Multiple Myeloma Clinical Trial
Testing the Addition of Ixazomib/Placebo to Lenalidomide in Patients With Evidence of Residual Multiple Myeloma, OPTIMUM Trial
Summary
This phase III trial studies how well lenalidomide in combination with ixazomib works compared to lenalidomide alone in treating patients with evidence of residual multiple myeloma after stem cell transplantation. Lenalidomide may help shrink or slow the growth of multiple myeloma. Ixazomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving lenalidomide and ixazomib together may work better than giving lenalidomide alone in treating patients with evidence of residual multiple myeloma after a stem cell transplantation.
Full Description
PRIMARY OBJECTIVE:
I. To evaluate whether escalating maintenance therapy with the addition of ixazomib citrate (ixazomib) to lenalidomide improves overall survival (OS) among patients who are minimal residual disease (MRD) positive after approximately 1 year of lenalidomide maintenance following an early stem cell transplant (=< 12 months from diagnosis).
SECONDARY OBJECTIVES:
I. To establish whether progression-free survival (PFS) is superior with the addition of ixazomib to lenalidomide maintenance.
II. To evaluate best response on treatment and compare response rates between arms.
III. To evaluate the safety profile of ixazomib added to lenalidomide and compare toxicity rates between arms.
EXPLORATORY OBJECTIVES:
I. To measure treatment exposure and adherence. II. To estimate treatment duration, duration of response and time to progression.
PATIENT-REPORTED OUTCOMES (PRO) OBJECTIVES:
I. To quantify the extent to which the addition of ixazomib to lenalidomide maintenance contributes to neuropathy and associated physical and functional impairments. (Primary) II. To assess the impact of the addition of ixazomib to lenalidomide maintenance on disease control and associated physical and functional well-being. (Primary) III. To evaluate time to worsening and recovery rate related to neuropathy. (Secondary) IV. To evaluate time to improvement and response rate related to disease control. (Secondary) V. To evaluate attributes of select patient reported treatment-emergent symptomatic adverse events (Patient-Reported Outcomes - Common Terminology Criteria for Adverse Events [PRO-CTCAE]) longitudinally and compare responses with provider-reported adverse events. (Exploratory) VI. To measure the likelihood of medication adherence and examine the relationship with treatment exposure. (Exploratory) VII. To assess correlation among patient reported outcome measures and association with clinical outcomes. (Exploratory) VIII. To tabulate PRO compliance and completion rates. (Exploratory)
IMAGING OBJECTIVES:
I. To evaluate the association between baseline fludeoxyglucose F-18 (18F-FDG)-positron emission tomography (PET)/computed tomography (CT) and patient outcomes.
II. To compare overall survival (OS) with the addition of ixazomib to lenalidomide among baseline 18F-FDG PET/CT-positive and 18F-FDG PET/CT -negative subgroups.
III. To compare the change in quantitative 18F-FDG PET/CT parameters over time with the addition of ixazomib to lenalidomide.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive lenalidomide orally (PO) once daily (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 positron emission tomography (PET) and computed tomography (CT) scan at screening and on study as well as undergo collection of blood samples throughout the trial.
ARM B: 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.
After completion of study treatment, patients are followed up every 3 months if < 2 years from study entry, every 6 months if 2-5 years from study entry, then every 12 months for up to 10 years from study entry.
Eligibility Criteria
Inclusion Criteria:
STEP 0: PRE-REGISTRATION
Patient must be >= 18 years of age
Patient must be previously diagnosed with multiple myeloma (MM) and be on lenalidomide maintenance with >= 5mg daily for at least 6 months and no more than 18 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
Patient must be able to undergo a diagnostic bone marrow aspirate following pre-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 to the submitting institution within three (3) business days of receipt of the bone marrow specimen
Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
Patient must have been able to maintain at least 5mg daily dose of lenalidomide without growth factor support
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
STEP 1 RANDOMIZATION
Patient must meet Step 0 eligibility criteria at the time of Step 1 randomization
Patients must have evidence of residual disease by central MRD testing or by presence of monoclonal protein in serum or urine
Patient must have 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 (ANC) >= 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 (ULN) (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 (ULN) (obtained =< 14 days prior to randomization)
Patient must agree to register into the mandatory Revlimid Risk Evaluation and Mitigation Strategies (REMS) registered trademark program and be willing and able to comply with the requirements of Revlimid REMS registered trademark
