UARK 2014-14: Phase II Prospective Evaluation of Bone Remodeling During Ixazomib Treatment
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Ixazomib
Intervention MeSH terms: Ixazomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Relapsed; Refractory; Proteasome Inhibitor

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.
    

Eligibility criteria:

        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             be withdrawn by the patient at any time without prejudice to future medical care.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.