Multiple Myeloma
Conditions
Keywords
Relapsed, Refractory, Proteasome Inhibitor
Brief summary
The purpose of this study is to evaluate the effect of Ixazomib on inducing osteoblast activation as measured by bone markers and imaging in patients with relapsed/refractory myeloma.
Detailed description
This is a phase II study designed to examine the bone anabolic effect of the next generation proteasome inhibitor, ixazomib, in relapsed/refractory myeloma patients. Treatment consists of Ixazomib 4 mg on days 1, 8, 15, 22 of a 28 day cycle, for a maximum of 6 cycles. Determination of relapsed/refractory disease as an entry criterion may be based on patient data obtained during or following the patient's most recent prior antineoplastic therapy. Treatment periods will be defined as 28-day cycles. Patients will be seen at regular intervals while they are participating in the study.
Interventions
DRUGIxazomib
Sponsors
Millennium Pharmaceuticals, Inc.
University of Arkansas
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Male or female patients 18 years or older. * 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of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.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, AND Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[eg, calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception.) Male patients, even if surgically sterilized (ie, 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 (eg, calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception.) * Patients must have a diagnosis of relapsed/refractory multiple myeloma and must have received at least one line of prior therapy. * Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2. * Patients must meet the following clinical laboratory criteria: Absolute neutrophil count (ANC)1,000/mm3 and platelet count 75,000/mm3. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment. Total bilirubin1.5 the upper limit of the normal range (ULN). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 3 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 (ie, Grade 1 toxicity) from the reversible effects of prior chemotherapy. * Major surgery within 14 days before enrollment. * Radiotherapy within 14 days before enrollment. If the involved field is small (in the opinion of the enrolling investigator), 7 days will be considered a sufficient interval between treatment and administration of the ixazomib. * Patients who have non-myeloma related bone disease that will interfere with the interpretation of the bone-related blood and radiology assessments, including Paget's disease, Rickets, Osteomalacia, and any other metastatic bone cancer. * History of myeloma-related central nervous system 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 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. * Ongoing or active systemic infection, known 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. * Known GI disease or history of 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 non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection. * Patient has Grade 3 peripheral neuropathy, or Grade 2 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 21 days of the start of this trial and throughout the duration of this trial. * Patients who have taken bisphosphonate or RANK Ligand Inhibitor within 3 weeks from screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum Osteocalcin From Baseline to End of Study in Patients With Relapsed/Refractory Multiple Myeloma. | Baseline, Treatment (28-day cycles for 6 cycles) | To evaluate the effect of Ixazomib on inducing osteoblast activation as measured by change in serum osteocalcin from baseline to end of study in patients with relapsed/refractory multiple myeloma. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ixazomib Ixazomib 4.0 mg given on days 1, 8 15, 22 of a 28 day cycle maximum of 6 cycles.
Ixazomib | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Ixazomib |
|---|---|
| Age, Continuous | 70.91 years STANDARD_DEVIATION 10.27 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 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 | 14 Participants |
| Region of Enrollment United States | 20 participants |
| Sex/Gender, Customized Female | 9 participants |
| Sex/Gender, Customized Male | 11 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 15 / 20 |
| other Total, other adverse events | 20 / 20 |
| serious Total, serious adverse events | 8 / 20 |
Outcome results
Primary
Change in Serum Osteocalcin From Baseline to End of Study in Patients With Relapsed/Refractory Multiple Myeloma.
To evaluate the effect of Ixazomib on inducing osteoblast activation as measured by change in serum osteocalcin from baseline to end of study in patients with relapsed/refractory multiple myeloma.
Time frame: Baseline, Treatment (28-day cycles for 6 cycles)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ixazomib | Change in Serum Osteocalcin From Baseline to End of Study in Patients With Relapsed/Refractory Multiple Myeloma. | 20.00 ng/ML |