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
Exclusion Criteria:
Patient must not have primary refractory or progressive disease on a proteasome inhibitor-based regimen during induction therapy prior to stem cell transplant
Patient 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
Patient must not have uncontrolled psychiatric illness or social situations that would limit compliance with study requirements
Patient must not have another malignancy requiring treatment or have received treatment within two 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 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
Patient 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
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 not have grade 2 or higher peripheral neuropathy or grade 1 peripheral neuropathy with pain per Common Terminology Criteria for Adverse Events (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 (such as rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of St. John's wort
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)
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There are 185 Locations for this study
Phoenix Arizona, 85004, United States
Hot Springs Arkansas, 71913, United States
Arroyo Grande California, 93420, United States
San Luis Obispo California, 93401, United States
Santa Maria California, 93444, United States
Colorado Springs Colorado, 80907, United States
Colorado Springs Colorado, 80907, United States
Denver Colorado, 80210, United States
Durango Colorado, 81301, United States
Durango Colorado, 81301, United States
Lakewood Colorado, 80228, United States
Littleton Colorado, 80122, United States
Longmont Colorado, 80501, United States
Longmont Colorado, 80501, United States
Parker Colorado, 80138, United States
Pueblo Colorado, 81004, United States
Aurora Illinois, 60504, United States
Bloomington Illinois, 61704, United States
Canton Illinois, 61520, United States
Carbondale Illinois, 62902, United States
Carterville Illinois, 62918, United States
Carthage Illinois, 62321, United States
Centralia Illinois, 62801, United States
Danville Illinois, 61832, United States
Decatur Illinois, 62526, United States
Decatur Illinois, 62526, United States
Dixon Illinois, 61021, United States
Effingham Illinois, 62401, United States
Effingham Illinois, 62401, United States
Eureka Illinois, 61530, United States
Galesburg Illinois, 61401, United States
Galesburg Illinois, 61401, United States
Kewanee Illinois, 61443, United States
Macomb Illinois, 61455, United States
Mattoon Illinois, 61938, United States
O'Fallon Illinois, 62269, United States
Ottawa Illinois, 61350, United States
Pekin Illinois, 61554, United States
Peoria Illinois, 61615, United States
Peoria Illinois, 61636, United States
Peru Illinois, 61354, United States
Peru Illinois, 61354, United States
Princeton Illinois, 61356, United States
Springfield Illinois, 62702, United States
Springfield Illinois, 62702, United States
Springfield Illinois, 62781, United States
Urbana Illinois, 61801, United States
Urbana Illinois, 61801, United States
Washington Illinois, 61571, United States
Yorkville Illinois, 60560, United States
Ames Iowa, 50010, United States
Ames Iowa, 50010, United States
Boone Iowa, 50036, United States
Carroll Iowa, 51401, United States
Clive Iowa, 50325, United States
Clive Iowa, 50325, United States
Council Bluffs Iowa, 51503, United States
Creston Iowa, 50801, United States
Des Moines Iowa, 50309, United States
Des Moines Iowa, 50309, United States
Des Moines Iowa, 50314, United States
Des Moines Iowa, 50314, United States
Des Moines Iowa, 50314, United States
Des Moines Iowa, 50316, United States
Fort Dodge Iowa, 50501, United States
Fort Dodge Iowa, 50501, United States
Jefferson Iowa, 50129, United States
Marshalltown Iowa, 50158, United States
West Des Moines Iowa, 50266, United States
West Des Moines Iowa, 50266, United States
Wichita Kansas, 67208, United States
Wichita Kansas, 67214, United States
Wichita Kansas, 67214, United States
Bardstown Kentucky, 40004, United States
Corbin Kentucky, 40701, United States
Lexington Kentucky, 40504, United States
Lexington Kentucky, 40509, United States
London Kentucky, 40741, United States
Louisville Kentucky, 40202, United States
Louisville Kentucky, 40215, United States
Louisville Kentucky, 40245, United States
Shepherdsville Kentucky, 40165, United States
Boston Massachusetts, 02111, United States
Ann Arbor Michigan, 48106, United States
Ann Arbor Michigan, 48109, United States
Battle Creek Michigan, 49017, United States
Brighton Michigan, 48114, United States
Brighton Michigan, 48114, United States
Canton Michigan, 48188, United States
Canton Michigan, 48188, United States
Chelsea Michigan, 48118, United States
Chelsea Michigan, 48118, United States
Detroit Michigan, 48236, United States
East China Township Michigan, 48054, United States
Flint Michigan, 48503, United States
Flint Michigan, 48503, United States
Flint Michigan, 48503, United States
