Comparing Combinations of Drugs to Treat Newly Diagnosed Multiple Myeloma (NDMM) When a Stem Cell Transplant is Not a Medically Suitable Treatment
- Conditions
- Plasma Cell Myeloma
- Interventions
- Other: Quality-of-Life AssessmentOther: Questionnaire Administration
- Registration Number
- NCT05561387
- Lead Sponsor
- SWOG Cancer Research Network
- Brief Summary
This phase III trial compares three-drug induction regimens followed by double-or single-drug maintenance therapy for the treatment of newly diagnosed multiple myeloma in patients who are not receiving a stem cell transplant and are considered frail or intermediate-fit based on age, comorbidities, and functional status. Treatment for multiple myeloma includes initial treatment (induction) which is the first treatment a patient receives for cancer followed by ongoing treatment (maintenance) which is given after initial treatment to help keep the cancer from coming back. There are three combinations of four different drugs being studied. Bortezomib is one of the drugs that may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lenalidomide works by helping bone marrow to produce normal blood cells and killing cancer cells. Anti-inflammatory drugs, such as dexamethasone, lower the body's immune response and are used with other drugs in the treatment of some types of cancer. Daratumumab and hyaluronidase-fihj is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Patients receive 1 of 3 combinations of these drugs for treatment to determine which combination of study drugs works better to shrink and control multiple myeloma.
- Detailed Description
PRIMARY OBJECTIVES:
I. To compare progression-free survival (PFS) in frail or selected intermediate fit newly diagnosed multiple myeloma (NDMM) participants treated with bortezomib with lenalidomide and dexamethasone at reduced dosing (VRd-Lite) induction followed by lenalidomide maintenance (Arm 1) versus daratumumab and hyaluronidase-fihj with lenalidomide and dexamethasone (DRd) induction followed by lenalidomide maintenance (Arm 2).
II. To compare overall survival (OS) in frail or selected intermediate fit NDMM participants treated with VRd-Lite induction followed by lenalidomide maintenance (Arm 1) versus DRd induction followed by lenalidomide and daratumumab and hyaluronidase-fihj maintenance (Arm 3).
SECONDARY OBJECTIVES:
I. To compare PFS in Arm 1 versus Arm 3 II. To compare OS in Arm 1 versus Arm 2. III. To compare PFS in Arm 2 versus 3. IV. To compare the overall response rate (ORR) of Arm 1 against the ORR of Arm 2 and Arm 3.
V. To compare the safety of Arm 1 with the safety of Arm 2 and Arm 3. VI. To explore veinous thrombo-embolism (VTE) incidence in participants receiving lenalidomide during induction across the three study arms.
VII. To describe median time to response (complete response \[CR\] or better per International Myeloma Working Group \[IMWG\] criteria, very good partial response \[VGPR\] or better per IMWG criteria, partial response \[PR\] or better per IMWG criteria) on the three study arms.
PRIMARY QUALITY OF LIFE (QOL) OBJECTIVE:
I. To compare patient-reported global health status between treatment arms (Arm 1 versus the combination of Arms 2 and 3) at 9 months after randomization (end of induction therapy) using the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30).
SECONDARY QOL OBJECTIVE:
II. To compare longitudinal changes in global health status between treatment arms (Arm 1 versus the combination of Arms 2 and 3) from baseline to 9 months after randomization (end of induction therapy).
PATIENT REPORTED OUTCOMES-COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS (PRO-CTCAE) OBJECTIVE:
I. To compare selected patient-reported outcome symptoms using PRO-CTCAE items among the 3 study arms.
ADDITIONAL OBJECTIVES:
I. To compare the rate of minimal residual disease (MRD) by clonoSEQ after 9 cycles of induction in Arm 1 versus Arm 2 and Arm 3, respectively.
II. To compare the rate of MRD conversion after 1 year of maintenance in participants who were MRD positive after induction in Arm 1 versus Arm 2 and Arm 3, respectively.
III. To compare the rate of sustained MRD negativity at time points of post-induction, post-1 year maintenance in Arm 1 versus Arm 2 and Arm 3, respectively.
BANKING OBJECTIVES:
I. To bank specimens for future correlative studies.
OUTLINE: Patients are randomized to 1 of 3 arms.
ARM I (VRd-Lite):
INDUCTION CYCLES 1-9: Patients receive bortezomib subcutaneously (SC) on days 1, 8, 15, and 22 of each cycle, lenalidomide orally (PO) on days 1-21 of each cycle, and dexamethasone PO on days 1, 8, 15, and 22 of each cycle. Treatment repeats every 28 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE CYCLES 10+: Patients receive lenalidomide PO on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM II (DRd-R):
INDUCTION CYCLES 1-9: Patients receive daratumumab and hyaluronidase-fihj SC on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, and day 1 of cycles 7-9, lenalidomide PO on days 1-21 of each cycle, and dexamethasone PO on days 1, 8, 15, and 22 of each cycle. Treatment repeats every 28 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE CYCLES 10+: Patients receive lenalidomide PO on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM III (DRd-DR):
INDUCTION CYCLES 1-9: Patients receive daratumumab and hyaluronidase-fihj SC on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, and day 1 of cycles 7-9, lenalidomide PO on days 1-21 of each cycle, and dexamethasone PO on days 1, 8, 15, and 22 of each cycle. Treatment repeats every 28 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE CYCLES 10+: Patients receive daratumumab and hyaluronidase-fihj SC on day 1 of each cycle and lenalidomide PO on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 2 years, and then annually for up to 10 years.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 510
-
Participants must have documented multiple myeloma satisfying standard International Myeloma Working Group (IMWG) diagnostic criteria within 28 days prior to registration
-
Participants must have measurable disease within 28 days prior to registration as defined by any of the following:
- Immunoglobulin (Ig) G myeloma (serum monoclonal paraprotein [M-protein] level >= 0.5 gram/deciliter [g/dL] or urine M-protein level >= 200 milligram[mg]/24 hours[hrs]); OR
- IgA, IgM, IgD, or IgE multiple myeloma (serum M-protein level >= 0.2 g/dL or urine M-protein level >= 200 mg/24 hrs); OR
- Light chain multiple myeloma (serum immunoglobulin free light chain >= 10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio)
-
All disease must be assessed and documented on the baseline/pre-registration tumor assessment form
-
Participants must have a calculated myeloma frailty index (Myeloma Frailty Score Calculator; http://www.myelomafrailtyscorecalculator.net/) categorized as frail or intermediate fit (regardless of age) within 28 days prior to registration
-
For Participants Meeting "Frail" Status:
- Participants with any degree of kidney dysfunction are allowed; however, participants on dialysis are not eligible
-
For Participants Meeting "Frail" Status:
-
Hemoglobin >= 7 g/dL (must be performed within 28 days prior to registration)
- Note: growth factor and transfusion utilization are allowed if cytopenias are considered secondary to bone marrow involvement from MM)
-
-
For Participants Meeting "Frail" Status:
-
Platelets >= 50 x 10^9/L (must be performed within 28 days prior to registration)
- Note: growth factor and transfusion utilization are allowed if cytopenias are considered secondary to bone marrow involvement from MM)
-
-
For Participants Meeting "Frail" Status:
-
Absolute neutrophil count (ANC) >= 0.75 x10^9/L (must be performed within 28 days prior to registration)
- Note: growth factor and transfusion utilization are allowed if cytopenias are considered secondary to bone marrow involvement from MM)
-
-
For Participants Meeting "Intermediate Fit" Status, one or more of the following criteria must be present:
-
Kidney dysfunction showing calculated creatinine clearance (CrCl) <30 ml/min.
