanubrutinib PO and rituximab IV on study. Patients undergo bone marrow biopsy and FDG PET/CT or CT throughout the trial. Patients may also undergo EDG and/or colonoscopy on study as clinically indicated. Patients may optionally undergo blood sample collection throughout the trial. Induction therapy (Zanubrutinib, rituximab) Bone Marrow Biopsy Patients receive zanubrutinib PO and rituximab IV on study. Patients undergo bone marrow biopsy and FDG PET/CT or CT throughout the trial. Patients may also undergo EDG and/or colonoscopy on study as clinically indicated. Patients may optionally undergo blood sample collection throughout the trial. Induction therapy (Zanubrutinib, rituximab) Fludeoxyglucose F-18 Patients receive zanubrutinib PO and rituximab IV on study. Patients undergo bone marrow biopsy and FDG PET/CT or CT throughout the trial. Patients may also undergo EDG and/or colonoscopy on study as clinically indicated. Patients may optionally undergo blood sample collection throughout the trial. Induction therapy (Zanubrutinib, rituximab) Positron Emission Tomography Patients receive zanubrutinib PO and rituximab IV on study. Patients undergo bone marrow biopsy and FDG PET/CT or CT throughout the trial. Patients may also undergo EDG and/or colonoscopy on study as clinically indicated. Patients may optionally undergo blood sample collection throughout the trial. Induction therapy (Zanubrutinib, rituximab) Computed Tomography Patients receive zanubrutinib PO and rituximab IV on study. Patients undergo bone marrow biopsy and FDG PET/CT or CT throughout the trial. Patients may also undergo EDG and/or colonoscopy on study as clinically indicated. Patients may optionally undergo blood sample collection throughout the trial. Induction therapy (Zanubrutinib, rituximab) Magnetic Resonance Imaging Patients receive zanubrutinib PO and rituximab IV on study. Patients undergo bone marrow biopsy and FDG PET/CT or CT throughout the trial. Patients may also undergo EDG and/or colonoscopy on study as clinically indicated. Patients may optionally undergo blood sample collection throughout the trial. Induction therapy (Zanubrutinib, rituximab) Esophagogastroduodenoscopy Patients receive zanubrutinib PO and rituximab IV on study. Patients undergo bone marrow biopsy and FDG PET/CT or CT throughout the trial. Patients may also undergo EDG and/or colonoscopy on study as clinically indicated. Patients may optionally undergo blood sample collection throughout the trial. Arm A (Zanubrutinib) Esophagogastroduodenoscopy Patients receive zanubrutinib PO until first disease progression on study. Patients undergo CT or MRI or FDG PET/CT throughout the trial. Patients may optionally undergo blood sample collection throughout the trial. Induction therapy (Zanubrutinib, rituximab) Colonoscopy Patients receive zanubrutinib PO and rituximab IV on study. Patients undergo bone marrow biopsy and FDG PET/CT or CT throughout the trial. Patients may also undergo EDG and/or colonoscopy on study as clinically indicated. Patients may optionally undergo blood sample collection throughout the trial. Induction therapy (Zanubrutinib, rituximab) Biospecimen Collection Patients receive zanubrutinib PO and rituximab IV on study. Patients undergo bone marrow biopsy and FDG PET/CT or CT throughout the trial. Patients may also undergo EDG and/or colonoscopy on study as clinically indicated. Patients may optionally undergo blood sample collection throughout the trial. Induction therapy (Zanubrutinib, rituximab) Questionnaire Administration Patients receive zanubrutinib PO and rituximab IV on study. Patients undergo bone marrow biopsy and FDG PET/CT or CT throughout the trial. Patients may also undergo EDG and/or colonoscopy on study as clinically indicated. Patients may optionally undergo blood sample collection throughout the trial. Arm A (Zanubrutinib) Patient Observation Patients receive zanubrutinib PO until first disease progression on study. Patients undergo CT or MRI or FDG PET/CT throughout the trial. Patients may optionally undergo blood sample collection throughout the trial. Arm A (Zanubrutinib) Bone Marrow Biopsy Patients receive zanubrutinib PO until first disease progression on study. Patients undergo CT or MRI or FDG PET/CT throughout the trial. Patients