Testing the Addition of Ixazomib/Placebo to Lenalidomide in Patients With Evidence of Residual Multiple Myeloma, OPTIMUM Trial
Multiple Myeloma
About this trial
This is an interventional treatment trial for Multiple Myeloma
Eligibility Criteria
Inclusion Criteria:
- STEP 0: PRE-REGISTRATION
- Patient must be previously diagnosed with multiple myeloma (MM) and be on lenalidomide maintenance with >= 10mg daily dose (>= 5 mg for patients with creatinine clearance 30-60 mL/min) for at least 10 months and no more than 15 months after an early autologous stem cell transplantation (SCT =< 12 months of diagnosis). Patient must not be off lenalidomide maintenance therapy for more than 30 days prior to start of treatment on Step 1 of this protocol
- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
Patients must be able to undergo a diagnostic bone marrow aspirate following registration to Step 0
- NOTE: A bone marrow aspirate specimen must be submitted to Mayo Clinic Hematology Laboratory for central assessment of minimal residual disease (MRD) status to confirm patient's eligibility for Step 1 randomization. Mayo Clinic will forward results =< within three (3) business days of receipt of the bone marrow specimen to the submitting institution
- Patients must not have primary refractory or progressive disease on a proteasome inhibitor-based regimen during induction therapy prior to stem cell transplant
Patients must not be on other concurrent chemotherapy, or any ancillary therapy considered investigational
- NOTE: Bisphosphonates are considered to be supportive care rather than therapy and are allowed while on protocol treatment
- Patients must not have uncontrolled psychiatric illness or social situations that would limit compliance with study requirements
- Patients must not have another malignancy requiring treatment or have received treatment within 2 years before pre-registration or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
- Patients must have been able to maintain at least 10 mg dose of lenalidomide without growth factor support (at least 5 mg for patients with creatinine clearance 30-60 mL/min)
- Patients must not have known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib or lenalidomide including difficulty swallowing
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
- Patients must not have known hepatitis B surface antigen-positive status or known or suspected active hepatitis C infection, but testing specifically for the trial is not required
- STEP 1 RANDOMIZATION
- Patient must meet Step 0 eligibility criteria at the time of Step 1 randomization
- Patient must not be off lenalidomide maintenance therapy for more than 30 days prior to start of treatment on Step 1 of this protocol
- Patients must have evidence of residual disease by central MRD testing or by presence of monoclonal protein in serum or urine
Serum protein electrophoresis (SPEP), urine protein electrophoresis (UPEP), and serum free light chain (FLC) performed =< 28 days prior to randomization
- NOTE: UPEP (on a 24-hour collection) is required, no substitute method is acceptable. Urine must be followed monthly if the baseline urine M-spike is >= 200 mg/24 hour (hr). Please note that if both serum and urine M-components are present, both must be followed in order to evaluate response
- Hemoglobin >= 8 g/dL (obtained =< 14 days prior to randomization)
- Untransfused platelet count >= 75,000 cells/mm^3 (obtained =< 14 days prior to randomization)
- Absolute neutrophil count >= 1000 cells/mm^3 (obtained =< 14 days prior to randomization)
- Calculated creatinine clearance >= 30 mL/min (obtained =< 14 days prior to randomization)
- Total bilirubin =< 1.5 times the upper limit of normal (obtained =< 14 days prior to randomization)
- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) and serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 3 times the upper limit of normal (obtained =< 14 days prior to randomization)
- Patients must not have grade 2 or higher peripheral neuropathy or grade 1 peripheral neuropathy with pain per CTCAE
- Patients must not have uncontrolled intercurrent illness
- Patients must not have grade 2 or higher diarrhea per CTCAE in the absence of antidiarrheals
- Patients must not have been on systemic treatment, within 14 days before the first dose of ixazomib, with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of St. John's wort
- Patient must agree to register into the mandatory Revlimid Risk Evaluation and Mitigation Strategies (REMS) program and be willing and able to comply with the requirements of Revlimid REMS
- Patient must not be pregnant due to potential harm to the fetus from ixazomib and lenalidomide. All patients of childbearing potential must have a blood test or urine study with a sensitivity of at least 25 mIU/mL within 10-14 days prior to the first dose of lenalidomide and again within 24 hours prior to the first dose of lenalidomide. Patients of childbearing potential must also agree to ongoing pregnancy testing while on treatment. A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