- Actual lab serum creatinine value with a minimum of 0.7 mg/dL.
-
Participants must have bone marrow function assessed and meet the below criteria ranges:
-
Hemoglobin between 7-8 g/dL, OR
-
Platelets between 50-75 x10^9/L, OR
-
ANC between 0.75-1 x10^9/L
- Note: growth factor and transfusion utilization are allowed as long as cytopenias are considered secondary to bone marrow involvement from MM)
-
-
Revised International Staging System (R-ISS) stage III disease
-
Note: All labs must be performed within 28 days prior to registration
-
-
Participants must have a complete medical history and physical exam within 28 days prior to registration
-
Participants must have whole body imaging within 60 days prior to registration. The recommended method of imaging is a positron emission tomography/computed tomography (PET/CT); a low-dose whole body CT scan or whole-body magnetic resonance imaging (MRI) or skeletal survey should be done only if a PET/CT scan cannot be done or is non-feasible. This must be documented in the comments section of the Onstudy form.
-
Total bilirubin =< 2 times institutional upper limit of normal (ULN) unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin =< 5 x institutional ULN (within 28 days prior to registration)
-
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 × institutional ULN (within 28 days prior to registration)
-
Participants must have adequate cardiac function, as assessed by the treating physician within 14 days prior to registration. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification and must not be assessed as class 3 or 4
-
Participants with known diabetes must show evidence of controlled disease within 14 days prior to registration. Uncontrolled diabetes is defined as: A glycosylated hemoglobin (Hg)A1C > 7
-
Participants with known human immunodeficiency virus (HIV)-infection must be receiving anti-retroviral therapy and have an undetectable viral load test on the most recent test result obtained, within 6 months prior to registration
-
All participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load on suppressive therapy within 28 days prior to registration
-
Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, participant must have an undetectable HCV viral load within 28 days prior to registration
-
Participants must have an Eastern Cooperative Oncology Group (ECOG)/Zubrod performance status score of 0-2 (Note: Participants with ECOG/Zubrod performance score [PS] 3, especially where the deterioration of PS is considered secondary to the MM diagnosis, will be allowed)
-
Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) specimen tracking system
-
Participants who are able to complete the patient-reported outcomes measures in English or Spanish must agree to participate in the PRO portion of the study
-
Participants must be informed of the investigational nature of this study and must sign and give informed consent 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 (CIRB) regulations
-
Participants must not have received any prior systemic therapy for multiple myeloma with the exception of any one or more of the following:
- An emergency use of a short course of corticosteroids (equivalent of dexamethasone 160 mg) any time before registration, or
- Up to one complete cycle of a non-daratumumab and hyaluronidase-fihj containing anti-myeloma regimen (1 cycle = 21 or 28 days depending on the regimen being used), or
- Localized palliative radiation therapy for multiple myeloma, as long as the radiation therapy is completed at least 3 days prior to starting the systemic treatment as per the study protocol.
-
Participants must not have evidence of grade 4 peripheral neuropathy prior to study registration
-
Participants must not have uncontrolled blood pressure within 14 days prior to registration. Uncontrolled blood pressure: systolic blood pressure (SBP) > 140 mmHg or diastolic blood pressure (DBP) > 90 mmHg. Participants are permitted to be receiving multiple anti-hypertensive medications (unless otherwise indicated in the study). All blood pressure measurements within the 14 days prior to registration must be SBP =< 140 and DBP =< 90. A participant with a single blood pressure elevation who upon rechecking has a normal blood pressure will remain eligible at the discretion of the registering investigator.
-
Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
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Participants must not be pregnant or nursing. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 24 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I (VRd-Lite) Quality-of-Life Assessment INDUCTION CYCLES 1-9: Patients receive bortezomib SC on days 1, 8, 15, and 22 of each cycle, lenalidomide PO on days 1-21 of each cycle, and dexamethasone PO on days 1, 8, 15, and 22 of each cycle. Treatment repeats every 28 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE CYCLES 10+: Patients receive lenalidomide PO on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm I (VRd-Lite) Questionnaire Administration INDUCTION CYCLES 1-9: Patients receive bortezomib SC on days 1, 8, 15, and 22 of each cycle, lenalidomide PO on days 1-21 of each cycle, and dexamethasone PO on days 1, 8, 15, and 22 of each cycle. Treatment repeats every 28 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE CYCLES 10+: Patients receive lenalidomide PO on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm II (DRd-R) Quality-of-Life Assessment INDUCTION CYCLES 1-9: Patients receive daratumumab and hyaluronidase-fihj SC on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, and day 1 of cycles 7-9, lenalidomide PO on days 1-21 of each cycle, and dexamethasone PO on days 1, 8, 15, and 22 of each cycle. Treatment repeats every 28 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE CYCLES 10+: Patients receive lenalidomide PO on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm II (DRd-R) Questionnaire Administration INDUCTION CYCLES 1-9: Patients receive daratumumab and hyaluronidase-fihj SC on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, and day 1 of cycles 7-9, lenalidomide PO on days 1-21 of each cycle, and dexamethasone PO on days 1, 8, 15, and 22 of each cycle. Treatment repeats every 28 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE CYCLES 10+: Patients receive lenalidomide PO on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm III (DRd-DR): Quality-of-Life Assessment INDUCTION CYCLES 1-9: Patients receive daratumumab and hyaluronidase-fihj SC on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, and day 1 of cycles 7-9, lenalidomide PO on days 1-21 of each cycle, and dexamethasone PO on days 1, 8, 15, and 22 of each cycle. Treatment repeats every 28 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE CYCLES 10+: Patients receive daratumumab and hyaluronidase-fihj SC on day 1 of each cycle and lenalidomide PO on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm III (DRd-DR): Questionnaire Administration INDUCTION CYCLES 1-9: Patients receive daratumumab and hyaluronidase-fihj SC on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, and day 1 of cycles 7-9, lenalidomide PO on days 1-21 of each cycle, and dexamethasone PO on days 1, 8, 15, and 22 of each cycle. Treatment repeats every 28 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE CYCLES 10+: Patients receive daratumumab and hyaluronidase-fihj SC on day 1 of each cycle and lenalidomide PO on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm II (DRd-R) Daratumumab and Hyaluronidase-fihj INDUCTION CYCLES 1-9: Patients receive daratumumab and hyaluronidase-fihj SC on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, and day 1 of cycles 7-9, lenalidomide PO on days 1-21 of each cycle, and