Ixazomib, Cyclophosphamide and Dexamethasone for Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Ixazomib; Cyclophosphamide; Dexamethasone
Intervention description: Cycle 1:
Ixazomib: 4mg/day 1, 8, 15
Cycles 2-6:
Ixazomib: 4mg/day 1, 4, 8, 11, 15, 18,
Maintenance:
Ixazomib at 4 mg days 1, 8 and 15 of a 28 day cycle for 1 ½ years; Cycle 1:
Cyclophosphamide: 50 mg/day continuous daily
Cycles 2-6:
Cyclophosphamide: 50 mg/day continuous daily; Cycle 1:
Dexamethasone: 20 mg/day 1, 8, 15
Cycles 2-6:
Dexamethasone: 20 mg/day 1, 4, 8, 11, 15, 18
Intervention MeSH terms: Dexamethasone; Cyclophosphamide; Ixazomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The goal of this proposal is to develop a more effective and better tolerated regimen.
      Ixazomib appears to have greater activity than bortezomib with less peripheral neuropathy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥ 18 years of age

          -  Histologically confirmed multiple myeloma according to WHO classification. Pathology
             report to be sent to BrUOG for confirmation

          -  Diagnosis of Multiple Myeloma that has not been previously treated (although patients
             that received emergent steroid and/or local radiation therapy will be permitted to
             enter the study). , Details need to be submitted to BrUOG with dates and doses.

          -  Measureable disease defined as either an elevated serum M-protein, urine M-protein,
             bone marrow involvement >30% or serum free light chains per the IMWG criteria.
             Confirmation to be sent to BrUOG, see section 7 for criteria

          -  Life expectancy of ≥ 6 months, confirmation per treating investigator required

          -  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. If transfusional support provided, please document for
             submission to BrUOG

          -  Calculated creatinine clearance ≥30 mL/min (based on the Cockcroft-Gault Equation
             below)

        For males:

        Creatinine Clearance = (140-age[years] x weight [kg]) 72 x (serum creatinine[mg/dL])

        For females:

        Creatinine Clearance = 0.85 (140-age[years] x weight [kg]) 72 x (serum creatinine[mg/dL])

          -  ECOG performance status of 0-1.

          -  Adequate Liver function; AST or ALT < 3.0 x upper limit of normal (ULN); Total
             bilirubin <1.5x ULN

          -  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 obtain a pregnancy
                  test, which must come back negative prior to drug, OR

               -  Agree to practice true abstinence when this is in line with the preferred and
                  usual lifestyle of the subject and obtain a serum pregnancy test, which must come
                  back negative prior to drug. (Periodic abstinence [eg, calendar, ovulation,
                  symptothermal, post-ovulation methods] and withdrawal are not acceptable methods
                  of contraception.) Documentation and confirmation of conversations and patient
                  commitment to contraception is required to be noted and sent to BrUOG. Female's
                  menopausal status to be documented and submitted to BrUOG if applicable.
                  Pregnancy test, if applicable, required to be sent to BrUOG.

          -  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.) Documentation and confirmation of conversations and patient
                  commitment to contraception is required to be noted and sent to BrUOG.

        Exclusion Criteria:

          -  Female patients who are lactating or have a positive serum pregnancy test during the
             screening period.

          -  Any surgery within 14 days before enrollment.

          -  Radiotherapy within 14 days before enrollment.

          -  Central nervous system involvement (myeloma-related).

          -  Active infection requiring systemic antibiotic therapy or other serious active
             infection within 7 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, 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. If
             not applicable, then investigator to document not applicable

          -  Known allergy to any of the study medications, their analogues, or excipients in the
             various formulations of any agent. If not applicable, then investigator to document
             not applicable

          -  Known GI disease or GI procedure that could interfere with the oral absorption or
             tolerance of ixazomib including difficulty swallowing. If not applicable, then
             investigator to document not applicable

          -  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.

          -  Participation in other therapeutic 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.