Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

Ixazomib, Lenalidomide, and Dexamethasone as Consolidation Therapy Followed by Maintenance Ixazomib or Lenalidomide after Stem Cell Transplant in Treating Patients with Multiple Myeloma

Protocol: OSU-15045

Full Title

A Phase II Study of IRD (Ixazomib, Lenalidomide, & Dexamethasone) for Consolidation Therapy Post Autologous Stem Cell Transplantation followed by Maintenance Ixazomib or Lenalidomide for Multiple Myeloma

Purpose

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.

Study Objective

PRIMARY OBJECTIVES:

I. To determine the improvement in minimal residual disease (MRD)-negative rate after 4 cycles of ixazomib, lenalidomide, and dexamethasone (IRD) consolidation.

SECONDARY OBJECTIVES:

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.

TERTIARY OBJECTIVES:

I. To evaluate the relationship between multiple myeloma (MM) Profiler risk stratification with MRD-negativity prior to consolidation and after 4 cycles of IRD consolidation.

II. To evaluate the relationship between MM Profiler risk stratification PFS, OS, and the rate of MRD-positive to MRD-negative conversion between the two maintenance arms.

III. To evaluate the relationship between immunoglobulin heavy/light chain (HEVYLITE) assay results with response and MRD status.

IV. To investigate the use of mitochondrial profiling as a biomarker in predicting response to IRD consolidation.

OUTLINE:

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.

Are you eligible?

Inclusion Criteria:

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 2-12 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

Exclusion Criteria:

Female patients who are lactating or have a positive serum pregnancy test during the screening period

Evidence of MM disease progression from time of ASCT day 0

History of > 1 prior stem cell transplantation, including 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 from time of ASCT (following neutrophil engraftment) 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

Multiple Myeloma