may optionally undergo blood sample collection throughout the trial. Arm A (Zanubrutinib) Fludeoxyglucose F-18 Patients receive zanubrutinib PO until first disease progression on study. Patients undergo CT or MRI or FDG PET/CT throughout the trial. Patients may optionally undergo blood sample collection throughout the trial. Arm A (Zanubrutinib) Positron Emission Tomography Patients receive zanubrutinib PO until first disease progression on study. Patients undergo CT or MRI or FDG PET/CT throughout the trial. Patients may optionally undergo blood sample collection throughout the trial. Arm A (Zanubrutinib) Computed Tomography Patients receive zanubrutinib PO until first disease progression on study. Patients undergo CT or MRI or FDG PET/CT throughout the trial. Patients may optionally undergo blood sample collection throughout the trial. Arm A (Zanubrutinib) Magnetic Resonance Imaging Patients receive zanubrutinib PO until first disease progression on study. Patients undergo CT or MRI or FDG PET/CT throughout the trial. Patients may optionally undergo blood sample collection throughout the trial. Arm A (Zanubrutinib) Biospecimen Collection Patients receive zanubrutinib PO until first disease progression on study. Patients undergo CT or MRI or FDG PET/CT throughout the trial. Patients may optionally undergo blood sample collection throughout the trial. Arm A (Zanubrutinib) Questionnaire Administration Patients receive zanubrutinib PO until first disease progression on study. Patients undergo CT or MRI or FDG PET/CT throughout the trial. Patients may optionally undergo blood sample collection throughout the trial. ARM B (Observation) Patient Observation Patients undergo observation until first disease progression and then receive zanubrutinib PO until second disease progression on study. Patients undergo CT or MRI or FDG PET/CT throughout the trial. Patients may optionally undergo blood sample collection throughout the trial. ARM B (Observation) Bone Marrow Biopsy Patients undergo observation until first disease progression and then receive zanubrutinib PO until second disease progression on study. Patients undergo CT or MRI or FDG PET/CT throughout the trial. Patients may optionally undergo blood sample collection throughout the trial. ARM B (Observation) Fludeoxyglucose F-18 Patients undergo observation until first disease progression and then receive zanubrutinib PO until second disease progression on study. Patients undergo CT or MRI or FDG PET/CT throughout the trial. Patients may optionally undergo blood sample collection throughout the trial. ARM B (Observation) Positron Emission Tomography Patients undergo observation until first disease progression and then receive zanubrutinib PO until second disease progression on study. Patients undergo CT or MRI or FDG PET/CT throughout the trial. Patients may optionally undergo blood sample collection throughout the trial. ARM B (Observation) Computed Tomography Patients undergo observation until first disease progression and then receive zanubrutinib PO until second disease progression on study. Patients undergo CT or MRI or FDG PET/CT throughout the trial. Patients may optionally undergo blood sample collection throughout the trial. ARM B (Observation) Magnetic Resonance Imaging Patients undergo observation until first disease progression and then receive zanubrutinib PO until second disease progression on study. Patients undergo CT or MRI or FDG PET/CT throughout the trial. Patients may optionally undergo blood sample collection throughout the trial. ARM B (Observation) Esophagogastroduodenoscopy Patients undergo observation until first disease progression and then receive zanubrutinib PO until second disease progression on study. Patients undergo CT or MRI or FDG PET/CT throughout the trial. Patients may optionally undergo blood sample collection throughout the trial. ARM B (Observation) Colonoscopy Patients undergo observation until first disease progression and then receive zanubrutinib PO until second disease progression on study. Patients undergo CT or MRI or FDG PET/CT throughout the trial. Patients may optionally undergo blood sample collection throughout the trial. ARM B (Observation) Biospecimen Collection Patients undergo observation until first disease