Proteasome Inhibitor MLN9708 in Treating Patients with Relapsed Multiple Myeloma that is not Refractory to Bortezomib

  • 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:

    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: 11-001516
    • Jacksonville, Florida: 11-001516
    • Rochester, Minnesota: 11-001516
  • NCT ID:

    NCT01415882
  • Sponsor Protocol Number:

    MC1181

About this study

This phase II trial studies how well proteasome inhibitor MLN9708 works in treating patients with relapsed multiple myeloma that is not refractory to bortezomib. Proteasome inhibitor MLN9708 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

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 ≥ 1000/mL
  • Untransfused platelet count ≥ 75000/mL
  • Hemoglobin ≥ 8.0 g/dL
  • Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN)
  • Aspartate aminotransferase (AST) ≤ 3 x ULN
  • Patients with relapsed multiple myeloma who have already received one or more standard treatment regimens
  • 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, 2
  • Patients should be proteasome inhibitor naïve (including bortezomib) OR have received less than 6 cycles of therapy with a bortezomib containing regimen and were not refractory to the bortezomib based regimen (less than a PR or progression on or within 60 days of discontinuation)
  • Provide informed written consent
  • Negative pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only
  • Willing to return to Mayo Clinic institution for follow-up during the Active Monitoring Phase of the study; Note: during the Active Monitoring Phase of a study (i.e., active treatment and observation), participants must be willing to return to the consenting institution for follow-up
  • Recovered (ie, < grade 1 toxicity) from the reversible effects of prior antineoplastic therapy

Exclusion Criteria:

  • Recent prior chemotherapy:
    • Alkylators (e.g. melphalan, cyclophosphamide) =< 14 days prior to registration
    • Anthracyclines =< 14 days prior to registration
    • High dose corticosteroids, immune modulatory drugs (thalidomide or lenalidomide) =< 7 days prior to registration
  • Prior therapy with any proteasome inhibitor other than bortezomib
  • Concomitant high dose corticosteroids other than what is part of treatment protocol (concurrent use of corticosteroids); EXCEPTION: patients may be on chronic steroids (maximum dose 20 mg/day prednisone equivalent) if they are being given for disorders other than myeloma, i.e., adrenal insufficiency, rheumatoid arthritis, etc
  • 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
  • Any of the following:
    • Pregnant women or women of reproductive ability who are unwilling to use 2 effective methods of contraception from the time of signing the informed consent form through 90 days after the last dose of study drug
    • Nursing women
    • Men who are unwilling to use a condom (even if they have undergone prior vasectomy) while having intercourse with any women, while taking the drug and for 30 days after stopping treatment
  • 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, radiotherapy, 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
  • Patient has ≥ grade 3 peripheral neuropathy, or grade 2 with pain on clinical examination during the screening period
  • Major surgery within 14 days before study registration
  • Systemic treatment with strong inhibitors of cytochrome P450, family 1, subfamily A, polypeptide 2 (CYP1A2) (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A4 inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital, Gingko biloba, St. John's Wort) within 14 days before the first dose of MLN9708
  • Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure, 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
  • 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 for Adverse Events (CTCAE) grading, in the absence of antidiarrheals

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

Jacksonville, Fla.

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