dexamethasone PO on days 1, 8, 15, and 22 of each cycle. Treatment repeats every 28 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE CYCLES 10+: Patients receive lenalidomide PO on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm III (DRd-DR): Daratumumab and Hyaluronidase-fihj INDUCTION CYCLES 1-9: Patients receive daratumumab and hyaluronidase-fihj SC on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, and day 1 of cycles 7-9, lenalidomide PO on days 1-21 of each cycle, and dexamethasone PO on days 1, 8, 15, and 22 of each cycle. Treatment repeats every 28 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE CYCLES 10+: Patients receive daratumumab and hyaluronidase-fihj SC on day 1 of each cycle and lenalidomide PO on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm I (VRd-Lite) Bortezomib INDUCTION CYCLES 1-9: Patients receive bortezomib SC on days 1, 8, 15, and 22 of each cycle, lenalidomide PO on days 1-21 of each cycle, and dexamethasone PO on days 1, 8, 15, and 22 of each cycle. Treatment repeats every 28 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE CYCLES 10+: Patients receive lenalidomide PO on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm I (VRd-Lite) Dexamethasone INDUCTION CYCLES 1-9: Patients receive bortezomib SC on days 1, 8, 15, and 22 of each cycle, lenalidomide PO on days 1-21 of each cycle, and dexamethasone PO on days 1, 8, 15, and 22 of each cycle. Treatment repeats every 28 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE CYCLES 10+: Patients receive lenalidomide PO on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm I (VRd-Lite) Lenalidomide INDUCTION CYCLES 1-9: Patients receive bortezomib SC on days 1, 8, 15, and 22 of each cycle, lenalidomide PO on days 1-21 of each cycle, and dexamethasone PO on days 1, 8, 15, and 22 of each cycle. Treatment repeats every 28 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE CYCLES 10+: Patients receive lenalidomide PO on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm II (DRd-R) Dexamethasone INDUCTION CYCLES 1-9: Patients receive daratumumab and hyaluronidase-fihj SC on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, and day 1 of cycles 7-9, lenalidomide PO on days 1-21 of each cycle, and dexamethasone PO on days 1, 8, 15, and 22 of each cycle. Treatment repeats every 28 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE CYCLES 10+: Patients receive lenalidomide PO on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm II (DRd-R) Lenalidomide INDUCTION CYCLES 1-9: Patients receive daratumumab and hyaluronidase-fihj SC on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, and day 1 of cycles 7-9, lenalidomide PO on days 1-21 of each cycle, and dexamethasone PO on days 1, 8, 15, and 22 of each cycle. Treatment repeats every 28 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE CYCLES 10+: Patients receive lenalidomide PO on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm III (DRd-DR): Dexamethasone INDUCTION CYCLES 1-9: Patients receive daratumumab and hyaluronidase-fihj SC on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, and day 1 of cycles 7-9, lenalidomide PO on days 1-21 of each cycle, and dexamethasone PO on days 1, 8, 15, and 22 of each cycle. Treatment repeats every 28 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE CYCLES 10+: Patients receive daratumumab and hyaluronidase-fihj SC on day 1 of each cycle and lenalidomide PO on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm III (DRd-DR): Lenalidomide INDUCTION CYCLES 1-9: Patients receive daratumumab and hyaluronidase-fihj SC on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, and day 1 of cycles 7-9, lenalidomide PO on days 1-21 of each cycle, and dexamethasone PO on days 1, 8, 15, and 22 of each cycle. Treatment repeats every 28 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE CYCLES 10+: Patients receive daratumumab and hyaluronidase-fihj SC on day 1 of each cycle and lenalidomide PO on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Progression free survival (PFS) of Arm 1 versus (vs.) Arm 2 From date of randomization to date of first documentation of progression or symptomatic deterioration, or death due to any cause, or assessed up to 10 years Analysis of each of the dual primary endpoints will be performed using a stratified log-rank test for comparison between arms. The analyses will be stratified according to frailty score (frail vs. intermediate fit), presence of one or more high-risk abnormalities by fluorescence in situ hybridization (iFISH) (yes vs. no), and prior therapy (yes vs. no). All eligible participants will be considered in analyses of the dual primary endpoints, according to their assigned arm at randomization.
Overall survival (OS) of Arm 1 vs. Arm 3 From date of randomization to date of death due to any cause, or assessed up to 10 years Analysis of each of the dual primary endpoints will be performed using a stratified log-rank test for comparison between arms. The analyses will be stratified according to frailty score (frail vs. intermediate fit), presence of one or more high-risk abnormalities by iFISH (yes vs. no), and prior therapy (yes vs. no). All eligible participants will be considered in analyses of the dual primary endpoints, according to their assigned arm at randomization.
- Secondary Outcome Measures
Name Time Method Overall response rate (ORR) Up to 10 years ORR is defined as the percentage of participants achieving a best response of partial response (PR) or better while on study. ORR will be reported with a binomial confidence interval. Time to response will be analyzed using the cumulative incidence competing risks method.
Time to complete response (CR) The time from the date of registration to the date of the first documented incidence of a response of CR or better, assessed up to 10 years All eligible participants will be considered in analyses of the secondary endpoints, according to their assigned arm at randomization, and with participants who go off-study prior to response assessment considered as non-responders for the analysis of response rate and as censored at the time of removal from study for the analysis of time to response. Time to response will be analyzed using the cumulative incidence competing risks method.
Time to very good partial response (VGFR) The time from the date of registration to the date of the first documented incidence of a response of VGPR or better, assessed up to 10 years All eligible participants will be considered in analyses of the secondary endpoints, according to their assigned arm at randomization, and with participants who go off-study prior to response assessment considered as non-responders for the analysis of response rate and as censored at the time of removal from study for the analysis of time to response. Time to response will be analyzed using the cumulative incidence competing risks method.
PFS From date of randomization to date of first documentation of progression or symptomatic deterioration, or death due to any cause, or assessed up to 10 years Analysis of PFS and OS endpoints will be performed using a stratified log-rank test for comparison between arms, with stratification according to frailty score (frail vs. intermediate fit) presence of one or more high-risk abnormalities by iFISH (yes vs. no) and prior therapy (yes vs. no).
Minimal residual disease (MRD) At 9 months of induction therapy and 1 year of maintenance therapy The rate of MRD negativity will be calculated at each timepoint as the number of patients who are MRD negative divided by the number of patients who were eligible, analyzable and assessable for clinical response assessment at that timepoint. Rates of MRD negativity will be compared using a two-arm binomial test.