progression and then receive zanubrutinib PO until second disease progression on study. Patients undergo CT or MRI or FDG PET/CT throughout the trial. Patients may optionally undergo blood sample collection throughout the trial. ARM B (Observation) Questionnaire Administration Patients undergo observation until first disease progression and then receive zanubrutinib PO until second disease progression on study. Patients undergo CT or MRI or FDG PET/CT throughout the trial. Patients may optionally undergo blood sample collection throughout the trial. Induction therapy (Zanubrutinib, rituximab) Zanubrutinib Patients receive zanubrutinib PO and rituximab IV on study. Patients undergo bone marrow biopsy and FDG PET/CT or CT throughout the trial. Patients may also undergo EDG and/or colonoscopy on study as clinically indicated. Patients may optionally undergo blood sample collection throughout the trial. Arm A (Zanubrutinib) Zanubrutinib Patients receive zanubrutinib PO until first disease progression on study. Patients undergo CT or MRI or FDG PET/CT throughout the trial. Patients may optionally undergo blood sample collection throughout the trial. ARM B (Observation) Zanubrutinib Patients undergo observation until first disease progression and then receive zanubrutinib PO until second disease progression on study. Patients undergo CT or MRI or FDG PET/CT throughout the trial. Patients may optionally undergo blood sample collection throughout the trial.
- Primary Outcome Measures
Name Time Method Progression-free survival (PFS) 1 (Arm A) Time from randomization until the earlier of first progression or death from any cause, assessed up to 10 years Hazard ratios on the treatment effect will be estimated using a stratified cox proportional hazards model, stratified on age and mantle cell lymphoma (MCL) International Prognostic Index (IPI) score. The primary analysis for non-inferiority will be based on an intent-to-treat (ITT) analysis and will include all randomized patients in the analyses, regardless of eligibility or treatment status. Sensitivity analyses will also be done in an ancillary manner to evaluate and compare our endpoints using a modified ITT approach, and exclude from the analysis those classified as ineligible as well as those who withdraw right after randomization prior to any treatment/observation monitoring.
Progression-free survival (PFS) 2 (Arm B) Time from randomization until the earlier of second progression or death from any cause, assessed up to 10 years Hazard ratios on the treatment effect will be estimated using a stratified cox proportional hazards model, stratified on age and MCL IPI score. The primary analysis for non-inferiority will be based on an ITT analysis and will include all randomized patients in the analyses, regardless of eligibility or treatment status. Sensitivity analyses will also be done in an ancillary manner to evaluate and compare our endpoints using a modified ITT approach, and exclude from the analysis those classified as ineligible as well as those who withdraw right after randomization prior to any treatment/observation monitoring.
- Secondary Outcome Measures
Name Time Method Overall survival (OS) (Arms A and B) Time from randomization until death from any cause, assessed up to 10 years Kaplan-Meier methodology will be used to estimate the distributions of OS by treatment arm and log-rank test statistics will be used to compare these distributions between the two treatment arms. Cox Proportional Hazards models may be used to further evaluate covariates of interest with OS, including assessment of treatment effects when adjusting for other known risk factors in the model.
Incidence of adverse events Up to 10 years Will be evaluated and captured using the CTCAE 5.0, where the type and severity grade of each adverse event will be collected and tabulated within each of the treatment arms. Perceived attribution to study treatment will also be captured.
The analysis population for this secondary endpoint will include all patients who are registered and randomized on the study and receive at least one dose of study treatment. Adverse events will be monitored continuously throughout the course of the study as well as analyzed at the time of the final primary endpoint analysis.
