Cyclophosphamide, Ixazomib, and Dexamethasone in Treating Patients With Previously Untreated Symptomatic Multiple Myeloma

  • Study type:

    Interventional What is this?

    Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • Study phase:

    I/II What is this?

    During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

Study IDs

  • Site IRB:

    • Scottsdale/Phoenix, Arizona: 13-000414
    • Rochester, Minnesota: 13-000414
  • NCT ID:

    NCT01864018
  • Sponsor Protocol Number:

    MC1382

About this study

This phase I/II trial studies the side effects and the best dose of cyclophosphamide when given together with ixazomib and dexamethasone in treating patients with previously untreated symptomatic multiple myeloma. Drugs used in chemotherapy, such as cyclophosphamide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Ixazomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving cyclophosphamide together with ixazomib and dexamethasone may be an effective treatment for multiple myeloma.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

Inclusion Criteria:

  • Calculated creatinine clearance (using Cockcroft-Gault equation) ≥ 30 mL/min
  • Absolute neutrophil count (ANC) ≥ 1000/mm^3
  • Platelet count ≥ 75000/mm^3
  • Hemoglobin ≥ 8.0 g/dL
  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN
  • Prior therapy for the treatment of solitary plasmacytoma is permitted, but > 14 days should have elapsed from the last day of radiation; NOTE: prior therapy with clarithromycin, dehydroepiandrosterone (DHEA), anakinra, pamidronate or zoledronic acid is permitted; any additional agents not listed must be approved by the principal investigator
  • Measurable disease of multiple myeloma as defined by at least ONE of the following:
    • Serum monoclonal protein ≥ 1.0 g/dL
    • > 200 mg of monoclonal protein in the urine on 24 hour electrophoresis
    • Serum immunoglobulin free light chain ≥ 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
  • Previously untreated
  • Provide informed written consent
  • Negative pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only
  • Willing to follow strict birth control measures as suggested by the study
    • Female patients: if they are of childbearing potential, agree to one of the following:
      • 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 must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, 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)
    • 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
      • Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, 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)
  • Willing to return to return to enrolling institution for follow-up (during the active monitoring phase of the study)

Exclusion Criteria:

  • Monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma
  • Prior cytotoxic chemotherapy or corticosteroids for the treatment of multiple myeloma; NOTE: prior corticosteroid use for the treatment of non-malignant disorders is permitted
  • Diagnosed or treated for another malignancy ≤ 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease; NOTE: patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
  • Any of the following:
    • Pregnant women
    • Nursing women
    • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Other co-morbidity which would interfere with patient's ability to participate in trial, e.g. uncontrolled infection, uncompensated heart or lung disease
  • Other concurrent chemotherapy, or any ancillary therapy considered investigational; NOTE: bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment
  • Peripheral neuropathy ≥ grade 3 on clinical examination or grade 2 with pain during the screening period
  • Major surgery ≤14 days prior to study registration
  • Systemic treatment with strong inhibitors of cytochrome P450 1A2 (CYP1A2) (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of cytochrome P450 3A4 (CYP3A4) (clarithromycin, conivaptan, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A4 inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital, Gingko biloba, St. John's wort) ≤ 14 days prior to registration
  • Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, congestive heart failure, unstable angina, or myocardial infarction within the past 6 months; Note: prior to study entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant
  • Radiotherapy ≤ 14 days prior to registration; NOTE: if the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the MLN9708
  • Known human immunodeficiency virus (HIV) positive
  • Known hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection
  • 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
  • Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of MLN9708 including difficulty swallowing
  • Diarrhea > grade 1, based on the National Cancer Institute (NCI) Common Terminology Criteria (CTCAE) grading, in the absence of antidiarrheals
  • Participation in clinical trials with other investigational agents not included in this trial, ≤ 21 days prior to registration

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Shaji Kumar, M.D.

Open for enrollment

Cancer Center Clinical Trials Referral Office

855-776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Shaji Kumar, M.D.

Open for enrollment

Cancer Center Clinical Trials Referral Office

855-776-0015