Comparing Combinations of Drugs to Treat Newly Diagnosed Multiple Myeloma (NDMM) When a Stem Cell Transplant is Not a Medically Suitable Treatment
Plasma Cell Myeloma
About this trial
This is an interventional treatment trial for Plasma Cell Myeloma
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
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.
- 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.
Sites / Locations
- Anchorage Associates in Radiation MedicineRecruiting
- Anchorage Radiation Therapy CenterRecruiting
- Alaska Breast Care and Surgery LLCRecruiting
- Alaska Oncology and Hematology LLCRecruiting
- Alaska Women's Cancer CareRecruiting
- Anchorage Oncology CentreRecruiting
- Katmai Oncology GroupRecruiting
- Providence Alaska Medical CenterRecruiting
- Cancer Center at Saint Joseph'sRecruiting
- Mercy Hospital Fort SmithRecruiting
- CARTI Cancer CenterRecruiting
- John L McClellan Memorial Veterans HospitalRecruiting
- University of Arkansas for Medical SciencesRecruiting
- Mission Hope Medical Oncology - Arroyo GrandeRecruiting
- Providence Saint Joseph Medical Center/Disney Family Cancer CenterRecruiting
- Mercy Cancer Center �� CarmichaelRecruiting
- Mercy San Juan Medical CenterRecruiting
- Mercy Cancer Center - Elk GroveRecruiting
- Fremont - Rideout Cancer CenterRecruiting
- Providence Queen of The ValleyRecruiting
- Mercy Cancer Center - RocklinRecruiting
- Mercy Cancer Center - SacramentoRecruiting
- University of California Davis Comprehensive Cancer CenterRecruiting
- Pacific Central Coast Health Center-San Luis ObispoRecruiting
- Mission Hope Medical Oncology - Santa MariaRecruiting
- Providence Medical Foundation - Santa RosaRecruiting
- Providence Santa Rosa Memorial HospitalRecruiting
- Gene Upshaw Memorial Tahoe Forest Cancer CenterRecruiting
- Woodland Memorial HospitalRecruiting
- Penrose-Saint Francis HealthcareRecruiting
- Rocky Mountain Cancer Centers-PenroseRecruiting
- Saint Francis Cancer CenterRecruiting
- Porter Adventist HospitalRecruiting
- Mercy Medical CenterRecruiting
- Southwest Oncology PCRecruiting
- Saint Anthony HospitalRecruiting
- Littleton Adventist HospitalRecruiting
- Longmont United HospitalRecruiting
- Parker Adventist HospitalRecruiting
- Saint Mary Corwin Medical CenterRecruiting
- Smilow Cancer Hospital-Derby Care CenterRecruiting
- Smilow Cancer Hospital Care Center-FairfieldRecruiting
- Smilow Cancer Hospital Care Center at GlastonburyRecruiting
- Smilow Cancer Hospital Care Center at GreenwichRecruiting
- Smilow Cancer Hospital Care Center - GuilfordRecruiting
- Smilow Cancer Hospital Care Center at Saint FrancisRecruiting
- Smilow Cancer Center/Yale-New Haven HospitalRecruiting
- Yale UniversityRecruiting
- Yale-New Haven Hospital North Haven Medical CenterRecruiting
- Smilow Cancer Hospital Care Center at Long RidgeRecruiting
- Smilow Cancer Hospital-Torrington Care CenterRecruiting
- Smilow Cancer Hospital Care Center-TrumbullRecruiting
- Smilow Cancer Hospital-Waterbury Care CenterRecruiting
- Smilow Cancer Hospital Care Center - WaterfordRecruiting
- Mayo Clinic in FloridaRecruiting
- Jupiter Medical CenterRecruiting
- Saint Luke's Cancer Institute - BoiseRecruiting
- Saint Luke's Cancer Institute - FruitlandRecruiting
- Saint Luke's Cancer Institute - MeridianRecruiting
- Saint Luke's Cancer Institute - NampaRecruiting
- Saint Luke's Cancer Institute - Twin FallsRecruiting
- Saint Anthony's HealthRecruiting