Summary statistics and frequency tables will be used to describe the distributions of adverse events. Rates of adverse events occurring in compared across the treatment arms with chi-squared tests Tolerability will also be evaluated, summarizing rates of dose delays or modifications, reasons patients end treatment, and time to end of active treatment.Overall response rate (ORR, complete + partial remission) up to 10 years Will be assessed using Lugano criteria. ORR to induction is defined as the number of patients with complete or partial remission at the end of induction divided by the number of patients who receive at least one dose of the induction regimen. ORR to restart of zanubrutinib is only defined for Arm B, as the number of patients with complete or partial remission after restart of zanubrutinib divided by the number of patients that restart zanubrutinib after first disease progression following randomization. The frequencies and rates of tumor response categories will be summarized by treatment arm for response to induction as well as response to restart of zanubrutinib (Arm B only). ORR to induction and ORR to restart of zanubrutinib (Arm B only) with 95% exact binomial confidence intervals will be calculated by treatment arm. To compare the association of treatment arm and ORR to induction, chi-squared or Fisher's Exact test will be used, whichever is more appropriate at final analysis.
Complete response rate (CR) Up to 10 years Will be assessed using Lugano criteria. CR to induction is defined as the number of patients with complete remission at the end of induction divided by the number of eligible patients who receive at least one dose of the induction regimen. CR to restart of zanubrutinib is only defined for Arm B, as the number of patients with complete remission after restart of zanubrutinib divided by the number of eligible patients that restart zanubrutinib after first disease progression following randomization. CR to induction and CR to restart of zanubrutinib (Arm B patients only) with 95% exact binomial confidence intervals will be calculated by treatment arm. To compare the association of treatment arm and CR to induction, chi-squared or Fisher's Exact test will be used, whichever is more appropriate at the time of the final analysis.
Event-free survival (EFS) 1 Time from randomization (Arms A and B) until the earlier of first progression, start of an alternative MCL therapy, or death from any cause, assessed up to 10 years. For EFS1, patients without an event will be censored at the last known clinical assessment. Any patient who goes to transplant will be censored at the last known clinical assessment prior to transplant. Kaplan-Meier methodology will be used to estimate the distribution of EFS. Cox Proportional Hazards models may be used to further evaluate covariates of interest with EFS.
Event-free survival (EFS) 2 Time from randomization (Arm B) until the earlier of second progression, start of an alternative MCL therapy, or death from any cause, assessed up to 10 years. For EFS2, patients without an event will be censored at the last known clinical assessment. Any patient who goes to transplant will be censored at the last known clinical assessment prior to transplant. Kaplan-Meier methodology will be used to estimate the distribution of EFS. Cox Proportional Hazards models may be used to further evaluate covariates of interest with EFS.
Trial Locations
- Locations (209)
Tower Cancer Research Foundation
🇺🇸Beverly Hills, California, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
