The purpose of this research study is to evaluate a treatment regimen called IRD which will
be given to participants after their stem cell transplant in an effort to help prolong the
amount of time the participants are disease-free after transplant. IRD is a three-drug
regimen consisting of ixazomib, lenalidomide (also called Revlimid), and dexamethasone.
After 4 cycles of IRD, the participants will be randomized to receive maintenance therapy
either with ixazomib or lenalidomide.
Minimum age: 18 Years.
Maximum age: 70 Years.
Gender(s): Both.
Inclusion Criteria - Pre-ASCT Inclusion Criteria
Each patient must meet all of the following inclusion criteria prior to ASCT to be
screened for the study:
- Between the ages of 18 and 70 years of age (inclusive) at time of enrollment
- 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be withdrawn by the patient at any time without prejudice to future medical care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
Female patients must:
- Be postmenopausal for at least 1 year before the screening visit, OR
- Be surgically sterile, OR
- If 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:
- To practice effective barrier contraception during the entire study treatment period
and through 90 days after the last dose of study drug, OR
- 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.)
Inclusion Criteria to Begin IRD Consolidation - Maintenance Therapy
- Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance
status 0, 1, or 2
- Adequate organ function as defined below:
- Absolute neutrophil count (ANC) ≥ 1,000/mm3
- 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 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 - Pre-ASCT
Patients meeting any of the following exclusion criteria prior to ASCT are not to be
screened for the study:
- Female patients who are lactating or have a positive serum pregnancy test during the
screening period
- Evidence of MM disease progression or relapse at any time prior to enrollment
- Plasma cell leukemia or MM CNS involvement
- Prior stem cell transplant (autologous or allogeneic)
- Prior organ transplant requiring immunosuppressive therapy
- 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.)
- Active hepatitis A, 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
- Known 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 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
Exclusion Criteria to Begin IRD Consolidation - Maintenance Therapy
Patients meeting any of the following exclusion criteria are not to be enrolled in the
study:
- 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
- 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.
- Patient has ≥ 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
- Systemic treatment, within 14 days prior to start of study treatment, with strong
inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of
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
- 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