- Rush - Copley Medical CenterRecruiting
- Saint Joseph Medical CenterRecruiting
- Illinois CancerCare-BloomingtonRecruiting
- Loyola Center for Health at Burr RidgeRecruiting
- Illinois CancerCare-CantonRecruiting
- Memorial Hospital of CarbondaleRecruiting
- SIH Cancer InstituteRecruiting
- Illinois CancerCare-CarthageRecruiting
- Centralia Oncology ClinicRecruiting
- Saint Mary's HospitalRecruiting
- Carle at The RiverfrontRecruiting
- Cancer Care Specialists of Illinois - DecaturRecruiting
- Decatur Memorial HospitalRecruiting
- Illinois CancerCare-DixonRecruiting
- Carle Physician Group-EffinghamRecruiting
- Crossroads Cancer CenterRecruiting
- Illinois CancerCare-EurekaRecruiting
- Illinois CancerCare-GalesburgRecruiting
- Western Illinois Cancer Treatment CenterRecruiting
- Loyola Medicine Homer GlenRecruiting
- Illinois CancerCare-Kewanee ClinicRecruiting
- Illinois CancerCare-MacombRecruiting
- Carle Physician Group-Mattoon/CharlestonRecruiting
- Loyola University Medical CenterRecruiting
- Marjorie Weinberg Cancer Center at Loyola-GottliebRecruiting
- Good Samaritan Regional Health CenterRecruiting
- Cancer Care Center of O'FallonRecruiting
- Illinois CancerCare-Ottawa ClinicRecruiting
- Illinois CancerCare-PekinRecruiting
- Illinois CancerCare-PeoriaRecruiting
- Methodist Medical Center of IllinoisRecruiting
- Illinois CancerCare-PeruRecruiting
- Valley Radiation OncologyRecruiting
- Illinois CancerCare-PrincetonRecruiting
- Southern Illinois University School of MedicineRecruiting
- Springfield ClinicRecruiting
- Memorial Medical CenterRecruiting
- Carle Cancer CenterRecruiting
- The Carle Foundation HospitalRecruiting
- Illinois CancerCare - WashingtonRecruiting
- Rush-Copley Healthcare CenterRecruiting
- Physicians' Clinic of Iowa PCRecruiting
- Medical Oncology and Hematology Associates-West Des MoinesRecruiting
- Mercy Cancer Center-West LakesRecruiting
- Alegent Health Mercy HospitalRecruiting
- Greater Regional Medical CenterRecruiting
- Mercy Medical Center - Des MoinesRecruiting
- Mission Cancer and Blood - LaurelRecruiting
- Mercy Medical Center-West LakesRecruiting
- Central Care Cancer Center - Garden CityRecruiting
- Central Care Cancer Center - Great BendRecruiting
- Flaget Memorial HospitalRecruiting
- Commonwealth Cancer Center-CorbinRecruiting
- Saint Joseph HospitalRecruiting
- Saint Joseph Radiation Oncology Resource CenterRecruiting
- Saint Joseph Hospital EastRecruiting
- Saint Joseph LondonRecruiting
- Saint Joseph Mount SterlingRecruiting
- Saint Joseph Mercy HospitalRecruiting
- Saint Joseph Mercy BrightonRecruiting
- Trinity Health IHA Medical Group Hematology Oncology - BrightonRecruiting
- Saint Joseph Mercy CantonRecruiting
- Trinity Health IHA Medical Group Hematology Oncology - CantonRecruiting
- Caro Cancer CenterRecruiting
- Saint Joseph Mercy ChelseaRecruiting
- Trinity Health IHA Medical Group Hematology Oncology - Chelsea HospitalRecruiting
- Hematology Oncology Consultants-ClarkstonRecruiting
- Newland Medical Associates-ClarkstonRecruiting
- Ascension Saint John HospitalRecruiting
- Great Lakes Cancer Management Specialists-Doctors ParkRecruiting
- Genesee Cancer and Blood Disease Treatment CenterRecruiting
- Genesee Hematology Oncology PCRecruiting
- Genesys Hurley Cancer InstituteRecruiting
- Hurley Medical CenterRecruiting
- Academic Hematology Oncology SpecialistsRecruiting
- Great Lakes Cancer Management Specialists-Van Elslander Cancer CenterRecruiting