City of Hope at Irvine Lennar
🇺🇸Irvine, California, United States
Cedars Sinai Medical Center
🇺🇸Los Angeles, California, United States
Smilow Cancer Hospital-Derby Care Center
🇺🇸Derby, Connecticut, United States
Smilow Cancer Hospital Care Center-Fairfield
🇺🇸Fairfield, Connecticut, United States
Smilow Cancer Hospital Care Center at Glastonbury
🇺🇸Glastonbury, Connecticut, United States
Smilow Cancer Hospital Care Center at Greenwich
🇺🇸Greenwich, Connecticut, United States
Smilow Cancer Hospital Care Center - Guilford
🇺🇸Guilford, Connecticut, United States
Smilow Cancer Hospital Care Center at Saint Francis
🇺🇸Hartford, Connecticut, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Yale-New Haven Hospital North Haven Medical Center
🇺🇸North Haven, Connecticut, United States
Smilow Cancer Hospital Care Center at Long Ridge
🇺🇸Stamford, Connecticut, United States
Smilow Cancer Hospital-Torrington Care Center
🇺🇸Torrington, Connecticut, United States
Smilow Cancer Hospital Care Center-Trumbull
🇺🇸Trumbull, Connecticut, United States
Smilow Cancer Hospital-Waterbury Care Center
🇺🇸Waterbury, Connecticut, United States
Smilow Cancer Hospital Care Center - Waterford
🇺🇸Waterford, Connecticut, United States
Helen F Graham Cancer Center
🇺🇸Newark, Delaware, United States
Medical Oncology Hematology Consultants PA
🇺🇸Newark, Delaware, United States
Grady Health System
🇺🇸Atlanta, Georgia, United States
Emory University Hospital Midtown
🇺🇸Atlanta, Georgia, United States
Emory University Hospital/Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Emory Saint Joseph's Hospital
🇺🇸Atlanta, Georgia, United States
Augusta University Medical Center
🇺🇸Augusta, Georgia, United States
Emory Johns Creek Hospital
🇺🇸Johns Creek, Georgia, United States
Saint Alphonsus Cancer Care Center-Boise
🇺🇸Boise, Idaho, United States
Saint Luke's Cancer Institute - Boise
🇺🇸Boise, Idaho, United States
Saint Alphonsus Cancer Care Center-Caldwell
🇺🇸Caldwell, Idaho, United States
Kootenai Health - Coeur d'Alene
🇺🇸Coeur d'Alene, Idaho, United States
Saint Luke's Cancer Institute - Fruitland
🇺🇸Fruitland, Idaho, United States
Saint Luke's Cancer Institute - Meridian
🇺🇸Meridian, Idaho, United States
Saint Alphonsus Cancer Care Center-Nampa
🇺🇸Nampa, Idaho, United States
Saint Luke's Cancer Institute - Nampa
🇺🇸Nampa, Idaho, United States
Kootenai Clinic Cancer Services - Post Falls
🇺🇸Post Falls, Idaho, United States
Kootenai Clinic Cancer Services - Sandpoint
🇺🇸Sandpoint, Idaho, United States
Illinois CancerCare-Bloomington
🇺🇸Bloomington, Illinois, United States
Illinois CancerCare-Canton
🇺🇸Canton, Illinois, United States
Illinois CancerCare-Carthage
🇺🇸Carthage, Illinois, United States
Chelsea Hospital
🇺🇸Chelsea, Michigan, United States
University of Illinois
🇺🇸Chicago, Illinois, United States
Carle at The Riverfront
🇺🇸Danville, Illinois, United States
Cancer Care Specialists of Illinois - Decatur
🇺🇸Decatur, Illinois, United States
Decatur Memorial Hospital
🇺🇸Decatur, Illinois, United States
Illinois CancerCare-Dixon
🇺🇸Dixon, Illinois, United States
Carle Physician Group-Effingham
🇺🇸Effingham, Illinois, United States
Crossroads Cancer Center
🇺🇸Effingham, Illinois, United States
Illinois CancerCare-Eureka
🇺🇸Eureka, Illinois, United States
Illinois CancerCare-Galesburg
🇺🇸Galesburg, Illinois, United States
Illinois CancerCare-Kewanee Clinic
🇺🇸Kewanee, Illinois, United States
Illinois CancerCare-Macomb
🇺🇸Macomb, Illinois, United States
Carle Physician Group-Mattoon/Charleston
🇺🇸Mattoon, Illinois, United States
Cancer Care Center of O'Fallon