Patient-reported toxicity (PRO-Common Terminology Criteria for Adverse Events [CTCAE]) At baseline, at each treatment cycle up to month 18 from randomization, and at discontinuation of treatment PRO-CTCAE is intended to enhance the quality of adverse event data reporting in clinical trials, provide data that complements and extends the information provided by clinician reporting using CTCAE, represent the patient perspective of the experience of symptomatic adverse events (AEs), and improve detection of potentially serious adverse events. Descriptive statistics will be used to summarize selected PRO-CTCAEs tabulated at each cycle overall and by arm. We will examine the extent to which PRO-CTCAEs with provider reported AEs are correlated and evaluate differences in incidence and worst severity.
OS From date of randomization to date of death due to any cause, or assessed up to 10 years Analysis of PFS and OS endpoints will be performed using a stratified log-rank test for comparison between arms, with stratification according to frailty score (frail vs. intermediate fit) presence of one or more high-risk abnormalities by iFISH (yes vs. no) and prior therapy (yes vs. no).
Patient report out comes (PRO) quality-of-life (QOL) At baseline and months 1, 3, 9, and 18 after randomization We will use the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 (version 3). This instrument includes questions broadly applicable to all cancer patients, assessing 5 functional domains (physical, role, cognitive, emotional, social) and 8 symptoms (fatigue, pain, nausea/vomiting, dyspnea, loss of appetite, insomnia, constipation, diarrhea), together with financial problems and global quality of life.
Time to PR The time from the date of registration to the date of the first documented incidence of a response of PR or better, assessed up to 10 years All eligible participants will be considered in analyses of the secondary endpoints, according to their assigned arm at randomization, and with participants who go off-study prior to response assessment considered as non-responders for the analysis of response rate and as censored at the time of removal from study for the analysis of time to response. Time to response will be analyzed using the cumulative incidence competing risks method.
Trial Locations
- Locations (396)
Saint Luke's Cancer Institute - Twin Falls
🇺🇸Twin Falls, Idaho, United States
Illinois CancerCare-Carthage
🇺🇸Carthage, Illinois, United States
Saint Anthony's Health
🇺🇸Alton, Illinois, United States
Illinois CancerCare-Eureka
🇺🇸Eureka, Illinois, United States
Memorial Hospital of Carbondale
🇺🇸Carbondale, Illinois, United States
Loyola Center for Health at Burr Ridge
🇺🇸Burr Ridge, Illinois, United States
Saint Luke's Cancer Institute - Boise
🇺🇸Boise, Idaho, United States
Jupiter Medical Center
🇺🇸Jupiter, Florida, United States
Rush - Copley Medical Center
🇺🇸Aurora, Illinois, United States
Saint Luke's Cancer Institute - Meridian
🇺🇸Meridian, Idaho, United States
Illinois CancerCare-Bloomington
🇺🇸Bloomington, Illinois, United States
Illinois CancerCare-Peoria
🇺🇸Peoria, Illinois, United States
Saint Luke's Cancer Institute - Fruitland
🇺🇸Fruitland, Idaho, United States
Saint Mary's Hospital
🇺🇸Centralia, Illinois, United States
Saint Joseph Medical Center
🇺🇸Bloomington, Illinois, United States
SIH Cancer Institute
🇺🇸Carterville, Illinois, United States
Saint Luke's Cancer Institute - Nampa
🇺🇸Nampa, Idaho, United States
Carle Cancer Center
🇺🇸Urbana, Illinois, United States
Newland Medical Associates-Clarkston
🇺🇸Clarkston, Michigan, United States
Illinois CancerCare - Washington
🇺🇸Washington, Illinois, United States
Mission Cancer and Blood - Ankeny
🇺🇸Ankeny, Iowa, United States
Saint Joseph Mount Sterling
🇺🇸Mount Sterling, Kentucky, United States
Illinois CancerCare-Ottawa Clinic
🇺🇸Ottawa, Illinois, United States
Valley Radiation Oncology
🇺🇸Peru, Illinois, United States
Northwest Cancer Center - Hobart
🇺🇸Hobart, Indiana, United States
Northwest Cancer Center - Valparaiso
🇺🇸Valparaiso, Indiana, United States
University of Iowa Healthcare Cancer Services Quad Cities
🇺🇸Bettendorf, Iowa, United States
Illinois CancerCare-Princeton
🇺🇸Princeton, Illinois, United States
Saint Mary Medical Center
🇺🇸Hobart, Indiana, United States
Caro Cancer Center
🇺🇸Caro, Michigan, United States
Genesee Cancer and Blood Disease Treatment Center
🇺🇸Flint, Michigan, United States
Illinois CancerCare-Pekin
🇺🇸Pekin, Illinois, United States
The Carle Foundation Hospital
🇺🇸Urbana, Illinois, United States
Saint Joseph Hospital East
🇺🇸Lexington, Kentucky, United States
Northwest Oncology LLC
🇺🇸Dyer, Indiana, United States
Reid Health
🇺🇸Richmond, Indiana, United States
Physicians' Clinic of Iowa PC
🇺🇸Cedar Rapids, Iowa, United States
Saint Joseph Mercy Canton
🇺🇸Canton, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology - Brighton
🇺🇸Brighton, Michigan, United States
Saint Joseph London
🇺🇸London, Kentucky, United States
Genesee Hematology Oncology PC
🇺🇸Flint, Michigan, United States
Commonwealth Cancer Center-Corbin
🇺🇸Corbin, Kentucky, United States
Great Lakes Cancer Management Specialists-Doctors Park
🇺🇸East China Township, Michigan, United States
Great Lakes Cancer Management Specialists-Macomb Medical Campus
🇺🇸Macomb, Michigan, United States
Minnesota Oncology - Burnsville
🇺🇸Burnsville, Minnesota, United States
Miller-Dwan Hospital
🇺🇸Duluth, Minnesota, United States
Trinity Health Saint Mary Mercy Livonia Hospital
🇺🇸Livonia, Michigan, United States
Ascension Borgess Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Essentia Health - Baxter Clinic
🇺🇸Baxter, Minnesota, United States
Munson Medical Center
🇺🇸Traverse City, Michigan, United States
Essentia Health Hibbing Clinic
🇺🇸Hibbing, Minnesota, United States
