PRIMARY OBJECTIVES:
I. Evaluate the toxicity of the use of ixazomib (ixazomib citrate) and lenalidomide as
maintenance therapy after autologous transplant.
SECONDARY OBJECTIVES:
I. Evaluate the ability to deliver the planned therapy.
II. Assess initial response to therapy.
III. Evaluate the median time to disease progression.
IV. Assess overall survival.
OUTLINE:
Within 30-120 days after completion of autologous transplant, patients receive ixazomib
citrate orally (PO) on days 1, 8 and 15 every 28 days for 2 courses, followed by lenalidomide
PO once daily (QD) on days 1-28 for 2 courses. Treatment repeats, alternating after every 2
courses, for up to 24 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 3
months for 2 years.
Inclusion Criteria:
- Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance
status 0, 1, or 2
- Any autologous patient who underwent high dose melphalan (>= 140 mg/m^2)
therapy/peripheral blood stem cell (PBSC) rescue for any stage of multiple myeloma and
did not participate in another clinical transplant trial whose primary endpoint is
also evaluating long-term, disease-free survival or survival; consenting for study
between 30 days to 120 days after transplant; earliest can start therapy is 30 days
post transplant after recovered from acute toxicity of autologous stem cell transplant
(ASCT)
- 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be withdrawn by the patient at any time without prejudice to future medical care
- Female patients who:
- Are postmenopausal for at least 1 year before the screening visit, OR
- Are surgically sterile, OR
- If they are of childbearing potential, agree to practice 2 effective methods of
contraception, at the same time, from the time of signing the informed consent
form through 90 days after the last dose of study drug, OR
- Agree to practice true abstinence when this is in line with the preferred and
usual lifestyle of the subject; (periodic abstinence [e.g., calendar, ovulation,
symptothermal, post-ovulation methods] and withdrawal are not acceptable methods
of contraception)
- Male patients, even if surgically sterilized (i.e., status post-vasectomy), must agree
to one of the following:
- Agree to practice effective barrier contraception during the entire study
treatment period and through 90 days after the last dose of study drug, OR
- Agree to practice true abstinence when this is in line with the preferred and
usual lifestyle of the subject; (periodic abstinence [e.g., calendar, ovulation,
symptothermal, post-ovulation methods] and withdrawal are not acceptable methods
of contraception)
- Absolute neutrophil count (ANC) >= 1,000/mm^3
- Platelet count (transfusion independent) >= 75,000/mm^3
- 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
Exclusion Criteria:
- Female patients who are lactating or have a positive serum pregnancy test during the
screening period
- Failure to have fully recovered (i.e., =< grade 1 toxicity) from the reversible
effects of prior ASCT chemotherapy
- Major surgery within 14 days before enrollment
- Radiotherapy within 14 days before enrollment; if the involved field is small, 7 days
will be considered a sufficient interval between treatment and administration of the
ixazomib
- History of central nervous system multiple myeloma involvement
- Infection requiring systemic antibiotic therapy or other serious infection within 14
days before study enrollment
- Evidence of current uncontrolled cardiovascular conditions, including uncontrolled
hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure,
unstable angina, or myocardial infarction within the past 6 months
- Systemic treatment, within 14 days before the first dose of ixazomib, with strong
inhibitors of cytochrome P450, family 1, subfamily A, polypeptide 2 gene (CYP1A2)
(fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of cytochrome P450, family
3, subfamily A gene locus (CYP3A) (clarithromycin, telithromycin, itraconazole,
voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers
(rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of
Ginkgo biloba or St. John's wort
- Ongoing or active systemic infection, active hepatitis B or C virus infection, or
known human immunodeficiency virus (HIV) positive
- Any serious medical or psychiatric illness that could, in the investigator's opinion,
potentially interfere with the completion of treatment according to this protocol
- Known allergy to any of the study medications, their analogues, or excipients in the
various formulations of any agent; patient cannot be allergic to boron
- Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral
absorption or tolerance of ixazomib including difficulty swallowing
- Diagnosed or treated for another malignancy within 2 years before study enrollment or
previously diagnosed with another malignancy and have any evidence of residual
disease; patients with nonmelanoma skin cancer or carcinoma in situ of any type are
not excluded if they have undergone complete resection
- Patient has >= grade 2 peripheral neuropathy, or grade 1 with pain on clinical
examination during the screening period
- Participation in other clinical trials, including those with other investigational
agents not included in this trial, within 30 days of the start of this trial and
throughout the duration of this trial
- Patients with history prior to transplant of progression on lenalidomide therapy