🇺🇸O'Fallon, Illinois, United States
Illinois CancerCare-Ottawa Clinic
🇺🇸Ottawa, Illinois, United States
Illinois CancerCare-Princeton
🇺🇸Princeton, Illinois, United States
Illinois CancerCare - Washington
🇺🇸Washington, Illinois, United States
Northwest Cancer Center - Main Campus
🇺🇸Crown Point, Indiana, United States
Illinois CancerCare-Pekin
🇺🇸Pekin, Illinois, United States
Illinois CancerCare-Peoria
🇺🇸Peoria, Illinois, United States
Carle Cancer Center
🇺🇸Urbana, Illinois, United States
Illinois CancerCare-Peru
🇺🇸Peru, Illinois, United States
Northwest Oncology LLC
🇺🇸Dyer, Indiana, United States
Saint Mary Medical Center
🇺🇸Hobart, Indiana, United States
Memorial Hospital East
🇺🇸Shiloh, Illinois, United States
Southern Illinois University School of Medicine
🇺🇸Springfield, Illinois, United States
Springfield Clinic
🇺🇸Springfield, Illinois, United States
Springfield Memorial Hospital
🇺🇸Springfield, Illinois, United States
Northwest Cancer Center - Hobart
🇺🇸Hobart, Indiana, United States
Saint Catherine Hospital
🇺🇸Indianapolis, Indiana, United States
The Community Hospital
🇺🇸Munster, Indiana, United States
Women's Diagnostic Center - Munster
🇺🇸Munster, Indiana, United States
Northwest Cancer Center - Valparaiso
🇺🇸Valparaiso, Indiana, United States
Mary Greeley Medical Center
🇺🇸Ames, Iowa, United States
McFarland Clinic - Ames
🇺🇸Ames, Iowa, United States
UI Health Care Mission Cancer and Blood - Ankeny Clinic
🇺🇸Ankeny, Iowa, United States
McFarland Clinic - Boone
🇺🇸Boone, Iowa, United States
Saint Anthony Regional Hospital
🇺🇸Carroll, Iowa, United States
Iowa Methodist Medical Center
🇺🇸Des Moines, Iowa, United States
UI Health Care Mission Cancer and Blood - Des Moines Clinic
🇺🇸Des Moines, Iowa, United States
Broadlawns Medical Center
🇺🇸Des Moines, Iowa, United States
Lawrence Memorial Hospital
🇺🇸Lawrence, Kansas, United States
Mercy Medical Center - Des Moines
🇺🇸Des Moines, Iowa, United States
McFarland Clinic - Trinity Cancer Center
🇺🇸Fort Dodge, Iowa, United States
Trinity Regional Medical Center
🇺🇸Fort Dodge, Iowa, United States
University of Iowa/Holden Comprehensive Cancer Center
🇺🇸Iowa City, Iowa, United States
The University of Kansas Cancer Center - Olathe
🇺🇸Olathe, Kansas, United States
McFarland Clinic - Jefferson
🇺🇸Jefferson, Iowa, United States
McFarland Clinic - Marshalltown
🇺🇸Marshalltown, Iowa, United States
HaysMed
🇺🇸Hays, Kansas, United States
University of Kansas Cancer Center
🇺🇸Kansas City, Kansas, United States
University of Kansas Cancer Center-Overland Park
🇺🇸Overland Park, Kansas, United States
Freeman Physician Group of Pittsburg
🇺🇸Pittsburg, Kansas, United States
Salina Regional Health Center
🇺🇸Salina, Kansas, United States
University of Kansas Health System Saint Francis Campus
🇺🇸Topeka, Kansas, United States
University of Kansas Hospital-Westwood Cancer Center
🇺🇸Westwood, Kansas, United States
Alliance for Clinical Trials in Oncology
🇺🇸Boston, Massachusetts, United States
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
🇺🇸Ann Arbor, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology - Brighton
🇺🇸Brighton, Michigan, United States
Trinity Health Medical Center - Brighton
🇺🇸Brighton, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology - Canton
🇺🇸Canton, Michigan, United States
Trinity Health Medical Center - Canton
🇺🇸Canton, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
🇺🇸Chelsea, Michigan, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Weisberg Cancer Treatment Center
🇺🇸Farmington Hills, Michigan, United States
Corewell Health Farmington Hills Hospital