Park Nicollet Clinic - Saint Louis Park
🇺🇸Saint Louis Park, Minnesota, United States
Capital Region Southwest Campus
🇺🇸Jefferson City, Missouri, United States
Heartland Regional Medical Center
🇺🇸Saint Joseph, Missouri, United States
Ascension Saint Joseph Hospital
🇺🇸Tawas City, Michigan, United States
University of Michigan Health - West
🇺🇸Wyoming, Michigan, United States
Cambridge Medical Center
🇺🇸Cambridge, Minnesota, United States
Fairview Clinics and Surgery Center Maple Grove
🇺🇸Maple Grove, Minnesota, United States
Saint John Macomb-Oakland Hospital
🇺🇸Warren, Michigan, United States
Essentia Health Saint Mary's Medical Center
🇺🇸Duluth, Minnesota, United States
CoxHealth South Hospital
🇺🇸Springfield, Missouri, United States
North Memorial Medical Health Center
🇺🇸Robbinsdale, Minnesota, United States
Fairview Northland Medical Center
🇺🇸Princeton, Minnesota, United States
Research Medical Center
🇺🇸Kansas City, Missouri, United States
Essentia Health - Jamestown Clinic
🇺🇸Jamestown, North Dakota, United States
Saint John's Hospital - Healtheast
🇺🇸Maplewood, Minnesota, United States
Essentia Health - Park Rapids
🇺🇸Park Rapids, Minnesota, United States
Cox Cancer Center Branson
🇺🇸Branson, Missouri, United States
Regions Hospital
🇺🇸Saint Paul, Minnesota, United States
Lovelace Medical Center-Saint Joseph Square
🇺🇸Albuquerque, New Mexico, United States
Midlands Community Hospital
🇺🇸Papillion, Nebraska, United States
Fairview Lakes Medical Center
🇺🇸Wyoming, Minnesota, United States
Freeman Health System
🇺🇸Joplin, Missouri, United States
Essentia Health Cancer Center-South University Clinic
🇺🇸Fargo, North Dakota, United States
Presbyterian Kaseman Hospital
🇺🇸Albuquerque, New Mexico, United States
CHI Health Good Samaritan
🇺🇸Kearney, Nebraska, United States
Sanford Bismarck Medical Center
🇺🇸Bismarck, North Dakota, United States
VCU Massey Cancer Center at Stony Point
🇺🇸Richmond, Virginia, United States
Virginia Commonwealth University/Massey Cancer Center
🇺🇸Richmond, Virginia, United States
Providence Regional Cancer System-Centralia
🇺🇸Centralia, Washington, United States
Virginia Cancer Institute
🇺🇸Richmond, Virginia, United States
Sovah Health Martinsville
🇺🇸Martinsville, Virginia, United States
Providence Regional Cancer System-Shelton
🇺🇸Shelton, Washington, United States
MD Anderson in Sugar Land
🇺🇸Sugar Land, Texas, United States
Harrison Medical Center
🇺🇸Bremerton, Washington, United States
MD Anderson League City
🇺🇸League City, Texas, United States
VCU Community Memorial Health Center
🇺🇸South Hill, Virginia, United States
PeaceHealth Saint John Medical Center
🇺🇸Longview, Washington, United States
PeaceHealth Saint Joseph Medical Center
🇺🇸Bellingham, Washington, United States
Providence Regional Cancer Partnership
🇺🇸Everett, Washington, United States
Swedish Cancer Institute-Issaquah
🇺🇸Issaquah, Washington, United States
Essentia Health-Hayward Clinic
🇺🇸Hayward, Wisconsin, United States
Marshfield Medical Center - Neillsville
🇺🇸Neillsville, Wisconsin, United States
Marshfield Medical Center-Marshfield
🇺🇸Marshfield, Wisconsin, United States
PeaceHealth United General Medical Center
🇺🇸Sedro-Woolley, Washington, United States
Aspirus Cancer Care - Wisconsin Rapids
🇺🇸Wisconsin Rapids, Wisconsin, United States
Marshfield Clinic - Wisconsin Rapids Center
🇺🇸Wisconsin Rapids, Wisconsin, United States
West Virginia University Charleston Division
🇺🇸Charleston, West Virginia, United States
Duluth Clinic Ashland
🇺🇸Ashland, Wisconsin, United States
Marshfield Medical Center-Rice Lake
🇺🇸Rice Lake, Wisconsin, United States
Northwest Wisconsin Cancer Center
🇺🇸Ashland, Wisconsin, United States
Marshfield Clinic-Minocqua Center
🇺🇸Minocqua, Wisconsin, United States
Mercy Cancer Center - Carmichael
🇺🇸Carmichael, California, United States
IU Health North Hospital
🇺🇸Carmel, Indiana, United States
Greater Baltimore Medical Center
🇺🇸Baltimore, Maryland, United States
Swedish Cancer Institute-Edmonds
🇺🇸Edmonds, Washington, United States
ThedaCare Regional Cancer Center
🇺🇸Appleton, Wisconsin, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
🇺🇸Houston, Texas, United States
Ben Taub General Hospital
🇺🇸Houston, Texas, United States
Michael E DeBakey VA Medical Center
🇺🇸Houston, Texas, United States
M D Anderson Cancer Center
🇺🇸Houston, Texas, United States
MD Anderson West Houston
🇺🇸Houston, Texas, United States
Swedish Medical Center-Ballard Campus
🇺🇸Seattle, Washington, United States
Swedish Medical Center-Cherry Hill
🇺🇸Seattle, Washington, United States
Swedish Medical Center-First Hill
🇺🇸Seattle, Washington, United States
Indiana University/Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
Saint Catherine Hospital
🇺🇸Indianapolis, Indiana, United States
Good Samaritan Hospital - Cincinnati
🇺🇸Cincinnati, Ohio, United States
TriHealth Cancer Institute-Westside
🇺🇸Cincinnati, Ohio, United States
TriHealth Cancer Institute-Anderson
🇺🇸Cincinnati, Ohio, United States
Abbott-Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
Hennepin County Medical Center
🇺🇸Minneapolis, Minnesota, United States
Health Partners Inc
🇺🇸Minneapolis, Minnesota, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
University of Rochester
🇺🇸Rochester, New York, United States
Central Care Cancer Center - Garden City
🇺🇸Garden City, Kansas, United States
Central Care Cancer Center - Great Bend
🇺🇸Great Bend, Kansas, United States
Porter Adventist Hospital
🇺🇸Denver, Colorado, United States
Ascension Saint John Hospital
🇺🇸Detroit, Michigan, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Providence Saint Vincent Medical Center
🇺🇸Portland, Oregon, United States
Saint Francis Medical Center
🇺🇸Cape Girardeau, Missouri, United States
Mercy Hospital Joplin
🇺🇸Joplin, Missouri, United States