Grand Rapids Michigan, 49503, United States
Grand Rapids Michigan, 49503, United States
Grosse Pointe Woods Michigan, 48236, United States
Grosse Pointe Woods Michigan, 48236, United States
Kalamazoo Michigan, 49007, United States
Kalamazoo Michigan, 49007, United States
Kalamazoo Michigan, 49009, United States
Livonia Michigan, 48154, United States
Macomb Michigan, 48044, United States
Muskegon Michigan, 49444, United States
Norton Shores Michigan, 49444, United States
Reed City Michigan, 49677, United States
Saint Joseph Michigan, 49085, United States
Sterling Heights Michigan, 48312, United States
Traverse City Michigan, 49684, United States
Warren Michigan, 48093, United States
Warren Michigan, 48093, United States
Warren Michigan, 48093, United States
Wyoming Michigan, 49519, United States
Ypsilanti Michigan, 48106, United States
Ypsilanti Michigan, 48197, United States
Bemidji Minnesota, 56601, United States
Burnsville Minnesota, 55337, United States
Burnsville Minnesota, 55337, United States
Cambridge Minnesota, 55008, United States
Coon Rapids Minnesota, 55433, United States
Edina Minnesota, 55435, United States
Fridley Minnesota, 55432, United States
Maple Grove Minnesota, 55369, United States
Maplewood Minnesota, 55109, United States
Maplewood Minnesota, 55109, United States
Minneapolis Minnesota, 55407, United States
Minneapolis Minnesota, 55415, United States
Minneapolis Minnesota, 55454, United States
Monticello Minnesota, 55362, United States
New Ulm Minnesota, 56073, United States
Princeton Minnesota, 55371, United States
Robbinsdale Minnesota, 55422, United States
Rochester Minnesota, 55905, United States
Saint Louis Park Minnesota, 55416, United States
Saint Paul Minnesota, 55101, United States
Saint Paul Minnesota, 55102, United States
Shakopee Minnesota, 55379, United States
Stillwater Minnesota, 55082, United States
Waconia Minnesota, 55387, United States
Willmar Minnesota, 56201, United States
Woodbury Minnesota, 55125, United States
Wyoming Minnesota, 55092, United States
Cape Girardeau Missouri, 63703, United States
Cape Girardeau Missouri, 63703, United States
Farmington Missouri, 63640, United States
Jefferson City Missouri, 65109, United States
Saint Louis Missouri, 63131, United States
Saint Louis Missouri, 63141, United States
Sainte Genevieve Missouri, 63670, United States
Sullivan Missouri, 63080, United States
Sunset Hills Missouri, 63127, United States
Grand Island Nebraska, 68803, United States
Kearney Nebraska, 68847, United States
Lincoln Nebraska, 68510, United States
Omaha Nebraska, 68122, United States
Omaha Nebraska, 68124, United States
Omaha Nebraska, 68130, United States
Omaha Nebraska, 68131, United States
Papillion Nebraska, 68046, United States
Bismarck North Dakota, 58501, United States
Fargo North Dakota, 58122, United States
Fargo North Dakota, 58122, United States
Belpre Ohio, 45714, United States
Centerville Ohio, 45459, United States
Chillicothe Ohio, 45601, United States
Cincinnati Ohio, 45220, United States
Cincinnati Ohio, 45242, United States
Cincinnati Ohio, 45247, United States
Cincinnati Ohio, 45255, United States
Columbus Ohio, 43213, United States
Columbus Ohio, 43214, United States
Columbus Ohio, 43214, United States
Columbus Ohio, 43215, United States
Columbus Ohio, 43219, United States
Columbus Ohio, 43222, United States
Columbus Ohio, 43228, United States
Dayton Ohio, 45409, United States
Dayton Ohio, 45415, United States
Delaware Ohio, 43015, United States
Delaware Ohio, 43015, United States
Dublin Ohio, 43016, United States
Franklin Ohio, 45005, United States
Gahanna Ohio, 43230, United States
Grove City Ohio, 43123, United States
Lancaster Ohio, 43130, United States
Lima Ohio, 45801, United States
Mansfield Ohio, 44903, United States
Marietta Ohio, 45750, United States
Marion Ohio, 43302, United States
Mount Vernon Ohio, 43050, United States
Newark Ohio, 43055, United States
Newark Ohio, 43055, United States
Perrysburg Ohio, 43551, United States
Portsmouth Ohio, 45662, United States
Toledo Ohio, 43608, United States
Toledo Ohio, 43623, United States
Troy Ohio, 45373, United States
Westerville Ohio, 43081, United States
Zanesville Ohio, 43701, United States
Oklahoma City Oklahoma, 73104, United States
Tulsa Oklahoma, 74146, United States
Hershey Pennsylvania, 17033, United States
Georgetown South Carolina, 29440, United States
Sioux Falls South Dakota, 57104, United States
Sioux Falls South Dakota, 57117, United States
Bryan Texas, 77802, United States
Bremerton Washington, 98310, United States
Burien Washington, 98166, United States
Enumclaw Washington, 98022, United States
Federal Way Washington, 98003, United States
Lakewood Washington, 98499, United States
Tacoma Washington, 98405, United States
Appleton Wisconsin, 54911, United States
La Crosse Wisconsin, 54601, United States
Mukwonago Wisconsin, 53149, United States
New Richmond Wisconsin, 54017, United States
Oconomowoc Wisconsin, 53066, United States
Waukesha Wisconsin, 53188, United States
Waukesha Wisconsin, 53188, United States
San Juan , 00927, Puerto Rico
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