🇺🇸Farmington Hills, Michigan, United States
Cancer Hematology Centers - Flint
🇺🇸Flint, Michigan, United States
Genesee Hematology Oncology PC
🇺🇸Flint, Michigan, United States
Genesys Hurley Cancer Institute
🇺🇸Flint, Michigan, United States
Hurley Medical Center
🇺🇸Flint, Michigan, United States
Trinity Health Saint Mary Mercy Livonia Hospital
🇺🇸Livonia, Michigan, United States
Henry Ford Saint John Hospital - Macomb Medical
🇺🇸Macomb, Michigan, United States
Corewell Health William Beaumont University Hospital
🇺🇸Royal Oak, Michigan, United States
MyMichigan Medical Center Saginaw
🇺🇸Saginaw, Michigan, United States
Oncology Hematology Associates of Saginaw Valley PC
🇺🇸Saginaw, Michigan, United States
MyMichigan Medical Center Tawas
🇺🇸Tawas City, Michigan, United States
Corewell Health Beaumont Troy Hospital
🇺🇸Troy, Michigan, United States
Saint Mary's Oncology/Hematology Associates of West Branch
🇺🇸West Branch, Michigan, United States
Huron Gastroenterology PC
🇺🇸Ypsilanti, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
🇺🇸Ypsilanti, Michigan, United States
Sanford Joe Lueken Cancer Center
🇺🇸Bemidji, Minnesota, United States
Essentia Health Saint Joseph's Medical Center
🇺🇸Brainerd, Minnesota, United States
Mercy Hospital
🇺🇸Coon Rapids, Minnesota, United States
Essentia Health - Deer River Clinic
🇺🇸Deer River, Minnesota, United States
Essentia Health Cancer Center
🇺🇸Duluth, Minnesota, United States
Essentia Health Hibbing Clinic
🇺🇸Hibbing, Minnesota, United States
Saint John's Hospital - Healtheast
🇺🇸Maplewood, Minnesota, United States
Abbott-Northwestern Hospital
🇺🇸Minneapolis, Minnesota, 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
Essentia Health Sandstone
🇺🇸Sandstone, Minnesota, United States
Essentia Health Virginia Clinic
🇺🇸Virginia, Minnesota, United States
Saint Francis Medical Center
🇺🇸Cape Girardeau, Missouri, United States
Saint Luke's Hospital
🇺🇸Chesterfield, Missouri, United States
Siteman Cancer Center at West County Hospital
🇺🇸Creve Coeur, Missouri, United States
University Health Truman Medical Center
🇺🇸Kansas City, Missouri, United States
University of Kansas Cancer Center - North
🇺🇸Kansas City, Missouri, United States
University of Kansas Cancer Center - Lee's Summit
🇺🇸Lee's Summit, Missouri, United States
University of Kansas Cancer Center at North Kansas City Hospital
🇺🇸North Kansas City, Missouri, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Mercy Hospital Springfield
🇺🇸Springfield, Missouri, United States
Benefis Sletten Cancer Institute
🇺🇸Great Falls, Montana, United States
Mercy Hospital South
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center-South County
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center at Saint Peters Hospital
🇺🇸Saint Peters, Missouri, United States
Siteman Cancer Center at Christian Hospital
🇺🇸Saint Louis, Missouri, United States
CoxHealth South Hospital
🇺🇸Springfield, Missouri, United States
Community Medical Center
🇺🇸Missoula, Montana, United States
Nebraska Medicine-Bellevue
🇺🇸Bellevue, Nebraska, United States
Community Hospital of Anaconda
🇺🇸Anaconda, Montana, United States
Bozeman Health Deaconess Hospital
🇺🇸Bozeman, Montana, United States
Logan Health Medical Center
🇺🇸Kalispell, Montana, United States
Billings Clinic Cancer Center
🇺🇸Billings, Montana, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Hematology Oncology Associates of CNY at Camillus
🇺🇸Camillus, New York, United States
Hematology Oncology Associates of Central New York-East Syracuse
🇺🇸East Syracuse, New York, United States
NYP/Weill Cornell Medical Center