Delbert Day Cancer Institute at PCRMC
🇺🇸Rolla, Missouri, United States
Mercy Hospital South
🇺🇸Saint Louis, Missouri, United States
Mercy Clinic-Rolla-Cancer and Hematology
🇺🇸Rolla, Missouri, United States
Missouri Baptist Medical Center
🇺🇸Saint Louis, Missouri, United States
Mercy Hospital Saint Louis
🇺🇸Saint Louis, Missouri, United States
Mercy Hospital Washington
🇺🇸Washington, Missouri, United States
Sainte Genevieve County Memorial Hospital
🇺🇸Sainte Genevieve, Missouri, United States
Sanford South University Medical Center
🇺🇸Fargo, North Dakota, United States
Essentia Health Saint Mary's - Detroit Lakes Clinic
🇺🇸Detroit Lakes, Minnesota, United States
Essentia Health - Deer River Clinic
🇺🇸Deer River, Minnesota, United States
Minnesota Oncology Hematology PA-Maplewood
🇺🇸Maplewood, Minnesota, United States
Unity Hospital
🇺🇸Fridley, Minnesota, United States
Lakeview Hospital
🇺🇸Stillwater, Minnesota, United States
Rice Memorial Hospital
🇺🇸Willmar, Minnesota, United States
Sanford Thief River Falls Medical Center
🇺🇸Thief River Falls, Minnesota, United States
Mercy Cancer Center - Elk Grove
🇺🇸Elk Grove, California, United States
Mercy UC Davis Cancer Center
🇺🇸Merced, California, United States
Saint Mary's Oncology/Hematology Associates of Marlette
🇺🇸Marlette, Michigan, United States
Trinity Health Muskegon Hospital
🇺🇸Muskegon, Michigan, United States
Corewell Health Lakeland Hospitals - Niles Hospital
🇺🇸Niles, Michigan, United States
Newland Medical Associates-Pontiac
🇺🇸Pontiac, Michigan, United States
Corewell Health Reed City Hospital
🇺🇸Reed City, Michigan, United States
Lakeland Medical Center Saint Joseph
🇺🇸Saint Joseph, Michigan, United States
Advanced Breast Care Center PLLC
🇺🇸Warren, Michigan, United States
Huron Gastroenterology PC
🇺🇸Ypsilanti, Michigan, United States
Cancer Care Specialists of Illinois - Decatur
🇺🇸Decatur, Illinois, United States
Crossroads Cancer Center
🇺🇸Effingham, Illinois, United States
Illinois CancerCare-Galesburg
🇺🇸Galesburg, Illinois, United States
Methodist Medical Center of Illinois
🇺🇸Peoria, Illinois, United States
Cancer Care Center of O'Fallon
🇺🇸O'Fallon, Illinois, United States
Memorial Medical Center
🇺🇸Springfield, Illinois, United States
Rush-Copley Healthcare Center
🇺🇸Yorkville, Illinois, United States
Community Medical Center
🇺🇸Scranton, Pennsylvania, United States
University of Iowa/Holden Comprehensive Cancer Center
🇺🇸Iowa City, Iowa, United States
Greater Regional Medical Center
🇺🇸Creston, Iowa, United States
Marshfield Clinic-Wausau Center
🇺🇸Wausau, Wisconsin, United States
Essentia Health-Spooner Clinic
🇺🇸Spooner, Wisconsin, United States
Ascension Saint Michael's Hospital
🇺🇸Stevens Point, Wisconsin, United States
Marshfield Medical Center - Weston
🇺🇸Weston, Wisconsin, United States
Rocky Mountain Regional VA Medical Center
🇺🇸Aurora, Colorado, United States
Alegent Health Bergan Mercy Medical Center
🇺🇸Omaha, Nebraska, United States
Mayo Clinic in Rochester
🇺🇸Rochester, Minnesota, 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
Saint Mary's Oncology/Hematology Associates of West Branch
🇺🇸West Branch, Michigan, United States
West Michigan Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
🇺🇸Ypsilanti, Michigan, United States
Western Illinois Cancer Treatment Center
🇺🇸Galesburg, Illinois, United States
Alaska Breast Care and Surgery LLC
🇺🇸Anchorage, Alaska, United States
Anchorage Associates in Radiation Medicine
🇺🇸Anchorage, Alaska, United States
Anchorage Radiation Therapy Center
🇺🇸Anchorage, Alaska, United States
Alaska Oncology and Hematology LLC
🇺🇸Anchorage, Alaska, United States
Alaska Women's Cancer Care
🇺🇸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
Cancer Center at Saint Joseph's
🇺🇸Phoenix, Arizona, United States
Mercy Hospital Fort Smith
🇺🇸Fort Smith, Arkansas, United States
CARTI Cancer Center
🇺🇸Little Rock, Arkansas, United States
John L McClellan Memorial Veterans Hospital
🇺🇸Little Rock, Arkansas, United States
Mission Hope Medical Oncology - Arroyo Grande
🇺🇸Arroyo Grande, California, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Providence Saint Joseph Medical Center/Disney Family Cancer Center
🇺🇸Burbank, California, United States
Marshall Cancer Center
🇺🇸Cameron Park, California, United States
Mercy San Juan Medical Center
🇺🇸Carmichael, California, United States
Fremont - Rideout Cancer Center
🇺🇸Marysville, California, United States
Mercy Cancer Center - Rocklin
🇺🇸Rocklin, California, United States
Providence Queen of The Valley
🇺🇸Napa, California, United States
Pacific Central Coast Health Center-San Luis Obispo
🇺🇸San Luis Obispo, California, United States
Mission Hope Medical Oncology - Santa Maria
🇺🇸Santa Maria, California, United States
Woodland Memorial Hospital
🇺🇸Woodland, California, United States
Providence Medical Foundation - Santa Rosa
🇺🇸Santa Rosa, California, United States
Providence Santa Rosa Memorial Hospital
🇺🇸Santa Rosa, California, United States
Gene Upshaw Memorial Tahoe Forest Cancer Center
🇺🇸Truckee, California, United States
Penrose-Saint Francis Healthcare
🇺🇸Colorado Springs, Colorado, United States
Rocky Mountain Cancer Centers-Penrose
🇺🇸Colorado Springs, Colorado, United States
Saint Francis Cancer Center
🇺🇸Colorado Springs, Colorado, United States
Mercy Medical Center
🇺🇸Durango, Colorado, United States
Southwest Oncology PC
🇺🇸Durango, Colorado, United States
Saint Anthony Hospital
🇺🇸Lakewood, Colorado, United States
Parker Adventist Hospital
🇺🇸Parker, Colorado, United States
Littleton Adventist Hospital
🇺🇸Littleton, Colorado, United States
Longmont United Hospital
🇺🇸Longmont, Colorado, 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
Smilow Cancer Hospital Care Center at Long Ridge
🇺🇸Stamford, Connecticut, United States
Smilow Cancer Hospital-Torrington Care Center
