Ixazomib, Lenalidomide, and Dexamethasone as Consolidation Therapy Followed by Maintenance Ixazomib or Lenalidomide after Stem Cell Transplant in Treating Patients with Multiple Myeloma
This partially randomized phase II trial studies how well ixazomib, lenalidomide, and dexamethasone as consolidation therapy followed by maintenance ixazomib or lenalidomide after stem cell transplant works in treating patients with multiple myeloma. Ixazomib and lenalidomide may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ixazomib with lenalidomide and dexamethasone as consolidation therapy may help prolong the amount of time patients are disease-free after a stem cell transplant. It is not yet known whether giving ixazomib, lenalidomide, and dexamethasone followed by maintenance ixazomib or lenalidomide works better in treating patients with multiple myeloma after a stem cell transplant.
- Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care
- Histologically confirmed diagnosis of symptomatic multiple myeloma; (patients with multiple myeloma with secondary amyloidosis are eligible)
- Received at least two cycles of any regimen as initial systemic therapy for multiple myeloma and are within 2-16 months of the first dose of initial therapy
- Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2
- Absolute neutrophil count (ANC) >= 1,000/mm^3
- Platelet count >= 75,000/mm^3; platelet transfusions to help patients meet eligibility criteria are not allowed within 7 days before study enrollment
- Total bilirubin =< 1.5 x the upper limit of the normal range (ULN)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN
- Calculated creatinine clearance >= 30 mL/min
- Women of childbearing potential must follow pregnancy testing requirements as outlined in the Revlimid Risk Evaluation and Mitigation Strategy (REMS) program material; this is defined as either committing to continued abstinence from heterosexual intercourse or beginning TWO acceptable methods of contraception (one highly effective method and one additional effective method AT THE SAME TIME) at least 28 days prior to the start of lenalidomide, for the duration of study participation, and for 28 days following the last dose of lenalidomide; women of childbearing potential must also agree to ongoing pregnancy testing
- Men must agree to use a latex condom during sexual contact with a woman of childbearing potential even if they have had a successful vasectomy; all patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure; should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately
- All study participants must be registered into the mandatory Revlimid REMS program and be willing to comply with its requirements; per standard Revlimid REMS program requirements, all physicians who prescribe lenalidomide for research subjects enrolled into this trial, must be registered in, and must comply with, all requirements of the Revlimid REMS program
- Female patients who are lactating or have a positive serum pregnancy test during the screening period
- Evidence of MM disease progression any time prior to enrollment; progression from smoldering/asymptomatic MM to symptomatic MM is not exclusionary
- Tandem autologous transplantation
- History of plasma cell leukemia or MM central nervous system (CNS) involvement
- Administration or planned administration of any other concomitant chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy which would be considered a treatment of multiple myeloma until day +28 post-transplant through discontinuation from study; patients may be on corticosteroids if they are being given for disorders other than multiple myeloma (e.g., adrenal insufficiency, rheumatoid arthritis, etc.)
- Any serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol
- Prior organ transplant requiring immunosuppressive therapy
- Active hepatitis A, B, or C virus infection, or known human immunodeficiency virus (HIV) positive
- Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
- Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib
- Concurrent hematologic or non-hematologic malignancy requiring treatment (other than multiple myeloma and secondary amyloidosis)
- Cardiac syncope, uncompensated New York Heart Association (NYHA) class 3 or 4 congestive heart failure, myocardial infarction within the previous 6 months, unstable angina pectoris, clinically significant repetitive ventricular arrhythmias despite antiarrhythmic treatment, severe orthostatic hypotension, or clinically important autonomic disease
- Grade >= 3 peripheral neuropathy, or grade 2 with pain on clinical examination during the screening period
- Major surgery within 14 days prior to start of study treatment
- Infection requiring systemic antibiotic therapy or other serious infection within 14 days prior to start of study treatment
- Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days prior to start of study treatment and throughout the duration of this trial
Locations & Contacts
Trial Objectives and Outline
I. To determine the improvement in minimal residual disease (MRD)-negative rate after 4 cycles of ixazomib, lenalidomide, and dexamethasone (IRD) consolidation.
I. To determine the MRD-negative rate after autologous stem cell transplantation (ASCT).
II. To evaluate the toxicity, response rate, progression-free survival (PFS), and overall survival (OS) of IRD consolidation.
III. To collect pilot data to compare toxicity, response rate, PFS, OS, and the rate of MRD-positive to MRD-negative conversion between the two maintenance arms.
IV. To evaluate the association of PFS and OS with MRD-negativity and MRD-positivity prior to consolidation and after 4 cycles of IRD consolidation.
I. To evaluate the relationship between immunoglobulin heavy/light chain (HEVYLITE) assay results with response and MRD status.
II. To evaluate the effect of ixazomib maintenance on the immune system.
CONSOLIDATION: Approximately 80-120 days after ASCT, patients receive ixazomib orally (PO) and dexamethasone PO on days 1, 8, and 15; and lenalidomide PO daily on days 1-21. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive ixazomib PO on days 1, 8, and 15 every 28 days for up to 3 years in the absence of disease progression or unacceptable toxicity. Patients may crossover to Arm II upon discontinuation of ixazomib if permission is granted by the principal investigator.
ARM II: Patients receive lenalidomide PO daily on days 1-28 every 28 days for up to 3 years in the absence of disease progression or unacceptable toxicity. Patients may crossover to Arm I upon discontinuation of lenalidomide if permission is granted by the principal investigator.
After completion of study treatment, patients are followed up every 3 months for 18 months.
Trial Phase & Type
Siteman Cancer Center at Washington University
Secondary IDs NCI-2014-02210, X16063
Clinicaltrials.gov ID NCT02253316