SMAC Mimetic LCL161 Alone or With Cyclophosphamide in Treating Patients With Relapsed or Refractory 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:

    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: 12-010302
    • Jacksonville, Florida: 12-010302
    • Rochester, Minnesota: 12-010302
  • NCT ID:

    NCT01955434
  • Sponsor Protocol Number:

    MC1381

About this study

This phase II trial studies how well second mitochondrial-derived activator of caspases (SMAC) mimetic LCL161 alone or with cyclophosphamide works in treating patients with relapsed or refractory multiple myeloma. Biological therapies, such as SMAC mimetic LCL161, may stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving SMAC mimetic LCL161 alone or with cyclophosphamide is more effective in treating 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:

  • Relapsed or refractory multiple myeloma and has already received ≤ 4 standard treatment regimens; note: Induction, transplant, consolidation, and maintenance is considered one regimen
  • Have received prior therapy with an immunomodulatory agent, a proteosome inhibitor, and glucocorticoids
  • Absolute neutrophil count (ANC) ≥ 1000/uL
  • Untransfused platelet count ≥ 75,000/uL
  • Aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) ≤ 3 x ULN
  • Total bilirubin ≤ 1.5 mg/dL
  • Serum creatinine ≤ 2.5 mg/dL
  • Hemoglobin ≥ 8 g/dL
  • 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
    • Monoclonal plasmacytosis ≥ 30% (evaluable disease)
    • Measurable plasmacytoma that has not been radiated
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, 2
  • Willing and able to comply with scheduled visits, treatment plan and laboratory tests
  • Able to swallow and retain oral medication
  • Provide informed written consent
  • Negative serum pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only
  • Willing to provide all biological specimens as required by the protocol for correlative research purposes
  • Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
  • Mayo Clinic Arizona and Florida Only: Willing to participate in associated biobanking study, 919-04; the patient must sign consent to enroll onto the mandatory companion biobanking study in order to participate in this treatment study
  • Mayo Clinic Rochester and Florida only: Willing to participate in associated biobanking study, 521-93; the patient must sign consent to enroll onto the mandatory companion biobanking study in order to participate in this treatment study

Exclusion Criteria:

  • Prior use of investigational drugs ≤ 14 days prior to registration
  • Prior use of growth factors ≤ 14 days prior to registration
  • Prior radiation therapy ≤ 14 days prior to registration
  • Prior autologous stem cell transplant ≤ 12 weeks prior to registration
  • Any of the following:
    • Pregnant women
    • Nursing women
    • Women of childbearing potential who are unwilling to employ adequate contraception while receiving treatment on this study and for 4 months after stopping treatment on this study
    • Men who are unwilling to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while receiving treatment on this study and for 4 months after stopping treatment on this study NOTE: Postmenopausal women are allowed to participate in this study; women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in the case of oophorectomy alone, a woman is considered to be of not child bearing potential only when her reproductive status has been confirmed by follow-up hormone level assessment
  • Prior allogeneic transplant of any kind
  • Known active infection requiring parenteral or oral anti-infective treatment
  • Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse follow-up evaluation
  • Known human immunodeficiency virus (HIV) or active hepatitis B or C viral infection
  • Active autoimmune/inflammatory conditions requiring ongoing immunosuppressive therapy
  • Use of more than low dose corticosteroids (e.g., prednisone up to but no more than 10 mg PO QD or its equivalent) for symptom management and comorbid conditions, except for the following:
    • Topical applications (e.g. rash)
    • Inhaled sprays (e.g. obstructive airways diseases)
    • Eye drops or local injections (e.g. intra-articular)
    • Joint injections (e.g. arthritis) Doses of corticosteroid should be stable for at least 7 days prior to registration
  • Any concurrent severe and/or uncontrolled medical conditions that could increase the patient's risk for toxicity while in the study or that could confound discrimination between disease- and study treatment-related toxicities
  • Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
    • History or presence of ventricular tachyarrhythmia
    • Presence of unstable atrial fibrillation (ventricular response > 100 bpm) (NOTE: patients with stable atrial fibrillation are eligible, provided they do not meet any of the other cardiac exclusion criteria)
    • Clinically significant resting bradycardia (< 50 bpm)
    • Angina pectoris or acute myocardial infarction ≤ 3 months prior to registration
    • Other clinically significant heart disease (e.g., symptomatic congestive heart failure; uncontrolled arrhythmia or hypertension; history of labile hypertension or poor compliance with an antihypertensive regimen)
  • Currently receiving treatment with agents that are metabolized solely through cytochrome P450, family 3, subfamily A, polypeptide 4/5 (CYP3A4/5) and have a narrow therapeutic index or are strong cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8) inhibitors; or are receiving treatment with agents that carry a risk for QT prolongation and are CYP3A substrates; caution should be used in patients taking other CYP2C8- or CYP3A4/5-interacting agents
  • Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of LCL161

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

Leif Bergsagel, M.D.

Open for enrollment

Cancer Center Clinical Trials Referral Office

855-776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Leif Bergsagel, M.D.

Open for enrollment

Cancer Center Clinical Trials Referral Office

855-776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Leif Bergsagel, M.D.

Open for enrollment

Cancer Center Clinical Trials Referral Office

855-776-0015