🇺🇸Torrington, Connecticut, United States
Yale-New Haven Hospital North Haven Medical Center
🇺🇸North Haven, Connecticut, United States
Smilow Cancer Hospital-Waterbury Care Center
🇺🇸Waterbury, Connecticut, United States
Smilow Cancer Hospital Care Center-Trumbull
🇺🇸Trumbull, Connecticut, United States
Smilow Cancer Hospital Care Center - Waterford
🇺🇸Waterford, Connecticut, United States
Mayo Clinic in Florida
🇺🇸Jacksonville, Florida, United States
Illinois CancerCare-Canton
🇺🇸Canton, Illinois, United States
Centralia Oncology Clinic
🇺🇸Centralia, 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
Loyola Medicine Homer Glen
🇺🇸Homer Glen, Illinois, United States
Edward Hines Jr VA Hospital
🇺🇸Hines, Illinois, United States
Illinois CancerCare-Kewanee Clinic
🇺🇸Kewanee, Illinois, United States
Carle Physician Group-Mattoon/Charleston
🇺🇸Mattoon, Illinois, United States
Illinois CancerCare-Macomb
🇺🇸Macomb, Illinois, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Marjorie Weinberg Cancer Center at Loyola-Gottlieb
🇺🇸Melrose Park, Illinois, United States
Good Samaritan Regional Health Center
🇺🇸Mount Vernon, Illinois, United States
HSHS Saint Elizabeth's Hospital
🇺🇸O'Fallon, Illinois, United States
Illinois CancerCare-Peru
🇺🇸Peru, Illinois, United States
Southern Illinois University School of Medicine
🇺🇸Springfield, Illinois, United States
Springfield Clinic
🇺🇸Springfield, Illinois, United States
Northwest Cancer Center - Main Campus
🇺🇸Crown Point, Indiana, United States
The Community Hospital
🇺🇸Munster, Indiana, United States
Mission Cancer and Blood - Laurel
🇺🇸Des Moines, Iowa, United States
Mercy Medical Center-West Lakes
🇺🇸West Des Moines, Iowa, United States
Flaget Memorial Hospital
🇺🇸Bardstown, Kentucky, United States
Saint Joseph Hospital
🇺🇸Lexington, Kentucky, United States
Bronson Battle Creek
🇺🇸Battle Creek, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology - Canton
🇺🇸Canton, Michigan, United States
Hurley Medical Center
🇺🇸Flint, Michigan, United States
Trinity Health Grand Rapids Hospital
🇺🇸Grand Rapids, Michigan, United States
Academic Hematology Oncology Specialists
🇺🇸Grosse Pointe Woods, Michigan, United States
Bronson Methodist Hospital
🇺🇸Kalamazoo, Michigan, United States
Borgess Medical Center
🇺🇸Kalamazoo, Michigan, United States
University of Michigan Health - Sparrow Lansing
🇺🇸Lansing, Michigan, United States
Cancer and Hematology Centers of Western Michigan - Norton Shores
🇺🇸Norton Shores, Michigan, United States
Hope Cancer Center
🇺🇸Pontiac, Michigan, United States
Bhadresh Nayak MD PC-Sterling Heights
🇺🇸Sterling Heights, Michigan, United States
Oncology Hematology Associates of Saginaw Valley PC
🇺🇸Saginaw, Michigan, United States
Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
🇺🇸Saint Joseph, Michigan, United States
Great Lakes Cancer Management Specialists-Macomb Professional Building
🇺🇸Warren, Michigan, United States
Macomb Hematology Oncology PC
🇺🇸Warren, Michigan, United States
Michigan Breast Specialists-Warren
🇺🇸Warren, Michigan, United States
Riverwood Healthcare Center
🇺🇸Aitkin, Minnesota, United States
Essentia Health Saint Joseph's Medical Center
🇺🇸Brainerd, Minnesota, United States
Essentia Health Cancer Center
🇺🇸Duluth, Minnesota, United States
Mercy Hospital
🇺🇸Coon Rapids, Minnesota, United States
Essentia Health - Ely Clinic
🇺🇸Ely, Minnesota, United States
Essentia Health - Fosston
🇺🇸Fosston, Minnesota, United States
Essentia Health - International Falls Clinic
🇺🇸International Falls, Minnesota, United States
Monticello Cancer Center
🇺🇸Monticello, Minnesota, United States
New Ulm Medical Center
🇺🇸New Ulm, Minnesota, United States
Saint Francis Regional Medical Center
🇺🇸Shakopee, 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
Sanford Cancer Center Worthington
🇺🇸Worthington, Minnesota, United States
Minnesota Oncology Hematology PA-Woodbury
🇺🇸Woodbury, Minnesota, United States
Central Care Cancer Center - Bolivar
🇺🇸Bolivar, Missouri, United States
Lake Regional Hospital
🇺🇸Osage Beach, Missouri, United States
Saint Louis Cancer and Breast Institute-South City
🇺🇸Saint Louis, Missouri, United States
Missouri Baptist Sullivan Hospital
🇺🇸Sullivan, Missouri, United States
BJC Outpatient Center at Sunset Hills
🇺🇸Sunset Hills, Missouri, United States
Saint Elizabeth Regional Medical Center
🇺🇸Lincoln, Nebraska, United States
Exeter Hospital
🇺🇸Exeter, New Hampshire, United States
Saint Patrick Hospital - Community Hospital
🇺🇸Missoula, Montana, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
🇺🇸New York, New York, United States
Presbyterian Rust Medical Center/Jorgensen Cancer Center
🇺🇸Rio Rancho, New Mexico, United States
Southpointe-Sanford Medical Center Fargo
🇺🇸Fargo, North Dakota, United States
Indu and Raj Soin Medical Center
🇺🇸Beavercreek, Ohio, United States
Sanford Broadway Medical Center
🇺🇸Fargo, North Dakota, United States
Sanford Roger Maris Cancer Center
🇺🇸Fargo, North Dakota, United States
Saint Elizabeth Boardman Hospital
🇺🇸Boardman, Ohio, United States
Dayton Physicians LLC-Miami Valley South
🇺🇸Centerville, Ohio, United States
Bethesda North Hospital
🇺🇸Cincinnati, Ohio, United States
Oncology Hematology Care Inc-Kenwood
🇺🇸Cincinnati, Ohio, United States
Dayton Physician LLC-Miami Valley Hospital North
🇺🇸Dayton, Ohio, United States
Blanchard Valley Hospital
🇺🇸Findlay, Ohio, United States
Armes Family Cancer Center
🇺🇸Findlay, Ohio, United States
Orion Cancer Care
🇺🇸Findlay, Ohio, United States
Dayton Physicians LLC-Atrium
🇺🇸Franklin, Ohio, United States
Dayton Physicians LLC-Wayne
🇺🇸Greenville, Ohio, United States
Wayne Hospital
🇺🇸Greenville, Ohio, United States
Kettering Medical Center
🇺🇸Kettering, Ohio, United States
Saint Joseph Warren Hospital