- Patients of childbearing potential must either abstain from sexual intercourse for the duration of their participation in the study or agree to use TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME for 1) at least 28 days before starting study treatment; 2) while participating in the study; 3) during dose interruptions; and 4) for at least 90 days after the last dose of protocol treatment. Patients must also agree to not breastfeed during this same time period. Men must agree to either abstain from sexual intercourse for the duration of their participation in the study or use a latex condom during sexual contact with a partner of childbearing potential while participating in the study and for 90 days after the last dose of protocol treatment even if they have had a successful vasectomy. Patients must also agree to abstain from donating sperm while on study treatment and for 28 days after the last dose of protocol treatment even if they have had a successful vasectomy. All patients must agree to abstain from donating blood during study participation and for at least 28 days after the last dose of protocol treatment
Sites / Locations
- Cancer Center at Saint Joseph's
- CHI Saint Vincent Cancer Center Hot Springs
- Mission Hope Medical Oncology - Arroyo Grande
- Pacific Central Coast Health Center-San Luis Obispo
- Mission Hope Medical Oncology - Santa Maria
- Penrose-Saint Francis Healthcare
- Rocky Mountain Cancer Centers-Penrose
- Porter Adventist Hospital
- Mercy Medical Center
- Southwest Oncology PC
- Saint Anthony Hospital
- Littleton Adventist Hospital
- Longmont United Hospital
- Rocky Mountain Cancer Centers-Longmont
- Parker Adventist Hospital
- Saint Mary Corwin Medical Center
- Rush - Copley Medical Center
- Illinois CancerCare-Bloomington
- Illinois CancerCare-Canton
- Memorial Hospital of Carbondale
- SIH Cancer Institute
- Illinois CancerCare-Carthage
- Centralia Oncology Clinic
- Carle at The Riverfront
- Cancer Care Specialists of Illinois - Decatur
- Decatur Memorial Hospital
- Illinois CancerCare-Dixon
- Carle Physician Group-Effingham
- Crossroads Cancer Center
- Illinois CancerCare-Eureka
- Illinois CancerCare-Galesburg
- Western Illinois Cancer Treatment Center
- Illinois CancerCare-Kewanee Clinic
- Illinois CancerCare-Macomb
- Carle Physician Group-Mattoon/Charleston
- Cancer Care Center of O'Fallon
- Illinois CancerCare-Ottawa Clinic
- Illinois CancerCare-Pekin
- Illinois CancerCare-Peoria
- Methodist Medical Center of Illinois
- Illinois CancerCare-Peru
- Valley Radiation Oncology
- Illinois CancerCare-Princeton
- Southern Illinois University School of Medicine
- Springfield Clinic
- Memorial Medical Center
- Carle Cancer Center
- The Carle Foundation Hospital
- Illinois CancerCare - Washington
- Rush-Copley Healthcare Center
- Mary Greeley Medical Center
- McFarland Clinic - Ames
- McFarland Clinic - Boone
- Saint Anthony Regional Hospital
- Medical Oncology and Hematology Associates-West Des Moines
- Mercy Cancer Center-West Lakes
- Alegent Health Mercy Hospital
- Greater Regional Medical Center
- Iowa Methodist Medical Center
- Medical Oncology and Hematology Associates-Des Moines
- Broadlawns Medical Center
- Mercy Medical Center - Des Moines
- Mission Cancer and Blood - Laurel
- Iowa Lutheran Hospital
- McFarland Clinic - Trinity Cancer Center
- Trinity Regional Medical Center
- McFarland Clinic - Jefferson
- McFarland Clinic - Marshalltown
- Methodist West Hospital
- Mercy Medical Center-West Lakes
- Cancer Center of Kansas-Wichita Medical Arts Tower
- Ascension Via Christi Hospitals Wichita
- Cancer Center of Kansas - Wichita
- Flaget Memorial Hospital
- Commonwealth Cancer Center-Corbin
- Saint Joseph Radiation Oncology Resource Center
- Saint Joseph Hospital East
- Saint Joseph London
- Jewish Hospital
- Saints Mary and Elizabeth Hospital
- UofL Health Medical Center Northeast
- Jewish Hospital Medical Center South
- Tufts Medical Center
- Saint Joseph Mercy Hospital
- University of Michigan Comprehensive Cancer Center
- Bronson Battle Creek
- Saint Joseph Mercy Brighton
- Trinity Health IHA Medical Group Hematology Oncology - Brighton
- Saint Joseph Mercy Canton
- Trinity Health IHA Medical Group Hematology Oncology - Canton
- Saint Joseph Mercy Chelsea
- Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
- Ascension Saint John Hospital
- Great Lakes Cancer Management Specialists-Doctors Park
- Genesee Cancer and Blood Disease Treatment Center
- Genesee Hematology Oncology PC
- Genesys Hurley Cancer Institute
- Spectrum Health at Butterworth Campus
- Trinity Health Grand Rapids Hospital
- Academic Hematology Oncology Specialists
- Great Lakes Cancer Management Specialists-Van Elslander Cancer Center