- Sparrow HospitalRecruiting
- Trinity Health Saint Mary Mercy Livonia HospitalRecruiting
- Great Lakes Cancer Management Specialists-Macomb Medical CampusRecruiting
- Saint Mary's Oncology/Hematology Associates of MarletteRecruiting
- 21st Century Oncology-PontiacRecruiting
- Hope Cancer CenterRecruiting
- Newland Medical Associates-PontiacRecruiting
- Saint Joseph Mercy OaklandRecruiting
- Ascension Saint Mary's HospitalRecruiting
- Oncology Hematology Associates of Saginaw Valley PCRecruiting
- Bhadresh Nayak MD PC-Sterling HeightsRecruiting
- Ascension Saint Joseph HospitalRecruiting
- Advanced Breast Care Center PLLCRecruiting
- Great Lakes Cancer Management Specialists-Macomb Professional BuildingRecruiting
- Macomb Hematology Oncology PCRecruiting
- Michigan Breast Specialists-WarrenRecruiting
- Saint John Macomb-Oakland HospitalRecruiting
- Saint Mary's Oncology/Hematology Associates of West BranchRecruiting
- Huron Gastroenterology PCRecruiting
- Trinity Health IHA Medical Group Hematology Oncology Ann Arbor CampusRecruiting
- Sanford Joe Lueken Cancer CenterRecruiting
- Minnesota Oncology - BurnsvilleRecruiting
- Cambridge Medical CenterRecruiting
- Mercy HospitalRecruiting
- Fairview Southdale HospitalRecruiting
- Unity Hospital
- Fairview Clinics and Surgery Center Maple GroveRecruiting
- Minnesota Oncology Hematology PA-MaplewoodRecruiting
- Saint John's Hospital - HealtheastRecruiting
- Abbott-Northwestern HospitalRecruiting
- Hennepin County Medical CenterRecruiting
- Health Partners IncRecruiting
- Monticello Cancer CenterRecruiting
- New Ulm Medical CenterRecruiting
- Fairview Northland Medical CenterRecruiting
- North Memorial Medical Health CenterRecruiting
- Mayo Clinic in RochesterRecruiting
- Park Nicollet Clinic - Saint Louis ParkRecruiting
- Regions HospitalRecruiting
- United HospitalRecruiting
- Saint Francis Regional Medical CenterRecruiting
- Lakeview HospitalRecruiting
- Sanford Thief River Falls Medical CenterRecruiting
- Ridgeview Medical CenterRecruiting
- Rice Memorial HospitalRecruiting
- Minnesota Oncology Hematology PA-WoodburyRecruiting
- Sanford Cancer Center WorthingtonRecruiting
- Fairview Lakes Medical CenterRecruiting
- Saint Louis Cancer and Breast Institute-BallwinRecruiting
- Central Care Cancer Center - BolivarRecruiting
- Cox Cancer Center BransonRecruiting
- Saint Francis Medical CenterRecruiting
- Southeast Cancer CenterRecruiting
- Parkland Health Center - FarmingtonRecruiting
- Capital Region Southwest CampusRecruiting
- Freeman Health SystemRecruiting
- Mercy Hospital JoplinRecruiting
- Lake Regional HospitalRecruiting
- Delbert Day Cancer Institute at PCRMCRecruiting
- Mercy Clinic-Rolla-Cancer and HematologyRecruiting
- Heartland Regional Medical CenterRecruiting
- Saint Louis Cancer and Breast Institute-South CityRecruiting
- Mercy Hospital SouthRecruiting
- Missouri Baptist Medical CenterRecruiting
- Mercy Hospital Saint LouisRecruiting
- Sainte Genevieve County Memorial HospitalRecruiting
- Mercy Hospital SpringfieldRecruiting
- CoxHealth South HospitalRecruiting
- Missouri Baptist Sullivan HospitalRecruiting
- Missouri Baptist Outpatient Center-Sunset HillsRecruiting
- Mercy Hospital WashingtonRecruiting
- Saint Patrick Hospital - Community HospitalRecruiting
- CHI Health Good SamaritanRecruiting
- Saint Elizabeth Regional Medical CenterRecruiting
- Alegent Health Immanuel Medical CenterRecruiting