🇺🇸Warren, Ohio, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Saint Elizabeth Youngstown Hospital
🇺🇸Youngstown, Ohio, United States
Dayton Physicians LLC - Troy
🇺🇸Troy, Ohio, United States
Saint Charles Health System
🇺🇸Bend, Oregon, United States
Mercy Hospital Oklahoma City
🇺🇸Oklahoma City, Oklahoma, United States
Clackamas Radiation Oncology Center
🇺🇸Clackamas, Oregon, United States
Providence Cancer Institute Clackamas Clinic
🇺🇸Clackamas, Oregon, United States
Bay Area Hospital
🇺🇸Coos Bay, Oregon, United States
Providence Newberg Medical Center
🇺🇸Newberg, Oregon, United States
Rogue Valley Medical Center
🇺🇸Medford, Oregon, United States
Providence Willamette Falls Medical Center
🇺🇸Oregon City, Oregon, United States
Lehigh Valley Hospital-Cedar Crest
🇺🇸Allentown, Pennsylvania, United States
Saint Charles Health System-Redmond
🇺🇸Redmond, Oregon, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
Lehigh Valley Hospital - Muhlenberg
🇺🇸Bethlehem, Pennsylvania, United States
Lehigh Valley Hospital-Hazleton
🇺🇸Hazleton, Pennsylvania, United States
Pocono Medical Center
🇺🇸East Stroudsburg, Pennsylvania, United States
Geisinger Medical Oncology-Lewisburg
🇺🇸Lewisburg, Pennsylvania, United States
Prisma Health Cancer Institute - Spartanburg
🇺🇸Boiling Springs, 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
Avera Cancer Institute
🇺🇸Sioux Falls, South Dakota, United States
Prisma Health Cancer Institute - Seneca
🇺🇸Seneca, South Carolina, United States
MD Anderson in The Woodlands
🇺🇸Conroe, Texas, United States
Avera Cancer Institute at Yankton
🇺🇸Yankton, South Dakota, United States
Sanford USD Medical Center - Sioux Falls
🇺🇸Sioux Falls, South Dakota, United States
Providence Regional Cancer System-Aberdeen
🇺🇸Aberdeen, Washington, United States
Kadlec Clinic Hematology and Oncology
🇺🇸Kennewick, Washington, United States
Providence Regional Cancer System-Lacey
🇺🇸Lacey, Washington, United States
Providence Regional Cancer System-Yelm
🇺🇸Yelm, Washington, United States
Providence Saint Mary Regional Cancer Center
🇺🇸Walla Walla, Washington, United States
Langlade Hospital and Cancer Center
🇺🇸Antigo, Wisconsin, United States
Marshfield Clinic-Chippewa Center
🇺🇸Chippewa Falls, Wisconsin, United States
Marshfield Medical Center-EC Cancer Center
🇺🇸Eau Claire, Wisconsin, United States
Marshfield Clinic - Ladysmith Center
🇺🇸Ladysmith, Wisconsin, United States
Aspirus Medford Hospital
🇺🇸Medford, Wisconsin, United States
Cancer Center of Western Wisconsin
🇺🇸New Richmond, Wisconsin, United States
Marshfield Medical Center-River Region at Stevens Point
🇺🇸Stevens Point, Wisconsin, United States
Aspirus Regional Cancer Center
🇺🇸Wausau, Wisconsin, United States
Essentia Health Saint Mary's Hospital - Superior
🇺🇸Superior, Wisconsin, United States
Mercy Cancer Center - Sacramento
🇺🇸Sacramento, California, United States
University of California Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
Saint Joseph Mercy Hospital
🇺🇸Ann Arbor, Michigan, United States
Saint Joseph Mercy Chelsea
🇺🇸Chelsea, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
🇺🇸Chelsea, Michigan, United States
Parkland Health Center - Farmington
🇺🇸Farmington, Missouri, United States
Mercy Cancer Center-West Lakes
🇺🇸Clive, Iowa, United States
Saint Mary Corwin Medical Center
🇺🇸Pueblo, Colorado, United States
Holy Cross Hospital
🇺🇸Fort Lauderdale, Florida, United States
Genesys Hurley Cancer Institute
🇺🇸Flint, Michigan, 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
Saint Joseph Mercy Oakland
🇺🇸Pontiac, Michigan, United States
Avera Cancer Institute-Aberdeen
🇺🇸Aberdeen, South Dakota, United States
Saint Louis Cancer and Breast Institute-Ballwin
🇺🇸Ballwin, Missouri, United States
Sanford Medical Center Fargo
🇺🇸Fargo, North Dakota, United States
Prisma Health Cancer Institute - Greer
🇺🇸Greer, South Carolina, United States
Greater Dayton Cancer Center
🇺🇸Kettering, Ohio, United States
Geisinger Wyoming Valley/Henry Cancer Center
🇺🇸Wilkes-Barre, Pennsylvania, United States
Smilow Cancer Hospital Care Center - Westerly
🇺🇸Westerly, Rhode Island, United States
Sanford Cancer Center Oncology Clinic
🇺🇸Sioux Falls, South Dakota, United States
PeaceHealth Southwest Medical Center
🇺🇸Vancouver, Washington, United States
Smilow Cancer Center/Yale-New Haven Hospital
🇺🇸New Haven, Connecticut, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Mercy Hospital Springfield
🇺🇸Springfield, Missouri, United States
Mercy Medical Center - Des Moines
🇺🇸Des Moines, Iowa, United States
Saint Joseph Radiation Oncology Resource Center
🇺🇸Lexington, Kentucky, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Prisma Health Cancer Institute - Eastside
🇺🇸Greenville, South Carolina, United States
21st Century Oncology-Pontiac
🇺🇸Pontiac, Michigan, United States
Fairview Southdale Hospital
🇺🇸Edina, Minnesota, United States
Medical Oncology and Hematology Associates-West Des Moines
🇺🇸Clive, Iowa, United States
Great Lakes Cancer Management Specialists-Van Elslander Cancer Center
🇺🇸Grosse Pointe Woods, Michigan, United States
Carle at The Riverfront
🇺🇸Danville, Illinois, United States
Ascension Saint Mary's Hospital
🇺🇸Rhinelander, Wisconsin, United States
Women's Diagnostic Center - Munster
🇺🇸Munster, Indiana, United States
Southeast Cancer Center
🇺🇸Cape Girardeau, Missouri, United States
Alegent Health Mercy Hospital
🇺🇸Council Bluffs, Iowa, United States
Saint Joseph Mercy Brighton
🇺🇸Brighton, Michigan, United States
Sanford Joe Lueken Cancer Center
🇺🇸Bemidji, Minnesota, United States
Gundersen Lutheran Medical Center
🇺🇸La Crosse, Wisconsin, United States
Hematology Oncology Consultants-Clarkston
🇺🇸Clarkston, Michigan, United States
Ridgeview Medical Center
🇺🇸Waconia, Minnesota, United States
Essentia Health - Moose Lake Clinic
🇺🇸Moose Lake, Minnesota, United States