Plasma Cell Myeloma, Transplant-Related Carcinoma
Conditions
Brief summary
This phase II trial studies the safety of alternating ixazomib citrate and lenalidomide as treatment to help keep cancer from coming back after stem cell transplant (maintenance therapy) in treating patients with multiple myeloma. Ixazomib citrate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lenalidomide may stimulate the immune system to attack cancer cells. Giving ixazomib citrate and lenalidomide as maintenance therapy after transplant may prolong the length of time until the cancer returns.
Detailed description
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.
Interventions
DRUGIxazomib Citrate
Given PO
OTHERLaboratory Biomarker Analysis
Correlative studies
DRUGLenalidomide
Given PO
Sponsors
Fred Hutchinson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events, Graded According to CTCAE Version 4.0 | 2 years plus one month | Adverse events Toxicity during the 24 months plus one month of post autologous transplant maintenance therapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Free Survival | Median of 4.6 years from start of study therapy | — |
| Overall Survival | Median 4.6 years from start of therapy | all MM patients who got post autologous transplant study therapy |
Countries
United States
Participant flow
Pre-assignment details
all patients enrolled on study were treated on study
Participants by arm
| Arm | Count |
|---|---|
| Post Autologous Transplant Maintenance one treatment arm all patients enrolled on study | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of Efficacy | 8 |
| Overall Study | new secondary cancer | 1 |
| Overall Study | post surgery complications | 2 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Post Autologous Transplant Maintenance |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 8 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| number of participants treated | 30 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 27 Participants |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 9 / 30 |
| other Total, other adverse events | 30 / 30 |
| serious Total, serious adverse events | 4 / 30 |
Outcome results
Primary
Number of Participants With Adverse Events, Graded According to CTCAE Version 4.0
Adverse events Toxicity during the 24 months plus one month of post autologous transplant maintenance therapy
Time frame: 2 years plus one month
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Post Autologous Transplant Maintenance | Number of Participants With Adverse Events, Graded According to CTCAE Version 4.0 | 30 Participants |
Secondary
Disease Free Survival
Time frame: Median of 4.6 years from start of study therapy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Post Autologous Transplant Maintenance | Disease Free Survival | 11 Participants |
Secondary
Overall Survival
all MM patients who got post autologous transplant study therapy
Time frame: Median 4.6 years from start of therapy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Post Autologous Transplant Maintenance | Overall Survival | 21 Participants |