- Bronson Methodist Hospital
- West Michigan Cancer Center
- Ascension Borgess Cancer Center
- Trinity Health Saint Mary Mercy Livonia Hospital
- Great Lakes Cancer Management Specialists-Macomb Medical Campus
- Trinity Health Muskegon Hospital
- Cancer and Hematology Centers of Western Michigan - Norton Shores
- Spectrum Health Reed City Hospital
- Marie Yeager Cancer Center
- Bhadresh Nayak MD PC-Sterling Heights
- Munson Medical Center
- Great Lakes Cancer Management Specialists-Macomb Professional Building
- Macomb Hematology Oncology PC
- Saint John Macomb-Oakland Hospital
- University of Michigan Health - West
- Huron Gastroenterology PC
- Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
- Sanford Joe Lueken Cancer Center
- Fairview Ridges Hospital
- Minnesota Oncology - Burnsville
- Cambridge Medical Center
- Mercy Hospital
- Fairview Southdale Hospital
- Unity Hospital
- Fairview Clinics and Surgery Center Maple Grove
- Minnesota Oncology Hematology PA-Maplewood
- Saint John's Hospital - Healtheast
- Abbott-Northwestern Hospital
- Hennepin County Medical Center
- Health Partners Inc
- Monticello Cancer Center
- New Ulm Medical Center
- Fairview Northland Medical Center
- North Memorial Medical Health Center
- Mayo Clinic in Rochester
- Park Nicollet Clinic - Saint Louis Park
- Regions Hospital
- United Hospital
- Saint Francis Regional Medical Center
- Lakeview Hospital
- Ridgeview Medical Center
- Rice Memorial Hospital
- Minnesota Oncology Hematology PA-Woodbury
- Fairview Lakes Medical Center
- Saint Francis Medical Center
- Southeast Cancer Center
- Parkland Health Center - Farmington
- Capital Region Southwest Campus
- Missouri Baptist Medical Center
- Mercy Hospital Saint Louis
- Sainte Genevieve County Memorial Hospital
- Missouri Baptist Sullivan Hospital
- Missouri Baptist Outpatient Center-Sunset Hills
- CHI Health Saint Francis
- CHI Health Good Samaritan
- Saint Elizabeth Regional Medical Center
- Alegent Health Immanuel Medical Center
- Alegent Health Bergan Mercy Medical Center
- Alegent Health Lakeside Hospital
- Creighton University Medical Center
- Midlands Community Hospital
- Sanford Bismarck Medical Center
- Sanford Broadway Medical Center
- Sanford Roger Maris Cancer Center
- Strecker Cancer Center-Belpre
- Miami Valley Hospital South
- Adena Regional Medical Center
- Good Samaritan Hospital - Cincinnati
- Bethesda North Hospital
- TriHealth Cancer Institute-Westside
- TriHealth Cancer Institute-Anderson
- Mount Carmel East Hospital
- Columbus Oncology and Hematology Associates Inc
- Riverside Methodist Hospital
- Grant Medical Center
- The Mark H Zangmeister Center
- Mount Carmel Health Center West
- Doctors Hospital
- Miami Valley Hospital
- Miami Valley Hospital North
- Delaware Health Center-Grady Cancer Center
- Grady Memorial Hospital
- Dublin Methodist Hospital
- Atrium Medical Center-Middletown Regional Hospital
- Central Ohio Breast and Endocrine Surgery
- Mount Carmel Grove City Hospital
- Fairfield Medical Center
- Saint Rita's Medical Center
- OhioHealth Mansfield Hospital
- Marietta Memorial Hospital
- OhioHealth Marion General Hospital
- Knox Community Hospital
- Licking Memorial Hospital
- Newark Radiation Oncology
- Mercy Health Perrysburg Cancer Center
- Southern Ohio Medical Center
- Saint Vincent Mercy Medical Center
- Mercy Health - Saint Anne Hospital
- Upper Valley Medical Center
- Saint Ann's Hospital
- Genesis Healthcare System Cancer Care Center
- University of Oklahoma Health Sciences Center
- Oklahoma Cancer Specialists and Research Institute-Tulsa
- Penn State Milton S Hershey Medical Center
- Tidelands Georgetown Memorial Hospital
- Sanford Cancer Center Oncology Clinic
- Sanford USD Medical Center - Sioux Falls
- Saint Joseph Regional Cancer Center
- Harrison Medical Center
- Highline Medical Center-Main Campus
- Saint Elizabeth Hospital
- Saint Francis Hospital
- Saint Clare Hospital
- Franciscan Research Center-Northwest Medical Plaza
- ThedaCare Regional Cancer Center
- ProHealth D N Greenwald Center
- Cancer Center of Western Wisconsin
- ProHealth Oconomowoc Memorial Hospital
- ProHealth Waukesha Memorial Hospital
- UW Cancer Center at ProHealth Care
- Centro Comprensivo de Cancer de UPR
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Arm A (lenalidomide, ixazomib citrate)
Arm B (lenalidomide, placebo)
Patients receive lenalidomide PO QD on days 1-28 and ixazomib citrate PO on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspirate and/or biopsy and PET and CT scan at screening and on study as well as undergo collection of blood samples throughout the trial.
Patients receive lenalidomide PO QD on days 1-28 and a placebo PO on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspirate and/or biopsy and PET and CT scan at screening and on study as well as undergo collection of blood samples throughout the trial.