🇺🇸New York, New York, United States
University of Rochester
🇺🇸Rochester, New York, United States
Wilmot Cancer Institute at Webster
🇺🇸Webster, New York, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸Chapel Hill, North Carolina, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Nebraska Medicine-Village Pointe
🇺🇸Omaha, Nebraska, United States
Sanford Bismarck Medical Center
🇺🇸Bismarck, North Dakota, 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
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Cancer Centers of Southwest Oklahoma Research
🇺🇸Lawton, Oklahoma, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Oklahoma Cancer Specialists and Research Institute-Tulsa
🇺🇸Tulsa, Oklahoma, United States
Providence Newberg Medical Center
🇺🇸Newberg, Oregon, United States
Saint Alphonsus Cancer Care Center-Ontario
🇺🇸Ontario, Oregon, United States
Providence Willamette Falls Medical Center
🇺🇸Oregon City, Oregon, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Providence Saint Vincent Medical Center
🇺🇸Portland, Oregon, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States
Smilow Cancer Hospital Care Center - Westerly
🇺🇸Westerly, Rhode Island, United States
Prisma Health Cancer Institute - Spartanburg
🇺🇸Boiling Springs, South Carolina, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Prisma Health Cancer Institute - Easley
🇺🇸Easley, South Carolina, United States
Prisma Health Cancer Institute - Butternut
🇺🇸Greenville, South Carolina, United States
Prisma Health Cancer Institute - Faris
🇺🇸Greenville, South Carolina, United States
Prisma Health Cancer Institute - Eastside
🇺🇸Greenville, South Carolina, United States
Prisma Health Cancer Institute - Greer
🇺🇸Greer, South Carolina, United States
Prisma Health Cancer Institute - Seneca
🇺🇸Seneca, South Carolina, 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
Huntsman Cancer Institute/University of Utah
🇺🇸Salt Lake City, Utah, United States
VCU Massey Cancer Center at Stony Point
🇺🇸Richmond, Virginia, United States
Virginia Commonwealth University/Massey Cancer Center
🇺🇸Richmond, Virginia, United States
Swedish Cancer Institute-Edmonds
🇺🇸Edmonds, Washington, United States
Swedish Cancer Institute-Issaquah
🇺🇸Issaquah, Washington, United States
Swedish Medical Center-First Hill
🇺🇸Seattle, Washington, United States
Duluth Clinic Ashland
🇺🇸Ashland, Wisconsin, United States
Marshfield Medical Center-EC Cancer Center
🇺🇸Eau Claire, Wisconsin, United States
University of Wisconsin Carbone Cancer Center - Johnson Creek
🇺🇸Johnson Creek, Wisconsin, United States
Gundersen Lutheran Medical Center
🇺🇸La Crosse, Wisconsin, United States
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
🇺🇸Madison, Wisconsin, United States
University of Wisconsin Carbone Cancer Center - University Hospital
🇺🇸Madison, Wisconsin, United States
Marshfield Medical Center-Marshfield
🇺🇸Marshfield, Wisconsin, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Marshfield Medical Center - Minocqua
🇺🇸Minocqua, Wisconsin, United States
ProHealth D N Greenwald Center
🇺🇸Mukwonago, Wisconsin, United States
Froedtert and MCW Moorland Reserve Health Center
🇺🇸New Berlin, Wisconsin, United States
ProHealth Oconomowoc Memorial Hospital
🇺🇸Oconomowoc, Wisconsin, United States
Marshfield Medical Center-Rice Lake
🇺🇸Rice Lake, Wisconsin, United States
Marshfield Medical Center-River Region at Stevens Point
🇺🇸Stevens Point, Wisconsin, United States
UW Cancer Center at ProHealth Care
🇺🇸Waukesha, Wisconsin, United States
Marshfield Medical Center - Weston
🇺🇸Weston, Wisconsin, United States