- Alegent Health Bergan Mercy Medical CenterRecruiting
- Alegent Health Lakeside HospitalRecruiting
- Creighton University Medical CenterRecruiting
- Midlands Community HospitalRecruiting
- University of New Mexico Cancer CenterRecruiting
- University of RochesterRecruiting
- Sanford Bismarck Medical CenterRecruiting
- Sanford South University Medical CenterRecruiting
- Southpointe-Sanford Medical Center FargoRecruiting
- Sanford Medical Center FargoRecruiting
- Sanford Broadway Medical CenterRecruiting
- Sanford Roger Maris Cancer CenterRecruiting
- Good Samaritan Hospital - CincinnatiRecruiting
- Bethesda North HospitalRecruiting
- TriHealth Cancer Institute-WestsideRecruiting
- TriHealth Cancer Institute-AndersonRecruiting
- University of Oklahoma Health Sciences Center
- Mercy Hospital Oklahoma CityRecruiting
- Saint Charles Health SystemRecruiting
- Clackamas Radiation Oncology CenterRecruiting
- Providence Cancer Institute Clackamas ClinicRecruiting
- Bay Area HospitalRecruiting
- Providence Newberg Medical CenterRecruiting
- Providence Willamette Falls Medical CenterRecruiting
- Providence Portland Medical CenterRecruiting
- Providence Saint Vincent Medical CenterRecruiting
- Saint Charles Health System-RedmondRecruiting
- Lehigh Valley Hospital-Cedar CrestRecruiting
- Lehigh Valley Hospital - MuhlenbergRecruiting
- Pocono Medical CenterRecruiting
- Lehigh Valley Hospital-HazletonRecruiting
- Smilow Cancer Hospital Care Center - WesterlyRecruiting
- Prisma Health Cancer Institute - SpartanburgRecruiting
- Prisma Health Cancer Institute - EasleyRecruiting
- Prisma Health Cancer Institute - ButternutRecruiting
- Prisma Health Cancer Institute - FarisRecruiting
- Prisma Health Cancer Institute - EastsideRecruiting
- Prisma Health Cancer Institute - GreerRecruiting
- Prisma Health Cancer Institute - SenecaRecruiting
- Avera Cancer Institute-AberdeenRecruiting
- Sanford Cancer Center Oncology ClinicRecruiting
- Avera Cancer InstituteRecruiting
- Sanford USD Medical Center - Sioux FallsRecruiting
- Avera Cancer Institute at YanktonRecruiting
- Sovah Health MartinsvilleRecruiting
- Providence Regional Cancer System-AberdeenRecruiting
- PeaceHealth Saint Joseph Medical CenterRecruiting
- Harrison Medical CenterRecruiting
- Providence Regional Cancer System-CentraliaRecruiting
- Swedish Cancer Institute-EdmondsRecruiting
- Providence Regional Cancer PartnershipRecruiting
- Swedish Cancer Institute-IssaquahRecruiting
- Kadlec Clinic Hematology and OncologyRecruiting
- Providence Regional Cancer System-LaceyRecruiting
- PeaceHealth Saint John Medical CenterRecruiting
- Swedish Medical Center-Ballard CampusRecruiting
- Swedish Medical Center-Cherry HillRecruiting
- Swedish Medical Center-First HillRecruiting
- PeaceHealth United General Medical CenterRecruiting
- Providence Regional Cancer System-SheltonRecruiting
- PeaceHealth Southwest Medical CenterRecruiting
- Providence Saint Mary Regional Cancer CenterRecruiting
- Providence Regional Cancer System-YelmRecruiting
- ThedaCare Regional Cancer CenterRecruiting
- Gundersen Lutheran Medical CenterRecruiting
- Cancer Center of Western WisconsinRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Active Comparator
Experimental
Experimental
Arm I (VRd-Lite)
Arm II (DRd-R)
Arm III (DRd-DR):
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.
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.
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.